MinTankesmie

- Forskning på tiltalebenken

Putting Science in the Dock (Å sette forskning på tiltalebenken)
Opinion
yahoo.com 12.3.2007 (The Nation)
The Nation -- On a chilly morning in November 2001, David Healy stood in a witness box in Kansas City, Kansas, and received a sobering lesson on the US legal system. A professor of psychological medicine at Cardiff University in Wales, Healy was an expert on serotonin, depression and the brain. He had served as secretary of the British Association for Psychopharmacology. Drug companies sought his advice. He was widely published in scientific journals. (...)

Why would a drug prevent suicide in some depressed people and potentiate it in others? One hypothesis holds that SSRIs restore a person's vigor before wiping away the depression. Perhaps patients regain the energy to kill themselves before the medicine eases their intense sadness. What's more, SSRIs upset the overall balance of chemicals in the brain, says Harvard's Glenmullen. To compensate for the serotonin boost, the level of dopamine--serotonin's chemical partner--plummets. "Whenever the drugs step on the chemical gas pedal, the brain tries to slam on the brakes," Glenmullen writes in his book Prozac Backlash. "The result is jerking, stop-and-go oscillations in brain activity that can go out of control." Dopamine suppression is associated with loss of motor control--hence the akathisia, which many researchers link directly to suicide. (...)

- Antidepressiva øker risiko for blødninger

Antidpressants raise bleeding risk in warfarin patients (Antidepressiva øker blødningsrisiko hos warfarinpasienter)
pulsetoday.co.uk 11.5.2009
Antidepressants raise the risk of clinically significant bleeding in patients on warfarin by more than three-fold, researchers warn.

Their study of 234 patients taking warfarin for atrial fibrillation found those who were also on SSRIs were at a significantly increased risk of bleeding.
Bleeding events occurred in 17 patients taking SSRIs and warfarin, but in just two on warfarin alone, with an adjusted hazard ratio of 3.5.

‘Clinically relevant bleeding occurs more frequently in warfarin-treated patients concomitantly treated with SSRI, non-gastrointestinal bleeding being the most frequent, than in those treated with warfarin alone,’ concluded the Swedish authors.

The researchers - whose study was published in the latest edition of Pharmacoepidemiology and Drug Safety – said the effect of SSRIs was unlikely to be through a direct interaction in warfarin’s anti-coagulant activity, as there was no evidence of any effect on INR scores.

‘The effect seems not to be associated with a direct influence of SSRI on the anti-coagulant activity of warfarin,’ they concluded. (...)

(Anm: Pharmacoepidemiology and Drug Safety 2009;18(5):412 – 416 (May).)

SSRIs Increase Risk of Nongastrointestinal Bleeding in Patients Taking Coumarins
medscape.com 1.2.2008
February 1, 2008 — Among users of coumarins, use of selective serotonin reuptake inhibitors (SSRIs) was linked to an increased risk for hospitalization for nongastrointestinal tract bleeding, but not gastrointestinal tract bleeding in a population-based case-control Dutch study.

These findings are published in the January 28, 2008, issue of the Archives of Internal Medicine.

"The false sentiment of safety when combining SSRIs and coumarins has been put into another perspective by our finding that the risk of other bleeding actually is increased," lead author Tom Schalekamp, PharmD, PhD, at Utrecht University, in Utrecht, the Netherlands, told Medscape Psychiatry in an email. (...)

Antidepressants Boost GI Bleeding Risk (Antidepressiva øker risiko for blødninger mage- og tarmblødning)
healthfinder.gov 12.10.2007
And the danger rises if the drugs are used with certain painkillers, study finds
(SOURCE: Wake Forest University Baptist Medical Center, news release, Oct. 8, 2007)

FRIDAY, Oct. 12 (HealthDay News) -- Antidepressant drugs called selective serotonin reuptake inhibitors (SSRIs), which include Celexa, Paxil, Prozac and Zoloft, can double the risk of gastrointestinal bleeding, and the threat is more than six times higher if patients take aspirin and similar pain medications at the same time as SSRIs, a new study finds.

"Clinicians who prescribe these medications should be aware of the potential risk and may need to consider alternatives," senior researcher Dr. Sonal Singh, assistant professor of internal medicine at Wake Forest University School of Medicine, in Winston-Salem, N.C., said in a prepared statement.

His team published the findings in the journal Alimentary Pharmacology & Therapeutics.

In addition to depression, SSRIs are also used to treat panic disorder and obsessive-compulsive disorder. There's growing evidence that SSRIs may be associated with upper gastrointestinal (GI) bleeding.

Singh and colleagues analyzed data from four studies involving 153,000 patients. They found that those taking SSRIs were nearly twice as likely to develop upper GI bleeding as people who weren't taking the drugs. (...)

(Anm: Akutt mage- og tarmblødning. Er behandlingstilbudet godt nok? Tidsskr Nor Lægeforen 1996; 116: 1659.)

(Anm: Acetylsalisylsyre (Acetylsalicylic Acid). Stoffet brukes mot smerter og feber og finnes under flere varemerkebeskyttede navn, blant annet Dispril, Aspirin og Globoid.(no.wikipedia.org).)

(Anm: Risk of Upper Gastrointestinal Bleeding With Low-Dose Acetylsalicylic Acid Alone and in Combination With Clopidogrel and Other Medications.Circulation. 2011;123:1108-1115 (March 15).)

- Graviditetsrelaterte hjerneslag øker

Pregnancy-Related Strokes on the Rise (Graviditetsrelaterte hjerneslag øker)
JAMA 2011 (July 28)
More women are experiencing strokes during pregnancy or shortly after delivery, according to a study published today in the journal Stroke.

The researchers used data from the Nationwide Inpatient Sample, the largest collection of nationwide data on hospitalizations, to compare pregnancy-related strokes in women during 2 periods: in 1994-1995 and 2006-2007. They found that although the rate of hospitalization for stroke during delivery stayed steady, the rate of hospitalization for stroke during pregnancy increased by 47% (from 0.15 to 0.22 per 1000 deliveries) and by 83% after delivery during the 12-week postpartum period (from 0.12 to 0.22 per 1000 deliveries).

Most of the increase in pregnancy-related strokes can be explained by increased rates of hypertension and heart disease among pregnant women, according to the authors. Changes in demographics, such as more women having children later in life, and improvements in medical care for women with chronic conditions, such as congential heart disease or autoimmune disorders, may explain why more women are beginning their pregnancies with cardiovascular risk factors, they note. (...)

(Anm: Trends in Pregnancy Hospitalizations That Included a Stroke in the United States From 1994 to 2007. Stroke 2011 (Published online before print July 28).)

- Større risiko for tilbakefall hos pasienter som bruker antidepressiva

Greater Risk Of Relapse In Patients Who Use Anti-Depressants (Større risiko for tilbakefall hos pasienter som bruker antidepressiva)
medicalnewstoday.com 20.7.2011
Pasienter som bruker antidepressiva er mye mer sannsynlig å lide av tilbakefall av kraftig depresjon enn de som ikke bruker legemidler i det hele tatt, konkluderer McMaster-forsker. (Patients who use anti-depressants are much more likely to relapses of major depression than those who use no medication at all, concludes a McMaster researcher.)

In a paper that is likely to ignite new controversy in the hotly debated field of depression and medication, evolutionary psychologist Paul Andrews concludes that patients who have used anti-depressant medications can be nearly twice as susceptible to future episodes of major depression.

Andrews, an assistant professor in the Department of Psychology, Neuroscience & Behaviour, is the lead author of a new paper in the journal Frontiers of Psychology. (...)

(Anm: Blue again: perturbational effects of antidepressants suggest monoaminergic homeostasis in major depression. Front. Psychology 2011;2:159 (Published online: 07 July 2011).)

- Bevis for kronisk endrede serotoninfunksjon i hjernebarken (cerebral cortex) hos kvinnelige polysubstansbrukere av Methylenedioxymethamphetamine (MDMA, Ecstasy)

Evidence for Chronically Altered Serotonin Function in the Cerebral Cortex of Female 3,4-Methylenedioxymethamphetamine Polydrug Users (Bevis for kronisk endrede serotoninfunksjon i hjernebarken (cerebral cortex) hos kvinnelige polysubstansbrukere av Methylenedioxymethamphetamine)
Arch Gen Psychiatry. 2012;69(4):399-409 (April)
Context MDMA (3,4-methylenedioxymethamphetamine, also popularly known as "ecstasy") is a popular recreational drug that produces loss of serotonin axons in animal models. Whether MDMA produces chronic reductions in serotonin signaling in humans remains controversial.

Objective To determine whether MDMA use is associated with chronic reductions in serotonin signaling in the cerebral cortex of women as reflected by increased serotonin2A receptor levels.

Design Cross-sectional case-control study comparing serotonin2A receptor levels in abstinent female MDMA polydrug users with those in women who did not use MDMA (within-group design assessing the association of lifetime MDMA use and serotonin2A receptors). Case participants were abstinent from MDMA use for at least 90 days as verified by analysis of hair samples. The serotonin2A receptor levels in the cerebral cortex were determined using serotonin2A-specific positron emission tomography with radioligand fluorine 18–labeled setoperone as the tracer.

Setting Academic medical center research laboratory.

Participants A total of 14 female MDMA users and 10 women who did not use MDMA (controls). The main exclusion criteria were nondrug-related DSM-IV Axis I psychiatric disorders and general medical illness.

Main Outcome Measures Cortical serotonin2A receptor nondisplaceable binding potential (serotonin2ABPND).

Results MDMA users had increased serotonin2ABPND in occipital-parietal (19.7%), temporal (20.5%), occipitotemporal-parietal (18.3%), frontal (16.6%), and frontoparietal (18.5%) regions (corrected P < .05). Lifetime MDMA use was positively associated with serotonin2ABPND in frontoparietal (β = 0.665; P = .007), occipitotemporal (β = 0.798; P = .002), frontolimbic (β = 0.634; P = .02), and frontal (β = 0.691; P = .008) regions. In contrast, there were no regions in which MDMA use was inversely associated with receptor levels. There were no statistically significant effects of the duration of MDMA abstinence on serotonin2ABPND.

Conclusions The recreational use of MDMA is associated with long-lasting increases in serotonin2A receptor density. Serotonin2A receptor levels correlate positively with lifetime MDMA use and do not decrease with abstinence. These results suggest that MDMA use produces chronic serotonin neurotoxicity in humans. Given the broad role of serotonin in human brain function, the possibility for therapeutic MDMA use, and the widespread recreational popularity of this drug, these results have critical public health implications. (...)

(Anm: Hjernebarken, cerebral cortex, cortex cerebri eller bare cortex er det ytre laget av storehjernen, en del av hjernen som finnes hos alle virveldyr, også mennesker. (no.wikipedia.org).)

(Anm: MDMA (3,4-metylendioksymetamfetamin) er et forskningsmedikament for behandling av angstlidelser, og virkestoffet i partydopet ecstasy. (...) Andre navn på ecstasy brukt i Norge er «E», «Bokstaver», «Knips» eller andre navn etter symbolet på tablettene. (no.wikipedia.org).)

- Pfizers Zyvoxid (Zyvox) og antidepressiva kan være en dødelig kombinasjon

FDA Warns About Nervous System Reactions from Zyvox, Methylene Blue (FDA advarer om reaksjoner i nervesystemet fra Zyvoxid (Zyvox), Methylene Blue)
aboutlawsuits.com 27.7.2011
Federal drug regulators are warning that there is a risk of serious central nervous system reactions when the drugs Zyvox and methylene blue are used with some antidepressants, including Paxil, Zoloft, Prozac and Cymbalta, among many others.

The FDA issued a drug safety communications for methylene blue and Zyvox on Tuesday, indicating that the agency analyzed adverse event reports that included reports of central nervous system (CNS) toxicity and some deaths. The reactions were due to drug interactions between the two drugs and psychiatric medications that affect the serotonin system of the brain, according to the FDA warning.

Methylene blue and Zyvox are both reversible monoamine oxidase inhibitors (MAOI). Methylene blue is used to treat cyanide poisoning, methemoglobinemia, vasoplegic syndrome and ifosfamide-induced encephalopathy. It is also used as a dye in therapeutic and diagnostic applications. Zyvox (linezolid) is used to treat infections, including pneumonia, skin infections and methicillin-resistant Staphylococcus aureus (MRSA).

The FDA warning includes a full list of serotonergic psychiatric medications that could react with the drugs. The list includes selective serotonin reuptake inhibitors (SSRIs), which are the most common psychiatric drugs on the market, as well as tricyclic antidepressants, serotonin-norepinephrine reuptake inhibitors (SNRIs) and other MAOIs and psychiatric drugs. The list includes some of the most prescribed drugs in the world, such as Paxil, Prozac, Zoloft, Celexa, Lexapro, Effexor, Cymbalta, Wellbutrin and Zyban.

Why the interaction between the drugs causes CNS toxicity is unknown, but the FDA states that some experts believe that the Zyvox and methylene blue cause high levels of serotonin to build up in the brain when used with the serotonergic drugs, resulting in toxicity. This is known as serotonin syndrome and can cause confusion, hyperactivity, memory loss, muscle twitching, excessive sweating, shivering and shaking, diarrhea, fever and trouble with coordination.

The agency is recommending that patients prescribed methylene blue and Zyvox should be taken off of any of the listed antidepressants two weeks prior. However, in some cases the drugs are given as an emergency treatment. In those instances, doctors should attempt to find an alternative method of treatment, the FDA recommended.

The antidepressants can be resumed 24 hours after the last dose of methylene blue and Zyvox, the FDA stated.

(Anm: linezolid (antibiotika; Zyvox i USA); Zyvoxid (in Europe), and Zyvoxam (in Canada and Mexico). Generics are also available in India, such as Linospan (Cipla). (en.wikipedia.org).)

(Anm: Serotonin syndrom (SS), kramper, parkinsonisme osv. (forhøyet kroppstemperatur) (mintankesmie.no).)

(Anm: Seroxat (Paxil) (paroxetine; paroksetin) (SSRI) (mintankesmie.no).)

Pfizer's Zyvox and Antidepressants May Be Fatal Combination (Pfizers Zyvoxid (Zyvox) og antidepressiva kan være en dødelig kombinasjon)
sfgate.com 26.7.2011
July 26 (Bloomberg) -- Pfizer Inc.'s Zyvox antibiotic can cause potentially fatal central nervous system reactions in patients who also take antidepressants that increase levels of the brain chemical serotonin, U.S. regulators said.

Pfizer's Zoloft and Pristiq, Eli Lilly & Co.'s Cymbalta and GlaxoSmithKline Plc's Paxil and Wellbutrin are among 29 psychiatric drugs that patients may need to stop taking temporarily when they require treatment with Zyvox, the Food and Drug Administration said today in a drug safety communication.

Zyvox, used to treat some types of drug-resistant bacteria including MSRA or methicillin-related Staphylococcus aureus, skin infections and nosocomial pneumonia, can interact with the antidepressants to cause a toxic reaction known as serotonin syndrome in which excess amounts of the chemical build up in the brain, according to the FDA.

Some deaths among patients who suffered such a reaction were reported to the FDA's adverse-event database, the agency said. Pfizer, based in New York, reported $1.18 billion in revenue from Zyvox last year. (...)

(Anm: linezolid (antibiotika; Zyvox i USA); Zyvoxid (in Europe), and Zyvoxam (in Canada and Mexico). Generics are also available in India, such as Linospan (Cipla). (en.wikipedia.org).)

FDA Warns of Serious Drug Interactions in Patients Taking Psychiatric Drugs (FDA advarer mot alvorlige interaksjoner hos pasienter som tar psykiatriske legemidler)
JAMA 2011 (July 27)
Patients taking certain psychiatric drugs may experience serious neurological problems if they are given the antibacterial medication linezolid (sold under the brand name Zyvox) or methylene blue, a drug that is also used as a dye in some diagnostic procedures and for certain other uses, such as treating cyanide poisoning, according to a pair of warnings issued yesterday by the US Food and Drug Administration (FDA).

The warning applies to psychiatric drugs that affect the brain’s serotonin system and includes those used to treat depression such as selective serotonin reuptake inhibitors, serotonin-norepinephrine reuptake inhibitors, tricyclic antidepressants, monoamine oxidase inhibitors, and certain other psychiatric drugs. A full list of these drugs is available on the FDA’s Web site. (...)

(Anm: linezolid (antibiotika; Zyvox i USA); Zyvoxid (in Europe), and Zyvoxam (in Canada and Mexico). Generics are also available in India, such as Linospan (Cipla). (en.wikipedia.org).)

Zyvox (linezolid): Drug Safety Communication - Serious CNS Reactions Possible When Given to Patients Taking Certain Psychiatric Medications (Zyvox (linezolid): Sikkerhetskommunikasjon legemidler - Alvorlige CNS-reaksjoner mulig når det gis pasienter som inntar visse psykiatriske legemidler)
fda.gov 26.7.2011
ISSUE: FDA has received reports of serious central nervous system (CNS) reactions when the antibacterial drug linezolid (Zyvox) is given to patients taking psychiatric medications that work through the serotonin system of the brain (serotonergic psychiatric medications. A list of the serotonergic psychiatric medications that can interact with linezolid can be found in the Drug Safety Communication. Safety information about this potential drug interaction and important drug usage recommendations for emergency and non-emergency situations are being added to the drug labels for serotonergic psychiatric medications and linezolid. (...)

RECOMMENDATION: Linezolid should generally not be given to patients taking serotonergic drugs. However, there are some conditions that may be life-threatening or require urgent treatment with linezolid such as when:

• Linezolid is used to treat vancomycin-resistant Enterococcus faecium (VRE) infections.
• Linezolid is used to treat infections such as nosocomial pneumonia and complicated skin and skin structure infections, including cases caused by methicillin-resistant Staphylococcus aureus (MRSA).

Patients should not stop taking their serotonergic psychiatric medicine without first talking to a healthcare professional. Read the Drug Safety Communication for other specific recommendations for Healthcare Professionals and for Patients. (...)

(Anm: linezolid (antibiotika; Zyvox i USA); Zyvoxid (in Europe), and Zyvoxam (in Canada and Mexico). Generics are also available in India, such as Linospan (Cipla). (en.wikipedia.org).)

Methylene Blue: Drug Safety Communication - Serious CNS Reactions Possible When Given to Patients Taking Certain Psychiatric Medications
fda.gov 26.7.2011
ISSUE: FDA has received reports of serious central nervous system (CNS) reactions when the drug methylene blue is given to patients taking psychiatric medications that work through the serotonin system of the brain (serotonergic psychiatric medications). A list of the serotonergic psychiatric medications that can interact with methylene blue can be found in the Drug Safety Communication. Safety information about this potential drug interaction and important drug usage recommendations for emergency and non-emergency situations are being added to the drug labels for serotonergic psychiatric medications. (...)

RECOMMENDATION: Methylene blue should generally not be given to patients taking serotonergic drugs. However, there are some conditions that may be life-threatening or require urgent treatment with methylene blue such as when it is used in the emergency treatment of methemoglobinemia, ifosfamide-induced encephalopathy, or cyanide poisoning.

Patients should not stop taking their serotonergic psychiatric medicine without first talking to a healthcare professional. Read the Drug Safety Communication below for other specific recommendations for Healthcare Professionals and for Patients. (...)

FDA: Avoid Methylene Blue or Linezolid With Serotonergics
medscape.com 26.7.2011
July 26, 2011 — Physicians generally should avoid prescribing either methylene blue or linezolid (Zyvox,Pfizer) in combination with serotonergic agents such as paroxetine or duloxetine to avoid a potential drug interaction causing a dangerous condition called serotonin syndrome, the US Food and Drug Administration (FDA) announced today.

Linezolid is an antibacterial agent, and methylene blue is a dye used in diagnostic procedures and in the treatment of conditions ranging from methemoglobinemia to cyanide poisoning.

Through its Adverse Event Reporting System (AERS) database, the FDA has learned of serious central nervous system reactions when either drug has been given to patients taking other drugs that work through the serotonin system of the brain. (...)

- Dyskinesi linket til serotonin

Some PD Dyskinesia Linked to Serotonin (Dyskinesi linket til serotonin hos enkelte med parkinsons sykdom (PD))
medpagetoday.com 30.6.2010
Fetal tissue transplants for Parkinson's disease initially seemed promising, but after a period of improvement, most patients began experiencing involuntary movements. Now British and Swedish researchers think they've worked out the paradoxical cause of that so-called "graft-induced dyskinesia" and in the process identified ways to prevent and treat it, according to Marios Politis, MD, of Imperial College London, and colleagues.

The key is an excess of serotonin-producing neurons in the grafted striatum, Politis and colleagues said in the June 30 issue of Science Translational Medicine.

Dyskinesias in Parkinson's disease are thought to be a result of dopamine, not serotonin, stimulation, but the graft-induced dyskinesias occur in the absence of dopaminergic medication. Politis and colleagues thought that the explanation might lie in the ability of the serotonin neurons to switch to a different neurotransmitter -- to use dopamine as a so-called "false transmitter."

To test the idea, they used brain imaging techniques on two patients who had been given fetal tissue transplants, 12 Parkinson's patients who had not been transplanted, and 12 healthy volunteers.

Positron emission tomography radioactive tracers that bind to dopaminergic neurons and to the dopamine receptor showed that, in the two patients, the grafts had restored the dopamine neurons that decay during Parkinson's disease.

In both patients, the neurons and the amount of dopamine they released returned to normal values after the transplant, Politis and colleagues found.

But in both, there were more serotonin neurons than usual. Specifically:

•In one patient, the ratio of serotonin to dopamine neurons in the grafted region increased by a factor of 2.3 compared with the ratio in normal controls -- at 356 versus 108.
•In the second patient, the ratio was also increased, by a factor of 1.46 -- at 266 versus 108.

The findings suggested that blocking the action of the serotonin neurons might improve the symptoms, Politis and colleagues said. To test the idea, they treated both patients with 15 milligrams of the 5-HT1A agonist buspirone (BuSpar), given in three doses of five milligrams at 30-minute intervals.(...)

(Anm: dyskinesi; dyskinesi. (av dys- og gr. 'sette i bevegelse'), forstyrrede kroppsbevegelser. (...) mer eller mindre permanent art, oftest ved langvarig bruk av nevroleptika. (...) Typisk er stereotype, rytmiske bevegelser i ansikt, tunge og kjevemuskulatur. En viss samtidig muskulær urofølelse kan forekomme (akathisi). Kilde: Store norske leksikon.)

(Anm: akatisi; manglende evne til å sitte stille, sterk rastløshet og trang til å vandre rundt. Akatisi skyldes oftest utilsiktede og uønskede forandringer i sentralnervesystemets funksjon. De er fremkalt av medisiner og er bivirkninger. Akatisi er oftest fremkalt av nevroleptika, spesielt såkalte lavdosenevroleptika, vanligvis ved behandling av alvorlige psykiske lidelser (se psykose). Kilde: Store norske leksikon.)

(Anm: dystonia; dystoni; endring i muskulaturens spenningstilstand, ofte i form av ufrivillige muskelsammentrekninger (f.eks. i nakkemuskulaturen og svelgmuskulaturen. Dystoni kan være symptom ved indremedisinske og nevrologiske sykdommer, men kan også opptre som bivirkning av legemidler som blokkerer signalsubstansen dopamin. Akutte dystonier sees hos yngre menn noen dager etter at vedkommende har begynt på relativt høye doser med nevroleptika. (...) Ved akutte dystonier på grunn av legemidler er behandlingen tilførsel av antiparkinsonmidler. Kilde: Store norske leksikon.)

- Seroxat-dødsfall grunnet serotonin syndrom og hypertermi (forhøyet kroppstemperatur)

Justice for his brother David (Retterdighet for hans bror Daivid)
bellinghamherald.com 25.10.2010
David Vernon was one of society’s most vulnerable individuals, completely dependent on others for the simplest care. (...)

A caregiver for Aacres LLC found him unresponsive on his bedroom floor just before 5 a.m. A reading later taken at St. Joseph Medical Center – where Vernon was taken by ambulance – showed his temperature to be 107 degrees.

The Mayo Clinic recommends people with a temperature of 104 seek immediate medical attention.

The Pierce County Medical Examiner’s Office ruled David Vernon’s death an accident, and at least three other investigations into his death placed no blame on Aacres. (...)

They also reported that he had not complained of being hot or shown signs of heat exhaustion on July 28.

På det tidspunkt han døde, tok Vernon to forskrevne reseptbelagte legemidler mot psykiske lidelser: olanzapine (Zyprexa) og paroxetine (Seroxat). Olanzapine er brukt mot skizofreni; paroxetine er brukt mot depresjon og andre stemningslidelser. (At the time of his death, Vernon was taking two drugs prescribed to treat his mental illness: olanzapine and paroxetine. Olanzapine is used to treat schizophrenia; paroxetine is given to treat depression and other mood disorders.)

Begge kan ganger noen medføre hypertermi. (Both can make someone taking them prone to hyperthermia.)

“You should know that olanzapine may make it harder for your body to cool down when it gets very hot,” according to a brochure about the drug published by American Society for Health-System Pharmacists. “Tell your doctor if you plan to do vigorous exercise or be exposed to extreme heat.”

Seroxat (paroxetine) er kjent for å forårsake serotonin syndrom, et potensielt dødelig syndrom som kan opptre hos mennesker som tar disse terapeutiske legemidler. Hvilket kan resultere i hyperthermi. (Paroxetine is known to cause serotonin syndrome, a potentially deadly reaction that can occur in people taking certain therapeutic drugs. Hyperthermia can result.)

“Symptomer kommer vanligvis raskt, med kliniske funn som ofte opptrer innen minutter etter endring i medisinering eller overdosering,” ifølge en studie på syndromet publisert i The New England Journal of Medicine den 17. mars 2005. “Pasienter med milde tegn kan ha subakutte eller kroniske symptomer, mens alvorlige tilfeller raskt kan føre til dødsfall.” (“The onset of symptoms is usually rapid, with clinical findings often occurring within minutes after a change in medication or self-poisoning,” according to a study on the syndrome published in the March 17, 2005, issue of The New England Journal of Medicine. “Patients with mild manifestations may present with subacute or chronic symptoms, whereas severe cases may progress rapidly to death.”)

Symptomer på syndromet er vanskelig å oppdage og ofte oversett av leger, ifølge artikkelen, som også påpeker at en eneste dose av paroxetine er nok til å forårsake tilstanden. Dødsfall grunnet syndromet er sjelden ifølge medisinsk literatur. (Symptoms of the syndrome are tough to spot and often missed by physicians, according to the article, which also points out that a single dose of paroxetine is enough to cause the condition. Death from the syndrome is rare, according to medical literature.)

Laboratory tests found unusually high levels of paroxetine – more than 16 times normal levels – in Vernon’s blood at the time of his death, according to the medical examiner’s report. He was taking 50 milligrams of paroxetine each night before bedtime, according to DSHS records.

It was unknown how Vernon – who was about 5 feet 7 and 180 pounds – built up such a high level of the drug in his system. (...)

(Anm: paroksetin (paroxetine); markesføres i Norge under handelsnavn som bl.a. Seroxat; Paxil i USA.)

(Anm: Serotonin syndrom (SS), kramper, parkinsonisme osv. (forhøyet kroppstemperatur) (mintankesmie.no).)

(Anm: hypertermi, forhøyet kroppstemperatur (over 38,2 °C) som en følge av at organismens varmeproduksjon øker mer enn varmetapet. Kilde: Store norske leksikon.)

- Krybbedød (SIDS - Sudden Infant Death Syndrome - krybbedød)

Serotoninbrist kopplas till plötslig spädbarnsdöd
dagensmedicin.se 4.2.2010
Barn som dött i plötslig spädbarnsdöd har lägre nivåer av serotonin i hjärnstammen, enligt en ny studie.

Plötslig spädbarnsdöd, SIDS, antas bero på problem med hjärnstammens reglering av andning och autonoma funktioner. Det har tidigare rapporterats om serotoninreceptorer i förlängda märgen, den nedre delen av hjärnstammen, som binder på ett onormalt sätt hos barn som avlidit i plötslig spädbarnsdöd. (...)

Serotonin May Be Key to Sudden Infant Deaths (Serotonin kan være nøkkel til krybbedød)
health.msn.com 2.2.2010
Deficiency hampers babies' ability to respond to low oxygen, study suggests
TUESDAY, Feb. 2 (HealthDay News) -- Lack of the brain chemical serotonin may be crucial to sudden infant death syndrome (SIDS), new research finds.

Babies who died of SIDS had significantly lower levels of serotonin -- an important regulator of involuntary functions such as breathing and heart rate -- compared to babies who died of other causes, the study found. This finding may eventually lead to a test that could screen newborns to spot those most vulnerable to SIDS.

"This study is confirming that SIDS is a serotonin problem, and we're getting closer to the fundamental mechanism behind SIDS," said the study's senior author, Dr. Hannah C. Kinney, a neuropathologist at Children's Hospital Boston and a professor of pathology at Harvard Medical School.

"The goal is to develop a test to identify which babies are at risk, and then to find a drug that might be able to help them through the critical period. But these are long-term goals," she said.

Results of the study are published in the Feb. 3 issue of the Journal of the American Medical Association. (...)

In the current study, Kinney and her colleagues measured levels of serotonin and trytophan hydroxylase (TPH2) in 35 babies who died from SIDS and in 12 babies who died of other, known causes. TPH2 is an enzyme that helps make serotonin. In the group of babies who had died of other causes, the researchers included infants who had experienced oxygen deprivation near death to rule that factor out as a cause of lower serotonin levels. (...)

(Anm: Brainstem Serotonergic Deficiency in Sudden Infant Death Syndrome. JAMA. 2010;303(5):430-437 (February 3).)

Low production of serotonin in the brainstem a likely cause for SIDS (Lav produksjon av serotonin i hjernesatammen sannsynlig årsak til SIDS)
eurekalert.org 2.2.2010
Doctors closing in on mysterious cause of death in infants
Boston, Mass. – Taking the next step in more than 20 years of research, researchers at Children's Hospital Boston have linked sudden infant death syndrome (SIDS) with low production of serotonin in the brainstem, based on a comparison of brainstem samples from infants dying of SIDS compared to brainstems of infants dying from other, known causes.

The findings, published in the Feb. 3 issue of The Journal of the American Medical Association, may give a concrete approach to identifying babies at risk for SIDS, the leading cause of death for infants between 1 and 12 months old in the United States.

In the brainstem, serotonin helps regulate some of the body's involuntary actions, such as breathing, heart rate and blood pressure during sleep. The researchers, led by Children's neuropathologist Hannah Kinney, MD, believe that a low serotonin level impairs the function of the brainstem circuits that regulate these activities, putting a baby at risk for sudden death from stresses such as rebreathing carbon dioxide when sleeping in the face down position. (...)

Low Serotonin Eyed as Mechanism for SIDS
medpagetoday.com 2.2.2010
Low brainstem levels of serotonin and the enzyme that makes it could underlie sudden infant death syndrome (SIDS), researchers suggested. (...)

Brainstem Serotonergic Deficiency in Sudden Infant Death Syndrome
JAMA. 2010;303(5):430-437 (February 3)
Context Sudden infant death syndrome (SIDS) is postulated to result from abnormalities in brainstem control of autonomic function and breathing during a critical developmental period. Abnormalities of serotonin (5-hydroxytryptamine [5-HT]) receptor binding in regions of the medulla oblongata involved in this control have been reported in infants dying from SIDS. (...)

Conclusion Compared with controls, SIDS was associated with lower 5-HT and TPH2 levels, consistent with a disorder of medullary 5-HT deficiency. (...)

Fan Use Near Sleeping Infant May Protect Against SIDS
medpagetoday.com 6.10.2008
OAKLAND, Calif., Oct. 6 -- To decrease the risk of sudden infant death syndrome (SIDS), parents may want to use a fan to circulate the air around a sleeping baby, a case-control study suggested. (...)

(Anm: Use of a Fan During Sleep and the Risk of Sudden Infant Death Syndrome. Arch Pediatr Adolesc Med. 2008;162(10):963-968.)

Serotonin Dysfunction Causes SIDS -Like Deaths in Mouse Pups (Serotonerg dysfunksjon forårsaker SIDS-liknende dødsfall hos museunger)
medpagetoday.com 3.7.2008
MONTEROTONDO, Italy, July 3 -- Baby mice engineered to have defective serotonin regulation unexpectedly died with what looked much like sudden infant death syndrome, researchers here said.

In mice overexpressing serotonin 1A autoreceptors in their brainstems, most died while still pups with signs of hypothermia and bradycardia, along with other abnormalities in autonomic functions strongly reminiscent of SIDS, reported Cornelius Gross, Ph.D., of the European Molecular Biology Laboratory, and colleagues in the July 4 issue of Science.

The serotonin 1A receptors are part of a negative feedback loop controlling both the amount of serotonin released into nerve synapses as well as the sensitivity to serotonin signaling. (...)

The murine study supports earlier research suggesting that defects in the serotonin pathway are at the root of human SIDS. (See: Serotonin Defects Said to Underlie SIDS)

In the current study, 70% of the animals died before they were 120 days old, with death most frequently occurring from days 25 to 80 after birth. The animals showed sporadic episodes of hypothermia and slow heartbeat, an effect seen in a small number of human babies monitored during SIDS events. (...)

Chance discovery points to crib death cause
reuters.com 3.7.2008
LONDON (Reuters) - An imbalance of a key brain chemical could cause crib death, researchers said on Thursday in what they called a chance discovery.
They created mice whose sudden deaths resembled crib death in humans, and found that the key may be an out of balance self-regulating system controlling the nerve-signalling chemical serotonin.

Writing in the journal Science, they said they hoped their experiment can help doctors pinpoint human babies at high risk of Sudden Infant Death Syndrome (SIDS), also known as cot death.

"At first sight the mice were normal," said Cornelius Gross of the European Molecular Biology Laboratory in Italy, who led the study.

"But then they suffered sporadic and unpredictable drops in heart rate and body temperature. More than half of the mice eventually died of these crises during a restricted period of early life. It was at that point that we thought it might have something to do with SIDS." (...)

Genetically engineered mice whose self-regulating serotonin system was turned off did not die, showing it was worse to have a malfunctioning system than no system at all, he added.

"We have actually shown you can introduce changes in the serotonin system and they can cause death," Gross said.

Serotonin neurons in the brainstem -- the part of the brain that controls breathing and other unconscious functions -- do not work properly in the gene-engineered mice. (...)

Central serotonin pathways implicated in sudden infant deaths
BMJ 2006;333:1013-1014 (11 November)
Central serotonin pathways implicated in sudden infant deaths

The exact cause of sudden infant death syndrome (SIDS) is unknown. But evidence is mounting that the defect lies somewhere within the serotonergic pathways of the medulla oblongata. (...)

Serotonin dreams
timesonline.co.uk 4.11.2006
It’s too soon to say if the brain chemical is a clue to cot death (...)

The drugs known as selective serotonin re-uptake inhibitors (SSRIs) such as Prozac work by keeping serotonin washing about in the brain for longer, thereby correcting the imbalance said to cause mood disorders. Drug companies argue that because these can be effective, lack of serotonin is the root of depression. But, actually, that’s a backwards argument, like saying that if Aspirin cures headache, there must be a deficiency of it in the brain. (...)

Study links SIDS to brain chemical defect
latimes.com 4.11.2006
In a small study with big implications, researchers found some of the strongest evidence yet that sudden infant death syndrome — a medical and sometimes legal mystery once known as crib death — may be caused by abnormalities in the brain stem. (...)

The brain-stem abnormalities involve an imbalance in the way the brain uses the neurotransmitter serotonin. The brain chemical, which plays a role in regulating mood and is the target for many depression-fighting drugs, also influences breathing, body temperature and arousal from sleep.

These functions are thought to go awry when susceptible babies are exposed to certain risks, such as sleeping on their bellies, a leading contributor to SIDS.

The researchers, who published their findings Wednesday in the Journal of the American Medical Assn., studied autopsied brain tissue from 31 SIDS babies and 10 infants who died of other causes. SIDS babies had about double the number of nerve cells displaying serotonin defects. (...)

Krybbedød-gåten kan være løst
dagbladet.no 1.11.2006
(...) Det har lenge vært kjent at risikoen for krybbedød øker når barnet sover på magen eller i sideleie, men forskerne har ikke klart å finne ut av hvorfor det er slik. En ny amerikansk studie kan vise seg å være et gjennombrudd i å løse gåten. (...)

Sudden Infant Death Syndrome
Is Serotonin the Key Factor?
JAMA. 2006;296:2143-2144.
Neuropathological studies have identified a key role for the serotonin (5-hydroxytryptamine [5-HT]) pathways in sudden infant death syndrome (SIDS). Panigrahy et al1 reported a decrease in 5-HT receptor binding in the arcuate nucleus, raphé obscurus, and other medullary regions that contain 5-HT cell bodies in SIDS cases in the United States. Similarly, Ozawa and Okado2 reported a decrease in 5-HT receptor binding in the dorsal nucleus of the vagus, solitary nucleus, and ventrolateral medulla in SIDS cases in Japan. Subsequently, Kinney et al3 confirmed their prior observations of altered 5-HT receptor binding in medullary regions in Native American Indians, a group at high risk for SIDS. (...)

Serotonin Levels Tied to SIDS
healthfinder.gov 8.3.2006
Infants can't gasp and wake themselves up, researchers speculate.
-- While the exact cause of SIDS is unknown, a new study provides what researchers hope will be an important clue that could lead to screening, and perhaps new treatments, for the deadly syndrome.

In work done with brain stems from mice, researchers found out what happens when the brain's level of oxygen is depleted and the levels of the hormone serotonin are disturbed in so-called pacemaker cells.

These cells are a specific group of neurons that these same researchers have already shown to be responsible for gasping, which is needed to reset a normal breathing pattern in sleeping babies.

The researchers found that normal serotonin levels are needed for these respiratory pacemakers to induce gasping. It has been found that infants who die from SIDS -- sudden infant death syndrome -- have disturbed levels of serotonin. About 3,000 infants die each year from SIDS, and it is the primary cause of death for those under the age of 1, according to the U.S. Centers for Disease Control and Prevention.

The new report appears in the March 8 issue of the Journal of Neuroscience.
"When you have no oxygen, you shut down your respiratory network," explained study author Jan-Marino Ramirez, an associate professor of organismal biology and anatomy at the University of Chicago. "You rely on gasping as the only chance to wake up."

Others have shown that, with SIDS, infants gasp only one or two times and they don't wake up, Ramirez said. "We have shown that the nerve cells that you need for gasping need serotonin," he said. (...)

- Infants born to women who had taken SSRIs after the 20th week of pregnancy experienced a sixfold increase in the risk of persistent pulmonary hypertension of the newborn (PPHN)

New Studies on Antidepressants in Pregnancy Recalls and Safety Alerts
fda.gov (November 2006)
In a recent Public Health Advisory, FDA summarized two new studies that practitioners should consider when making decisions about prescribing SSRIs and other antidepressant medications for pregnant women and those planning a pregnancy.

The first study followed pregnant women with a history of depression who had been taking antidepressants before they got pregnant. Those who stopped their medications were five times more likely to experience a relapse of depression during their pregnancy than those who continued to take the drugs.

FDA's Advisory recommends that women who are pregnant or considering pregnancy not discontinue their antidepressants without consulting their physician. If the medication is stopped, patients should be monitored closely for signs of a relapse.

The second study found that infants born to women who had taken SSRIs after the 20th week of pregnancy experienced a sixfold increase in the risk of persistent pulmonary hypertension of the newborn (PPHN). PPHN is a life-threatening condition that becomes evident soon after birth and occurs in one to two per thousand births in the U.S. Infants with PPHN become hypoxemic because of abnormal blood flow through the heart and lungs.

This link between SSRIs and PPHN has not been investigated in other studies, and FDA is seeking more information about the possible risk of PPHN in infants born to mothers who took antidepressants during pregnancy. In the meantime, FDA has asked the manufacturers of all SSRIs to add the potential risk of PPHN to their prescribing information.

The possible risk of PPHN adds to concerns raised in other reports that infants of mothers who take antidepressants late in pregnancy may experience problems such as irritability, difficulty in feeding, and in rare cases, difficulty in breathing. And the labeling for Paxil (paroxetine hydrochloride) now cautions that exposure during the first trimester could be associated with an increased risk of cardiac anomalies in the newborn. (...)

(Anm: pulmonal hypertensjon; for høgt blodtrykk i lungepulsåra – arteria pulmonalis, kan gi tung pust ved pårøyning, brystsmerter, synkopetendens m v; kan skuldast mitralstenose eller andre slags, gjerne medfødde hjartesjukdommar, lungeemboliar (ev i form av kronisk tromboembolisk pulmonal hypertensjon), visse medikament (jf aminorex, fenfluramin), kollagene åresjukdommar m v; jf primær pulmonal hypertensjon og endotelin 1
EN pulmonary hypertension. Kilde: Norsk medisinsk ordbok.)

- Serotonin involved in early embryo patterning, Forsyth scientists find

Serotonin involved in early embryo patterning, Forsyth scientists find
medicalnewstoday.com 10.5.2005
The scientists also found that serotonin plays a key role in determining where organs are positioned in the body during embryonic development.

The study, published in the May 10 Current Biology, has ramifications for neuroscience, developmental genetics, evolutionary biology and, possibly, human teratology (a branch of pathology and embryology concerned with abnormal development and congenital malformations).

Among other results, the study, which was carried out on frog and chick embryos:

-- Provides the first molecular support for the idea that serotonin is utilized as a large-scale left-right patterning mechanism, thus offering new insight into the basis of position of the heart and other asymmetric, visceral organs.

-- Identifies a possible novel serotonin signaling pathway, providing evidence that serotonin can signal inside the cell. If also found in mammals, such signaling, which may be important in brain functioning, would suggest numerous new roles and possible targets for serotonin-related drugs like the selective serotonin reuptake inhibitors (SSRI antidepressants such as Prozac and Zoloft) or the monoamine oxidase inhibitors (MAOIs).

-- Could lead to a greater understanding of potential health risks from drug families that target the serotonin pathway in human patients. (...)

Clinical
Jean M. Lauder, Ph.D., Professor of Cell and Developmental Biology at the University of North Carolina School of Medicine at Chapel Hill said: " Dr. Levin's team presents exciting new evidence that serotonin, a brain chemical or "neurotransmitter" that is involved in mood disorders and depression and is targeted by antidepressants like Prozac, plays critical roles in early embryonic (prenatal) development of left-right asymmetry of body organs like the heart, gall bladder, and gut.

"This is the first time that a "neurotransmitter" has ever been shown to be a critical patterning signal during development of the vertebrate body plan. This study provides evidence that early embryonic cells have ways of sensing serotonin other than by the synaptic mechanisms that have previously been described in the nervous system.

"Although neurotransmitters like serotonin are known to regulate development of cells and tissues outside the nervous system, no study has ever before shown that they could regulate such things as the shape, laterality, or placement of tissues or organs in the body.

"The possible clinical significance is that serotonergic drugs, if taken by the pregnant woman, might disrupt normal development of the body plan in the fetus. This study also opens up new possibilities for drug discovery to find therapies to prevent malformations caused by errors in these important aspects of prenatal serotonergic signaling." (...)

- Brist på signalsubstans ger plötslig spädbarnsdöd

Brist på signalsubstans ger plötslig spädbarnsdöd
netdoktor.passagen.se 31.10.2006
Teorierna bakom plötslig spädbarnsdöd har varit många, men nu tror forskare att de funnit förklaringen. Genom att undersöka hjärnorna hos 31 barn som avlidit i plötslig spädbarnsdöd kunde man finna att de hade en nedsatt förmåga att ta emot och förmedla signalsubstansen serotonin i det område i hjärnan, förlängda märgen, som reglerar funktioner som andning, hjärtrytm och vakenhet. Teorin är att dessa barn har en medfödd sårbarhet som gör att de är extra känsliga för riskfaktorer så som att sova på mage eller att ha en rökande mamma. (...)

Källa: Göteborgs-Postens nätupplaga. 061031. (...)

- SSRI-utløst ITP (idiopathic thrombocytopenia purpura)

Alternativer til Seroxat?
lommelegen.no 20.8.2000
Jeg er en kvinne på 36. Jeg har brukt Seroxat mot angst i ca.3 år med utmerket effekt. For 3mnd. siden fikk jeg påvist ITP (idiopathic thrombocytopenia purpura), og måtte slutte brått med Seroxat i tilfelle den var årsaken til ITP. Behandles nå med prednison. Jeg har vansker med å klare meg uten seroxat. Kan du anbefale evt. annen anti-depressiva med samme effekt? Er det mulig jeg kan fortsette med Seroxat? (...)

Seroxat er en medisin som tilhører gruppen som kalles selektive serotonin reopptakshemmere. Det finnes flere andre medisiner som virker på samme måten som Seroxat, men som ikke inneholder samme virkestoffet. Du skulle da ha alle muligheter til å få god effekt av en slik medisin. Du kan lese mer om selektive serotonin reopptakshemmere her på Lommelegen.
ITP er riktignok en veldig sjelden bivirkning av Seroxat. Men siden du har fått ITP, er det vel grunn til å være forsiktig med å bruke medisinen igjen. I hvert fall med tanke på at det finnes flere andre medisiner du kan bruke som virker på samme måten.

Jeg synes du skal oppsøke legen din og ta opp problemet.

Vennlig hilsen Farmasøyt Arne Yndestad (...)

(Anm: trombocytopeni; minka mengd blodplater i blodet; årsaker kan vera mange, noen finst under oppslag for purpura; plateunderproduksjon finst ved pancytopeni, auka platedestruksjon ved ITP, LED, etter transfusjonar, pga kjemikaliar, stråling, medikamentbruk m v, trombocytopeni kan elles koma ved konsumpsjonskoagulopati, ved ulike infeksjonar, hemolytisk uremisk syndrom, kreftspreiing, DIC m v, platene kan vera få pga hypersplenisme, TTP eller bloddilusjon; blødingsfare når trombocytt-talet er mindre enn 0,04 × 1012/l; jf oppslag på thrombocytopenia, oppslag på purpura, amegakaryocytisk trombocytopeni, neonatal alloimmun trombocytopeni; stundom brukast uttrykket trombopeni. EN thrombocytopenia. ET [trombocytt + gr penia fattigdom]. Kilde: Norsk medisinsk ordbok.)

(Anm: What Causes Idiopathic Thrombocytopenic Purpura? In idiopathic thrombocytopenic purpura (ITP), the immune system treats a person's own platelets as if they were invaders in the body, attacking and destroying them. The immune system attacks platelets by making proteins called antibodies. The antibodies bind to platelets (attach) and then are removed by the spleen (an organ that is part of the immune system and helps fight infection). US Department of Health and Human Services. nhlbi.nih.gov.)

- Excessive Inflammation During Stressful Situations Experienced By Depressed Patients

Excessive Inflammation During Stressful Situations Experienced By Depressed Patients
medicalnewstoday.com 5.9.2006
Individuals with major depression have an exaggerated inflammatory response to psychological stress compared to those who do not suffer from depression, according to a study by researchers at Emory University School of Medicine. Because an overactive inflammatory response may contribute to a number of medical disorders as well as to depression, the findings suggest that increased inflammatory responses to stress in depressed patients may be a link between depression and other diseases, including heart disease, as well as contributing to depression itself.

Results of the study, led by Andrew Miller, MD, and Christine Heim, PhD, of Emory's Department of Psychiatry and Behavioral Sciences, are published in the Sept. 1 issue of the American Journal of Psychiatry. (...)

(Anm: De sykdommer, som hevdes er registrert hos såkalte alvorlig deprimerte mennesker, kan i virkeligheten skyldes bivirkninger fra de legemidler som denne gruppen pasienter ofte inntar, dvs. antidepressiva, antipsykotika, sovemidler (sovemedisiner) og beroligende midler osv., ikke såkalte lidelser.)

- Lavt serotoninnivå og aterosklerose

APS: Brain May Be Important Factor In Heart Disease
medpagetoday.com 6.3.2006

• Explain to interested patients that this small preliminary study suggests low serotonin activity may influence behaviors such as smoking or physical inactivity that predispose one to atherosclerosis.
• Inform patients who ask that studies have yet to demonstrate that current anti-depressant treatments can reduce risk for atherosclerosis.

Review
DENVER, March 6 - Brains that make less serotonin appear to have thicker arteries, a preclinical sign of cerebrovascular disease, investigators reported here.

Low serotonin levels explain why some people make lifestyle choices that put them at risk for atherosclerosis, such as smoking and physical inactivity, said Matthew F. Muldoon, M.D., M.P.H., of the University of Pittsburgh at the American Psychosomatic Society meeting.

Or, he added, poor lifestyle choices may drive down serotonin levels in the brain, affecting the neurotransmitter's role in modulating blood pressure, metabolism, and appetite.

But either way, this study is the first to show a connection between serotonin and hardening of the arteries, Dr. Muldoon said. (...)

(Anm: atherosclerosis; aterosklerose; åreforkalking med grunnlag i aterom (sjå fatty streaks og aterom) i årehinna; vil etterkvart føra til at årehinna vert ujamn og knudrete, og til hardning av årehinna og åreveggen elles, det kan koma sår i årehinna, ev plakkruptur (s d) som blir sete for trombose/koagulasjon; tilstanden kan i grunnen oppfattast som ein kronisk inflammasjon med årsak i metabolske, fysiske eller miljømessige skadar som hyperkolesterolemi, høgt blodtrykk eller røyking, mykje homocystein i blodet, arvefaktorar m v og viser i åreveggen foci av monocyttar, makrofagar og proliferasjon av glattmuskelceller i tillegg til feittnedslag som fører til endoteldysfunksjon (s d), ein viktig årsak er visstnok oksidasjon av LDL i åreveggen; han er grunnlag for mange degenerative sjukdommar i hjerne, hjarta, lemmer m v. EN atherosclerosis. ET [gr athere velling + skleros hard]. Kilde: Norsk medisinsk ordbok.))

Serotonin og blod

Study Finds Bleeding Problem with Antidepressants
onlinenews.com 23.11.2006
Some patients who are new users of antidepressants such as Paxil and Prozac and other selective serotonin reuptake inhibitors may run a risk of abnormal bleeding, researchers said. (...)

"Antidepressants with a high degree of inhibition of serotonin reuptake were associated with a 2.6-fold increased risk of bleeding events compared with antidepressants with a low degree of serotonin reuptake inhibition," the report said. The serotonin-related drugs work by providing more of that brain chemical, a substance thought to regulate depression and anxiety. The drugs are most often sold as GlaxoSmithKline’s Paxil and Eli Lilly and Co.’s Prozac. (...)

- Antidepressiva ökar blodflödet i hjärnan

Antidepressiva ökar blodflödet i hjärnan
dagensmedicin.se 9.8.2007
Israeliska forskare visar i en ny studie att behandling med antidepressiv medicin kan normalisera blodflödet i hjärnan hos deprimerade patienter. Behandling med elchocker, ECT, hade inte samma effekt. (...)

Forskarna skriver att det behövs fler och större studier med längre uppföljning för att klarlägga vilken roll blodflödet i hjärnan spelar vid depression.

(Anm: 99mTc-HMPAO SPECT Study of Cerebral Perfusion After Treatment with Medication and Electroconvulsive Therapy in Major Depression. The Journal of Nuclear Medicine 2007; 48: 1273–1278. (PubMed)

Regional cerebral blood flow in mood disorders, V.: Effects of antidepressant medication in late-life depression. Am J Geriatr Psychiatry. 2000 Fall;8(4):289-96.)

Study Of Brain Blood Flow May Lead To Improved Depression Treatment
medicalnewstoday.com 12.8.2007
The usefulness of established molecular imaging/nuclear medicine approaches in identifying the 'hows' and 'whys' of brain dysfunction and its potential in providing immediately useful information in treating depression are emphasized in a study in the August Journal of Nuclear Medicine. (...)

(Anm: Serotonin syndrom (SS), kramper, parkinsonisme osv. (forhøyet kroppstemperatur) (mintankesmie.no).)

- Toxicology Findings in Child and Adolescent Suicides in Virginia: 1987–2003

Toxicology Findings in Child and Adolescent Suicides in Virginia: 1987–2003 (pdf)
Prim Care Companion J Clin Psychiatry. 2006; 8(3): 142–146

Objective: In a follow-up report of child and adolescent suicides in Virginia, we describe postmortem toxicology findings in a subset of these youths. (…)

Conclusions: Antidepressants appeared more commonly among youths committing suicide than those dying by accident or homicide. SSRIs did not appear more commonly among youths committing suicide by poisoning than those committing suicide by gun or hanging. Because our data are descriptive, they are subject to over-interpretation. Cause-effect inferences should not be drawn. (…)

SSRIer virker som ecstasy på sex, aggressivitet, kroppstemperatur etc.

Love rats reveal agony of ecstasy (Kjærlige rotter får agoni av ecstasy)
smh.com.au 7.4.2007
(...) Iain McGregor, professor i psykofarmakologi ved University of Sydney, uttalte i går at det lenge har vært kjent at ecstasy øker nivået av serotonin, et hormon involvert i kontroll av appetitt, humør og angst. Men mange andre midler, inklusive Prozac, aktiverer også serotoninnivåer uten at folk ønsker å omfavne hverandre. For å finne mekanismen bak "kjærlighetsmidlet" ga hans team rotter ecstasy. (...) (Iain McGregor, professor of psychopharmacology at the University of Sydney, said yesterday it had long been known that ecstasy boosted serotonin, a hormone involved in controlling appetite, moods and anxiety. But many other drugs, including Prozac, also activated serotonin levels without making people want to hug each other. Seeking the mechanism that makes it the "love drug" his team fed rats ecstasy.)

Imidlertid bemerket hans team, ut fra resultater publisert tidsskriftet journal Neuroscience, at ecstasys "sosiale" effekt på rotter raskt gikk over.
Etter noen få måneder så skiftet rottene fra å være unormalt vennlige til å være mer antisosiale enn de var før de fikk midlet. Og de plagsomme humørsvingningene synes å være "en permanent forandring" (...) (However, his team, whose results have been published in the journal Neuroscience, also noted ecstasy's "sociable" effect on rats wore off quickly. After a few months the rats turned from being unusually friendly to being more anti-social than before they took the drug. And the ugly mood swing seemed to be "a permanent change".)

Decisions best made on a full stomach
news-medical.net 8.6.2008
(...) Serotonin is synthesized from the amino acid tryptophan and plays an important role as a neurotransmitter; it helps control anger, aggression, body temperature, mood, sleep, sexuality, appetite and metabolism.

Serotonin is also found in red meat, dairy products, nuts, seeds, bananas, tuna, shellfish and soy products and is often referred to as the 'happy hormone' because of it's effects on mood.

Too little can lead to depression but too much can produce feelings of euphoria akin to being high on drugs such as ecstasy.

Commonly used antidepressants such as Prozac work by maintaining higher levels of serotonin in the brain.

Dr. Crockett says the study is one of the first to show a causal link between serotonin and impulse control.

Crockett says this is a controversial issue but because serotonin levels were directly manipulated they were able to see the effect on behaviour.

This does to some extent help to explain why some people become combative or aggressive when hungry because the essential amino acid needed for the body to create serotonin is only obtained through diet. (...)

The research is published in the journal Science. (...)

(Anm: Serotonin Modulates Behavioral Reactions to Unfairness. Science 2008;320(5884):1739.)

- Veteraner som tar PTSD-legemidler dør under søvn

Vets taking PTSD drugs die in sleep (Veteraner som tar PTSD-legemidler dør under søvn)
wvgazette.com 25.5.2008
Hurricane man's death the 4th in West Virginia

A Putnam County veteran who was taking medication prescribed for post-traumatic stress disorder died in his sleep earlier this month, in circumstances similar to the deaths of three other area veterans earlier this year.

Derek Johnson, 22, of Hurricane, served in the infantry in the Middle East in 2005, where he was wounded in combat and diagnosed with post-traumatic stress disorder while hospitalized.

Military doctors prescribed Paxil, Klonopin and Seroquel for Johnson, the same combination taken by veterans Andrew White, 23, of Cross Lanes; Eric Layne, 29, of Kanawha City; and Nicholas Endicott of Logan County. All were in apparently good physical health when they died in their sleep.

Johnson was taking Klonopin and Seroquel, as prescribed, at the time of his death, said his grandmother, Georgeann Underwood of Hurricane. Both drugs are frequently used in combination to treat post-traumatic stress disorder. Klonopin causes excessive drowsiness in some patients. (...)

(Anm: paroksetin (paroxetine); markesføres i Norge under handelsnavn som bl.a. Seroxat; Paxil i USA.)

(Anm: Serotonin syndrom (SS), kramper, parkinsonisme osv. (forhøyet kroppstemperatur) (mintankesmie.no).)

Veterans' families question cause of deaths
wvgazette.com 1.3.2009
Post-traumatic stress syndrome treatment cited

CHARLESTON, W.Va. -- Stan and Shirley White's son Andrew, a Marine reservist, died at home 2 1/2 years after he returned from Iraq. Janette Layne lost her husband, Eric, in similar circumstances after his return from Iraq.

More than a year later, they still don't know if the medication their loved ones were taking for post-traumatic stress disorder contributed to their deaths. (...)

The prescriptions were given by doctors at VA facilities in Huntington, Charleston and a residential program in Cincinnati where Layne had just completed an eight-week in-patient treatment. White's doctor instructed him to take as much Paxil and Seroquel as needed, Shirley White said.

"They said he had lethal amounts in his system," she said. "So, no, we don't have answers."

A second look
Stan White hopes to convince policy-makers in Washington to take a second look at pharmaceuticals prescribed to PTSD sufferers.

How safe are the combinations? How carefully should they be dosed? Should people with PTSD, which sometimes includes forgetfulness and memory loss, be given prescriptions that require careful monitoring? (...)

(Anm: Paxil (Seroxat; generisk navn paroxetine; paroksetin i Norge).

- Här får du ett medel och dina personlighetsdrag kommer att förändras

Antidepressants Make Shrimps See the Light (Antidepressiva får reker til å se lyset)
sciencedaily.com 12.7.2010
ScienceDaily (July 12, 2010) — Rising levels of antidepressants in coastal waters could change sea-life behaviour and potentially damage the food-chain, according to a new study. (...)

Research into the behaviour of shrimps exposed to the antidepressant fluoxetine, showed that their behaviour is dramatically affected. The shrimps are five times more likely to swim toward the light instead of away from it -- making them more likely to be eaten by fish or birds, which could have devastating effects on the shrimp population. (...)

Dr Ford's research was motivated by a species of parasite which can alter the behaviour of aquatic creatures through changing serotonin levels within the brains of the organisms. Serotonin is a neuro-hormone found in many animals, including humans, known to control types of behaviour, such as modulating mood and decreasing anxiety.

Drugs to combat depression in humans are often designed to target levels of serotonin which led to the question of whether they could also alter the behaviour of marine organisms.

Dr Ford said: "Effluent is concentrated in river estuaries and coastal areas, which is where shrimps and other marine life live -- this means that the shrimps are taking on the excreted drugs of whole towns." (...)

(Anm: Anti-depressants make amphipods see the light. Aquatic Toxicology 2010 (Jun 4).)

Prozac Pollution Making Shrimp Reckless (Prozac forurensning gjør reker likeglad)
news.nationalgeographic.com 17.6.2010
Antidepressant's key ingredient is flushed into coastal waters, study says.

There's no happy ending for shrimp exposed to the mood-booster Prozac, according to a new study.

Remnants of antidepressant drugs flushed into waterways worldwide are altering shrimp behavior and making them easier prey, experts say.
(See "Cocaine, Spices, Hormones Found in Drinking Water.")

To mimic conditions in the wild, scientists exposed the estuary-dwelling shrimp Echinogammarus marinus to the antidepressant fluoxetine at levels detected in average sewage-treatment waste. Fluoxetine is the key ingredient in the drugs Prozac and Sarafem.

Shrimp normally gravitate toward safe, dark corners. But when exposed to fluoxetine, the animals were five times more likely to swim toward a bright region of water, the team discovered.

"This behavior makes them much more likely to be eaten by a predator, such as a fish or bird," said study co-author Alex Ford, a biologist at U.K.'s University of Portsmouth.

The fluoxetine likely makes shrimp's nerves more sensitive to serotonin, a brain chemical known to alter moods and sleep patterns, according to the study, recently published in the journal Aquatic Toxicology. (...)

Medicin ändrar personligheten
sr.se 8.12.2009
En typ av antidepressiva medel, så kallade SSRI preparat, ger en personlighetsförändring. Det handlar om minskad ängslighet. Det visar en mindre amerikansk studie på totalt 240 personer. (...)

Elias Eriksson som är professor i farmakologi vid i Göteborg. Han menar att problemet är att SSRI preparat först lanserades som antidepressiva läkemedel, även om de inte har störst effekt där. De ska absolut inte ska användas för personer som är ledsna:

– Om man är ledsen av yttre orsaker bör man inte äta sådant här. Det tror jag är ett av de vanligaste felen till överförskrivning, det är att man skriver ut det här till personer som varken har någon depressions sjukdom eller något ångesttillstånd utan som har en nedstämdhet orsakad av yttre omständigheter. Då ska man inte förskriva de här medlen. Däremot vid depression eller ångettillstånd bör de användas.

Men kan du förstå då om det kan låta obehagligt för personer att höra "här får du ett medel och dina personlighetsdrag kommer att förändras"? (...)

(Anm: Personality Change During Depression Treatment. Arch Gen Psychiatry. 2009;66(12):1322-1330 (December).)

(Anm: personlighetsendring; varig endring i en persons måte å tenke, reagere og være på i personlige og sosiale situasjoner (jfr. personlighet). (…)

Årsaker - Personlighetsendring kan være forårsaket av legemlige sykdommer eller skader som rammer hjernen (bl.a. organisk betingede psykiske lidelser som f.eks. demens), skyldes langvarig misbruk av stoff eller andre rusmidler (f.eks. alkohol), eller forekomme som en del av utviklingen av en alvorlig psykisk lidelse som f.eks. schizofreni. Tilstander som kan minne om varig personlighetsendring, finnes også hos psykologisk sett selvusikre, søkende individer som på jakt etter klare verdier og med behov for å tilhøre et fellesskap trekkes inn i enkelte ekstreme religiøse bevegelser. Kilde: Store norske leksikon.)

(Anm: SSRI-utløst aggresjon? (mintankesmie.no).)

Antidepressiva kan endre din personlighet
nrk.no 7.12.2009
Ifølge en studie utført på vegne av det amerikanske helsevesenet kan medisiner med virkestoffet Paroxetine gjøre folk både mindre nevrotiske og mer utadvendte, skriver Reuters.

Paroxetine finnes i blant annet Paroxat, Paroxetin og Seroxat, som selges som reseptbelagte midler i Norge. (...)

- Det er en dramatisk forskjell, sier Tang, og forklarer at man tidligere har trodd at endring i personligheten kom fordi man fikk depresjonen mer under kontroll. (...)

- Bruk av antidepressiva under svangerskapet linket til høyere risiko for autisme

Antidepressant Use During Pregnancy Linked to Higher Risk of Autism (Bruk av antidepressiva under svangerskapet linket til høyere risiko for autisme)
healthland.time.com 5.7.2011 (Time)
Children whose mothers use antidepressants during pregnancy may be more likely to develop autism than kids whose mothers do not, say researchers in California.

In a study involving data on more than 1,800 children — fewer than 300 of whom had an autism spectrum disorder (ASD) — and their mothers, the scientists found that women who were prescribed drugs to treat depression in the year before giving birth were twice as likely to have children with an ASD, compared with women who did not take antidepressants. The risk was even greater for women who were prescribed the drugs in the first trimester: their children were nearly four times more likely to develop autism or a related disorder.

The study focused on one type of antidepressant, selective serotonin reuptake inhibitors (SSRIs), a class of drug that includes fluoxetine (Prozac), paroxetine (Paxil) and sertraline (Zoloft). These antidepressants work by increasing available levels of the neurotransmitter serotonin surrounding nerve cells in the brain, which helps boost mood. (...)

Antidepressant Use During Pregnancy and Childhood Autism Spectrum Disorders (Bruk av antidepressiva under svangerskapet og autisme)
Arch Gen Psychiatry 2011 (Published online July 4)
(...) Results Prenatal exposure to antidepressant medications was reported for 20 case children (6.7%) and 50 control children (3.3%). In adjusted logistic regression models, we found a 2-fold increased risk of ASD associated with treatment with selective serotonin reuptake inhibitors by the mother during the year before delivery (adjusted odds ratio, 2.2 [95% confidence interval, 1.2-4.3]), with the strongest effect associated with treatment during the first trimester (adjusted odds ratio, 3.8 [95% confidence interval, 1.8-7.8]). No increase in risk was found for mothers with a history of mental health treatment in the absence of prenatal exposure to selective serotonin reuptake inhibitors.

Conclusion Although the number of children exposed prenatally to selective serotonin reuptake inhibitors in this population was low, results suggest that exposure, especially during the first trimester, may modestly increase the risk of ASD. The potential risk associated with exposure must be balanced with the risk to the mother or fetus of untreated mental health disorders. Further studies are needed to replicate and extend these findings. (...)

SSRI's And Environment Strong Autism Contributing Factors Over Genes
Editor's Choice
medicalnewstoday.com 5.7.2011
New research this week points to a link between the use of selective serotonin reuptake inhibitors (SSRIs), a type of antidepressant, and the occurrence of autism in unborn kids. Another study found that among twins, the environment plays a bigger role in the development of autism than genetics which is a game changer considering past investigation into autism cause factors.

Over the past 30 years, the number of children with autism has increased from about 4 in 10,000 to about 40 in 10,000.

First off, research led by Kaiser Permanente Northern California reviewed the medical records of more than 1,600 children, 298 of whom had autism spectrum disorders (ASDs). They found that the risk of having a child with autism spectrum disorder was about twice as high among women who took SSRIs in the year before delivery. That risk was even four times higher in women who took SSRIs during their first trimester. SSRIs include such well-known brands as Prozac, Zoloft, Paxil and Celexa. (...)

Data Confirm Trend of Sharp Rise in ASD Cases (Data bekrefter trend med sterk økning av autismetilfeller)
Psychiatr News 2011;46(14):20 (July 15) (American Psychiatric Association)
Among 388,644 children born in one state from 2001 to 2005, more than 3,000 were enrolled in an early-intervention program for autism spectrum disorders by age 3, and in that period, the numbers rose steeply.

In a reflection of national trends, a recent study of children in Massachusetts reports that diagnoses of autism spectrum disorders (ASDs) are increasing, particularly among boys. The study was published online May 16 in Pediatrics. (...)

They discovered that 1 of every 129 children born in Massachusetts in that five-year period was enrolled in an early intervention for an ASD by age 36 months. Early ASD diagnoses increased linearly from 1 in 178 for the 2001 birth cohort to 1 in 108 for the 2005 birth cohort, an increase of 66 percent. (...)

Serotonin and the Autisms (Serotonin og autisme)
Arch Gen Psychiatry 2011 (Published online July 5)
A Red Flag or a Red Herring?

The struggles to provide mechanistic insight regarding the causes of the autisms (autism spectrum disorder [ASD]) continue as the data mount from the newest population-based studies finding that ASD diagnoses affect 1% to 2% of the population.^1-2 Twin and sibling studies support the highly heritable nature of ASD risk, and at-risk younger siblings may have a recurrence risk of 15% to 20%. The newest estimates concur that rare mutations and copy number variants may account for up to 20% of cases.³ What about the other 80%? The genomecentric emphases have resulted in an opacity regarding the idea that through enhanced risk and/or endophenotype modulation, environmental factors are likely to interact with genetic components to participate at some important level in ASD etiology. Yet, the generation of convincing evidence of specific environmental factors remains a struggle, with the few exceptions of medication (eg, valproate sodium) or prenatal infection. Co-occurrence does not impart guilt, so the many candidates identified based on increases of exposures to a variety of agents that parallel an increase in ASD prevalence remain unsubstantiated. The problem is that even benign environmental elements can affect brain development in experimental systems because the building of well-functioning brain architecture is exquisitely sensitive to both genetic and environmental regulation. So, the field is left with basic findings that implicate a variety of genetic and epigenetic factors, together with associated small to modest increases in odds ratios for ASD due to a lengthening list of investigated environmental factors. (...)

Perhaps it is a coincidence that the odds ratio for ASD risk in the study by Croen and colleagues increases when first-trimester exposure to SSRIs is the sole factor. However, it is exactly that time of human brain development during which cortical and subcortical neuronal populations are being produced, migrating to their final destinations and beginning the long process of wiring. While much occurs later, the establishment of a strong foundation developmentally may be an essential component of healthy brain development. Croen and colleagues note more than once in their article that the study should not be taken as carte blanche for withholding SSRI treatment from pregnant mothers who are suffering the stress of depression and related disorders. Altered neurochemistry and stress response systems during pregnancy may affect the fetus as well. New basic neurobiology studies that focus on the importance of 5-HT in brain development and further advances in analyzing prospectively collected clinical data and outcomes will lead to a sound evidence-based approach to the clinical management of individuals who are suffering during a period that should be among the most joyous in their life. (...)

Is Autism, at Least in Part, a Disorder of Fetal Programming?
Arch Gen Psychiatry 2011 (Published online July 5)
The year 1977 marked an important milestone in the history of autism. In this year, the first twin study in autism was published by Folstein and Rutter¹; it demonstrated a striking difference in concordance rates between monozygous (MZ) and dyzgyous (DZ) twins. The studies that followed reported even higher MZ concordance rates, up to 90%, for a broader phenotype resembling what is currently labeled as autism spectrum disorder (ASD)^2-4 and DZ concordance rates at or close to 0%. This resulted in heritability estimates greater than 90%, suggesting that almost all of the variance in phenotypic expression could be attributed to inherited genetic factors.

There was an important need to revisit those early heritability estimates given that there have been significant improvements in the diagnosis of ASD and that the prevalence rates on which the original models were based are now much greater. In addition, the fact that the concordance for DZ twins was so close to 0% has always been a puzzling finding largely ascribed to the imprecision of the estimates. Family studies of nontwin siblings have suggested that the recurrence risk is closer to 5%, or even 10%, once stoppage rules are taken into account.⁵ Even so, based on these twin studies, ASD was often described as the most heritable of psychiatric disorders. It must be admitted, though, that the field has been frustrated by the difficulty in identifying the specific inherited genetic mechanisms for the etiology of ASD. Even the recent genome-wide association studies have not given us any smoking guns, and the top hits have been difficult to replicate. (...)

- Hormonbrist linket til økt selvmordsrisiko

Hormonbrist ökar självmordsrisken
svt.se 18.8.2011
Hormonet oxytocin har en direkt koppling till självmord. Det har forskare i Sverige kommit fram till. Nu hoppas man på nya behandlingar som kan förhindra självmord.
Oxytocin är ett hormon som utsöndras i kroppen när vi till exempel får massage eller när en mamma ammar sitt barn. Man tror att ämnet minskar stresskänslighet och får oss att må bra och fungera socialt.

Nu har forskare vid Karolinska institutet hittat ett tydligt samband mellan nivåerna av oxytocin i ryggmärgsvätska och allvarliga självmordsförsök.

I studien följde forskarna 28 personer som nyligen försökt genomföra ett självmord och jämförde dessa med 19 personer som inte var självmordsbenägna. Sambanden visade sig vara tydliga. (...)

(Anm: Oxytocin; Oksytocin er et velværehormon som produseres i hypothalamus i hjernen, og føres herfra langs nervefibrer til hypofysebaklappen for lagring og frigjøring etter behov. Hormonet utsondres blant annet ved berøring. Både den som berører og blir berørt skiller ut oksytoscin. (no.wikipedia.org).)

Serotonin, pregnancy and increased autism prevalence: is there a link?
Med Hypotheses. 2010 May;74(5):880-3. Epub 2009 Dec 16.
Abstract The prevalence of autism, a neurodevelopmental condition resulting from genetic and environmental causes, has increased dramatically during the last decade. Among the potential environmental factors, hyperserotonemia during pregnancy and its effect on brain development could be playing a role in this prevalence raise. In the rodent model developed by Whitaker-Azmitia and colleagues, hyperserotonemia during fetal development results in a dysfunction of the hypothalamo-pituitary axis, affecting the amygdala as well as pro-social hormone oxytocin regulation. Dysfunction of the amygdala and abnormal oxytocin levels may underlie many clinical features of ASD. Selective serotonin reuptake inhibitors (SSRI) are the most widely used class of antidepressants drugs, and they are not contraindicated during pregnancy. In this paper, we hypothesize that increased serotonemia during pregnancy, including due to SSRI intake, could be one of the causes of the raising prevalence in autism. If our hypothesis is confirmed, it will not only shed light on one of the possible reason for autism prevalence, but also offer new preventive and treatment options. (...)

Antidepressant Use During Pregnancy Linked to Higher Risk of Autism (Bruk av antidepressiva under svangerskapet linket til høyere risiko for autisme)
healthland.time.com 5.7.2011 (Time)
Children whose mothers use antidepressants during pregnancy may be more likely to develop autism than kids whose mothers do not, say researchers in California.

In a study involving data on more than 1,800 children — fewer than 300 of whom had an autism spectrum disorder (ASD) — and their mothers, the scientists found that women who were prescribed drugs to treat depression in the year before giving birth were twice as likely to have children with an ASD, compared with women who did not take antidepressants. The risk was even greater for women who were prescribed the drugs in the first trimester: their children were nearly four times more likely to develop autism or a related disorder.

The study focused on one type of antidepressant, selective serotonin reuptake inhibitors (SSRIs), a class of drug that includes fluoxetine (Prozac), paroxetine (Paxil) and sertraline (Zoloft). These antidepressants work by increasing available levels of the neurotransmitter serotonin surrounding nerve cells in the brain, which helps boost mood. (...)

(Anm: Antidepressant Use During Pregnancy and Childhood Autism Spectrum Disorders (Bruk av antidepressiva under svangerskapet og autisme). Arch Gen Psychiatry 2011 (Published online July 4).)

Can an increased risk of autism be linked to Paxil? (Kan en øket risiko for autisme linkes til Seroxat (paroxetine)?)
central-pennsylvania.injuryboard.com 15.3.2012
Late last year, a study was published in the Archives of General Psychiatry that suggests a possible link between autism spectrum disorders (ASDs) and maternal use of antidepressant medications during pregnancy. The study—although inconclusive as to a causal link between the two—has gotten quite a bit of attention for the advances it makes in furthering our understanding of what causes ASDs.

The study was aimed at determining whether prenatal exposure to antidepressant medications can be associated with an increased risk of ASD. It was a relatively small study, involving only about 300 children with ASD and 1500 randomly selected children without ASD. The authors concluded that the results suggest that exposure to SSRIs—especially during the first trimester—may “modestly increase the risk of ASD.” The researchers also underscored the need for further studies on this issue, particularly given this study’s small size. (...)

Oxytocin involvement in SSRI-induced delayed ejaculation: a review of animal studies.
J Sex Med. 2007 Jan;4(1):14-28.
INTRODUCTION: Selective serotonin reuptake inhibitors (SSRIs) differ in the severity of induced ejaculation delay. Various studies indicate that oxytocin is involved in sexual behavior. (...)

CONCLUSIONS: Preliminary data suggest that the severity of chronic SSRI treatment-induced delayed ejaculation and the differences between the various SSRIs in inducing ejaculation delay is related to gradual desensitization of 5-HT(1A) receptors on oxytocin neurons. (...)

(Anm: Oxytocin; Oksytocin er et velværehormon som produseres i hypothalamus i hjernen, og føres herfra langs nervefibrer til hypofysebaklappen for lagring og frigjøring etter behov. Hormonet utsondres blant annet ved berøring. Både den som berører og blir berørt skiller ut oksytoscin. (no.wikipedia.org).)

- Ny studie på rotter: SSRI-er reduserer serotonin-nivåer markant i hjernen

New Rat Study: SSRIs Markedly Deplete Brain Serotonin (Ny studie på rotter: SSRI-er reduserer serotonin-nivåer markant i hjernen)
psychologytoday.com 1.11.2010
Study helps explain SSRI "discontinuation syndrome"

Dutch investigators will soon publish an article in Neurochemistry International that sheds light on how SSRI antidepressants affect the serotonergic system over the longer term, and why abrupt discontinuation of an SSRI can be so problematic. The study also serves as a reminder of how the public belief that SSRIs “increase” serotonin levels in the brain is belied by science.

In the drug-maintained rats, serotonin content at the end of 17 days was “reduced by 60% on average in nine areas of the brain,” compared to controls. This depletion appears to be part of a compensatory response to the drug. Since an SSRI blocks the normal reuptake of serotonin from the synaptic cleft, the neurotransmitter stays in this extracellular space longer than normal, and in response, the brain’s synthesis of serotonin dramatically decreases. As a result, serotonin levels in brain tissues end up markedly depleted.

At the same time, the withdrawal of citalopram triggered volatile fluctuations in the rats’ serotonergic systems. Brain synthesis of the neurotransmitter rose, slightly beyond normal levels, but with the drug no longer blocking the reuptake of serotonin from the synaptic cleft, “extracellular” levels of serotonin likely dropped during this withdrawal period. There also was a dramatic jump in “serotonin turnover” during withdrawal, which meant that enzymes were rapidly converting serotonin released into the synaptic cleft into a metabolite, which was then carted off as waste. This would have depleted serotonin from the synaptic cleft as well.

During this withdrawal period, when the serotonergic system was undergoing these dramatic fluctuations, the rats exhibited “increased behavioral reactivity” to a startling sound. The researchers noted that when people withdraw from SSRIs, they may experience a “discontinuation syndrome” marked by “aggression, irritability, agitation, anxiety, and low mood.”

While notable, these results are not particularly surprising. The finding that serotonin in the brain becomes markedly depleted in response to “long-term” treatment with an SSRI is consistent with earlier studies. And the problems associated with SSRI-withdrawal are fairly well known. However, this study is yet more evidence that SSRIs do not “normalize” brain chemistry, which explains why they may be so problematic long-term and why, at the same time, withdrawing from them can be so difficult.

“The combination of the marked reduction of serotonin content and limited synthesis may destabilize brain serotonin transmission during long-term SSRI treatment," the investigators concluded. "These combined effects may compromise the efficacy of an SSRI therapy and facilitate behavioral changes” when the drug is abruptly withdrawn. (...)

(Anm: Biochemical and behavioral effects of long-term citalopram administration and discontinuation in rats: Role of serotonin
Neurochemistry International 2010;57(8):948–957 (December).)

Biochemical and behavioral effects of long-term citalopram administration and discontinuation in rats: Role of serotonin
Neurochemistry International 2010;57(8):948–957 (December)
Abstract

We have investigated effects of continuous SSRI administration and abrupt discontinuation on biochemical and behavioral indices of rat brain serotonin function, and attempted to identify underlying mechanisms.

Biochemistry of serotonin was assessed with brain tissue assays and microdialysis; behavior was assessed as the acoustic startle reflex.

Long-term SSRI administration to rats reduced the content of 5-HT and its main metabolite shortly after inhibition of 5-HT synthesis in many brain areas with more than 50%. Turnover was not appreciably decreased, but significantly increased within 48 h of drug discontinuation. The microdialysis experiments indicate that neuronal release of 5-HT depends strongly on new synthesis and emphasize the role of 5-HT1B receptors in the regulation of these processes. Discontinuation of the SSRI rapidly increased behavioral reactivity to the external stimulus. Additional startle experiments suggest that the increased reactivity is more likely related to the reduced extracellular 5-HT levels than to impaired synthesis.

The combination of the marked reduction of serotonin content and limited synthesis may destabilize brain serotonin transmission during long-term SSRI treatment. These combined effects may compromise the efficacy of an SSRI therapy and facilitate behavioral changes following non-compliance. (...)

Diverse artikler

Scientists Identify Brain Circuitry Associated With Addictive, Depressive Behaviors (Forskere identifiserer hjernekrets knyttet til avhengighetsskapende, depressiv atferd)
medicalnewstoday.com 2.5.2012
Scientists at the Gladstone Institutes have determined how specific circuitry in the brain controls not only body movement but also motivation and learning, providing new insight into neurodegenerative disorders such as Parkinson's disease - and psychiatric disorders such as addiction and depression.

Previously, researchers in the laboratory of Gladstone Investigator Anatol Kreitzer, PhD, discovered how an imbalance in the activity of a specific category of brain cells is linked to Parkinson's. Now, in a paper published online in Nature Neuroscience, Dr. Kreitzer and his team used animal models to demonstrate that this imbalance may also contribute to psychiatric disorders. These findings also help explain the wide range of Parkinson's symptoms - and mark an important step in finding new treatments for those who suffer from addiction or depression.

"The physical symptoms that affect people with Parkinson's - including tremors and rigidity of movement - are caused by an imbalance between two types of medium spiny neurons in the brain," said Dr. Kreitzer, whose lab studies how Parkinson's disease affects brain functions. "In this paper we showed that psychiatric disorders - specifically addiction and depression - might be caused by this same neural imbalance."

Normally, two types of medium spiny neurons, or MSNs, coordinate body movements. One type, called direct pathway MSNs (dMSNs), acts like a gas pedal. The other type, known as indirect pathway MSNs (iMSNs), acts as a brake. And while researchers have long known about the link between a chemical in the brain called dopamine and Parkinson's, Gladstone researchers recently clarified that dopamine maintains the balance between these two MSN types.

But abnormal dopamine levels are implicated not only in Parkinson's, but also in addiction and depression. Dr. Kreitzer and his team hypothesized that the same circuitry that controlled movement might also control the process of learning to repeat pleasurable experiences and avoid unpleasant ones - and that an imbalance in this process could lead to addictive or depressive behaviors. (...)

Serotonin-Related Genes Implicated in PTSD
Psychiatric News 2012;47(9):20-32 (May 04)
Thanks to a major earthquake a quarter-century ago, researchers take another small step toward pinpointing a biomarker for posttraumatic stress disorder.

An innovative study of 200 adults who survived an earthquake in Armenia found a significant association between two genes and the risk for posttraumatic stress disorder (PTSD).

Two variations of tryptophan hydroxylase genes, called TPH1 and TPH2, which control the production of serotonin, were associated with PTSD symptoms, said lead author Armen Goenjian, M.D., online April 5 in the Journal of Affective Disorders. Goenjian is a research professor of psychiatry at the David Geffen School of Medicine at the University of California, Los Angeles.

“To our knowledge, this is the first report that has shown the association of TPH genes with PTSD symptoms,” Goenjian told Psychiatric News. (...)

Depression Linked to Higher Odds for Poor Leg Circulation
health.usnews.com 20.4.2012
In study, depressed patients were more apt to develop peripheral artery disease

FRIDAY, April 20 (HealthDay News) -- Depressed people may be at higher risk for the debilitating circulatory condition known as peripheral artery disease (PAD), a new study suggests.

PAD is due to a narrowing of the arteries in the legs and pelvis. It was known that depression is a risk factor for the constriction of heart arteries, but its link with PAD specifically was unclear.

In this study, researchers led by Marlene Grenon of the University of California, San Francisco, Medical Center examined data on more than a thousand men and women who were followed for about seven years.

At the start of the study, PAD was present in 12 percent of the participants with depression and in 7 percent of those without depression. During the seven-year follow-up, PAD-related events occurred in 9 percent of participants with depression and in 6 percent of those without depression, the researchers said.

One expert wasn't surprised by the findings.

"The study reminds us of the importance of screening all patients for signs and symptoms of depression," said Dr. Lawrence Phillips, an assistant professor in the department of medicine at NYU Langone Medical Center in New York City. "Aggressive treatment of depression can improve modifiable risk factors and decrease the development of both coronary artery disease and peripheral artery disease," he added.

Still, Phillips said more study may be needed to clarify the relationship between depression and PAD. (...)

(Anm: - Brukere av antidepressiva har mer åreforkalkning og dermed økt risiko for hjertesykdom og hjerneslag sammenlignet med ikke-brukere (mintankesmie.no).)

Accumulation of an Antidepressant in Vesiculogenic Membranes of Yeast Cells Triggers Autophagy
PLoS ONE 7(4): e34024 (April 18)
Abstract Many antidepressants are cationic amphipaths, which spontaneously accumulate in natural or reconstituted membranes in the absence of their specific protein targets. However, the clinical relevance of cellular membrane accumulation by antidepressants in the human brain is unknown and hotly debated. Here we take a novel, evolutionarily informed approach to studying the effects of the selective-serotonin reuptake inhibitor sertraline/Zoloft® on cell physiology in the model eukaryote Saccharomyces cerevisiae (budding yeast), which lacks a serotonin transporter entirely. We biochemically and pharmacologically characterized cellular uptake and subcellular distribution of radiolabeled sertraline, and in parallel performed a quantitative ultrastructural analysis of organellar membrane homeostasis in untreated vs. sertraline-treated cells. These experiments have revealed that sertraline enters yeast cells and then reshapes vesiculogenic membranes by a complex process. Internalization of the neutral species proceeds by simple diffusion, is accelerated by proton motive forces generated by the vacuolar H+-ATPase, but is counteracted by energy-dependent xenobiotic efflux pumps. At equilibrium, a small fraction (10–15%) of reprotonated sertraline is soluble while the bulk (90–85%) partitions into organellar membranes by adsorption to interfacial anionic sites or by intercalation into the hydrophobic phase of the bilayer. Asymmetric accumulation of sertraline in vesiculogenic membranes leads to local membrane curvature stresses that trigger an adaptive autophagic response. In mutants with altered clathrin function, this adaptive response is associated with increased lipid droplet formation. Our data not only support the notion of a serotonin transporter-independent component of antidepressant function, but also enable a conceptual framework for characterizing the physiological states associated with chronic but not acute antidepressant administration in a model eukaryote. (…)

New Insight On How Antidepressants Work
psychcentral.com 19.4.2012
Although the antidepressant medications known as selective serotonin reuptake inhibitors (SSRIs) have been on the market for nearly 40 years, no one knows for sure exactly how they work.

A new Princeton study on the action of Zoloft on yeast cells provides tantalizing evidence that depression is not solely linked to the neurotransmitter serotonin.
The findings, published in PLoS ONE, document how sertraline (known by the brand name, Zoloft) accumulated in the membranes of yeast cells. This accumulation occurred between the two lipid layers that make up the cellular membrane, causing a swelling and sharp curvature of the internal membrane. The finding is meaningful because yeast cells lack serotonin.

Although SSRIs are known to regulate serotonin, it is not completely understood how antidepressants interact with the body’s brain cells and what effect, if any, this activity has on treating depression. Antidepressant accumulation has been observed in the membranes of human cells, the researchers report, but is considered benign.

By observing this reaction to sertraline in an organism that does not contain the drug’s conventional target, Ethan Perlstein, Ph.D., and his co-authors have found significant evidence suggesting that antidepressants may have an active effect beyond regulating serotonin.

If the effects of the medication come from the membrane curvature, then the cell membrane could present an additional target for next-generation antidepressants.
“The serotonin transporter is one site where these drugs interact, but we show that’s not all they do,” Perlstein said. “These drugs have multiple effects on various targets in the cell — and one of the targets might be specific membranes themselves.”

More immediately, Perlstein said, the activity of the drug in a serotonin-free organism supports existing research suggesting that depression might also be linked to diminished secretions of brain-derived neurotrophic factor (BDNF), a protein found in the brain. (...)

Although the mitochondrial marker porin is also present in fractions 6–7, we showed above that disrupting proton motive forces with oligomycin actually increased [3H]sertraline accumulation (Fig. 1B), so while association with mitochondrial cannot be ruled out it appears coincidental. (...)

(Anm: Mitochondria (mitokondrie). (mintankesmie.no).)

(Anm: Accumulation of an Antidepressant in Vesiculogenic Membranes of Yeast Cells Triggers Autophagy. PLoS ONE 2012;7(4): e34024 (April 18).)

Psychiatric Medication For Children? Important New Book Gives Pause
boston.com 14.4.2012
Two things most stood out for me in Kaitlin Bell Barnett's new book Dosed: The Medication Generation Grows Up. The first is the stories of women struggling to get off of SSRI's, started in early adolescence, when they decide to get pregnant. The second is Bell Barnett's review of the literature regarding sexual dysfunction as a side effect of SSRIs in adolescence.

The book as a whole has much to say that is very important. As I write in my blurb for the cover:

Dosed is a fascinating, well-researched, and very important book. After reading it, I hope that no parent, pediatrician or psychiatrist will give psychiatric medication to a child or adolescent without very careful consideration of the potential long-term consequences. Bell Barnett shows that these medications are often not a ‘quick fix,’ but rather have deep, lasting impact, not only on physical and emotional health, but also on a person’s core sense of self.

Bell Barnett is a journalist who was herself started on SSRIs as a teenager. Her book intertwines in depth interviews with people who were started on psychiatric medication in childhood and are now young adults, with a journalistic study of the history of psychiatric medication use in children. I could probably write several posts covering all the important issues she addresses, but have chosen to focus on these two.

I first learned of the emerging evidence that SSRIs may cause long term sexual dysfunction last fall when I attended a talk by Robert Whitaker, author of the controversial book about psychiatric illness and medication Anatomy of an Epidemic. I was so alarmed about this data that I wanted to immediately write a blog post about it. But shortly after that talk I received the galleys of Bell Barnett's book. I discovered that she has a through review of the rather scant literature on the subject along with some very poignant stories, so I decided to wait until her book came out. I recommend that anyone who is concerned about this issue (as anyone who takes or prescribes these drugs should be) read her book. The subject is covered in the chapter entitled "Side Effects." Here are a few sample quotes.

A comprehensive review of the literature conducted in 2004 found just one clinical trial that reported erectile dysfunction in a teenager; most clinical guidelines and reviews of SSRIs didn't mention sexual side effects at all.

This is pretty shocking since, as the authors of the study cited above noted, anywhere from 30-40 percent of adults experience some kind of SSRI induced problems with libido, arousal, or orgasm. (...)

Can an increased risk of autism be linked to Paxil? (Kan en øket risiko for autisme linkes til Seroxat (paroxetine)?)
central-pennsylvania.injuryboard.com 15.3.2012
Late last year, a study was published in the Archives of General Psychiatry that suggests a possible link between autism spectrum disorders (ASDs) and maternal use of antidepressant medications during pregnancy. The study—although inconclusive as to a causal link between the two—has gotten quite a bit of attention for the advances it makes in furthering our understanding of what causes ASDs.

The study was aimed at determining whether prenatal exposure to antidepressant medications can be associated with an increased risk of ASD. It was a relatively small study, involving only about 300 children with ASD and 1500 randomly selected children without ASD. The authors concluded that the results suggest that exposure to SSRIs—especially during the first trimester—may “modestly increase the risk of ASD.” The researchers also underscored the need for further studies on this issue, particularly given this study’s small size. (...)

Anticholinergic syndrome
scribd.com (8.3.2012) (Council for InternationalOrganizations of Medical Sciences (CIOMS))
REPORTINGADVERSEDRUGREACTIONS - Definitions of Terms and Criteria for their Use (…)

Preamble
The anticholinergic syndrome is a rare complication of treatment with drugs having anticholinergic properties. The typical clinical picture is one of symptoms of a blockade of central and peripheral cholinergic (parasympathetic) neurones. The form that the syndrome takes should correspond with known anticholinergic properties of the drug in question.Other possible causes of anticholinergic syndrome must be considered before it is diagnosed as an adverse drug reaction. For reporting a singlesymptom of anticholinergic nature, a term precisely describing it (e.g., blurred vision, dry mouth) should be used. (…)

Doktorafhandling viser vej mod nye antidepressive lægemidler
dagensmedicin.dk 28.2.2012
NYT OM NAVNE: Læge Gregers Wegener har påvist, at nitrogen oxid i hjernen påvirker det velkendte signalstof serotonin, der spiller en væsentlig rolle ved eksisterende antidepressiv medicin (...)

Serotonergic modulation of receptor occupancy in rats treated with l-DOPA after unilateral 6-OHDA lesioning
J Neurochem. 2012 Mar;120(5):806-17.
ABSTRACT: Recent studies suggest that l-3,4 dihydroxyphenylalanine (l-DOPA)-induced dyskinesia (LID), a severe complication of conventional l-DOPA therapy of Parkinson's disease, may be caused by dopamine (DA) release originating in serotonergic neurons. To evaluate the in vivo effect of a 5-HT(1A) agonist [(±)-8-hydroxy-2-(dipropylamino) tetralin hydrobromide, 8-OHDPAT] on the l-DOPA-induced increase in extracellular DA and decrease in [(11) C]raclopride binding in an animal model of advanced Parkinson's disease and LID, we measured extracellular DA in response to l-DOPA or a combination of l-DOPA and the 5-HT(1A) agonist, 8-OHDPAT, with microdialysis, and determined [(11) C]raclopride binding to DA receptors, with micro-positron emission tomography, as the surrogate marker of DA release. Rats with unilateral 6-hydroxydopamine lesions had micro-positron emission tomography scans with [(11) C]raclopride at baseline and after two pharmacological challenges with l-DOPA + benserazide with or without 8-OHDPAT co-treatment. Identical challenge regimens were used with the subsequent microdialysis concomitant with ratings of LID severity. The baseline increase of [(11) C]raclopride-binding potential (BP(ND) ) in lesioned striatum was eliminated by the l-DOPA challenge, while the concurrent administration of 8-OHDPAT prevented this l-DOPA-induced displacement of [(11) C]raclopride significantly in lesioned ventral striatum and near significantly in the dorsal striatum. With microdialysis, the l-DOPA challenge raised the extracellular DA in parallel with the emergence of strong LID. Co-treatment with 8-OHDPAT significantly attenuated the release of extracellular DA and LID. The 8-OHDPAT co-treatment reversed the l-DOPA-induced decrease of [(11) C]raclopride binding and increase of extracellular DA and reduced the severity of LID. The reversal of the effect of l-DOPA on [(11) C]raclopride binding, extracellular DA and LID by 5-HT agonist administration is consistent with the notion that part of the DA increase associated with LID originates in serotonergic neurons. (...)

A Brain Chemical That May Cause Gambling Addiction, or konkurs (Et hjernekjemikalie som kan forårsake spilleavhengighet, eller bankerott)
medicaldaily.com 21.2.2012
A chemical in the brain associated with regions involved in sensory and reward systems is important in determining how people deal with the pain of financial loss, scientists have revealed in a paper published on Tuesday in the Molecular Psychiatry journal. (...)

The study revealed that norepinephrine or noradrenaline, which works as both a hormone and neurotransmitter, or chemical messenger, is central to an individual’s neurological response to losing money. (...)

Spillegal av medisin: Tapte 2,5 millioner på 16 måneder
vg.no 6.2.2012
(...) Nå viser studier at risikoen for slike bivirkninger er større enn først antatt.

- Jeg var ikke meg selv. Den medisinen roter med hjernen - lystkontroll og impulskontroll.

Rell Rune Loraas (54) er Parkinson-syk, og har spilt bort alt han eier og mer. I en kommunal leilighet i Tønsberg ser han tilbake på en tid da nettgamblingen tok totalt overhånd. Selv ante Loraas ingenting om at det plutselige spillesuget kunne ha noe å gjøre med medisinene han tok. (...)

The Immunostimulating and Antimicrobial Properties of Lithium and Antidepressants
inewp.com 4.2.2012
(...) Selective serotonin reuptake inhibitors (SSRIs)can destroy such fungi in vitro as Candida and Aspergillus species.[84] Sertraline can remit recurrent vulvovaginal candidiasis in vivo.[85] Munoz-Bellido and colleagues have shown that such antidepressants as sertraline, fluoxetine and paroxetine have antimicrobial activity especially against Gram-positive microorganisms. These anti-depressants also show synergistic activity when combined with some antibiotics against several bacteria.[86] In a separate study Munoz-Bellido andcolleagues tested the in vitro activity of various antibiotics and psychotropic drugs against 32 strains of Corynebacterium urealyticum. Sertraline was the most effective psychiatric drug and it enhanced the activity of ciprofloxacin and tetracycline against all strains.[87] (...)

(...) Depression, antidepressants and immunity
The depressive effect of bereavement and other stresses on immune function is well documented.[88] Impaired lymphocyte function, reduced natural killer cell activity, reduced lymphocyte responses to mitogens and decreased natural killer cellpopulations have been demonstrated in depressives.[89,90] Antidepressants augment natural killer cell activity in vivo and in vitro.[91] The MAOI tranylcypromine enhances cell-mediated immunity.[92] (...)

Conclusions
While lithium is effective against some bacteria and viruses evidence for effectiveness against parasites and fungi is lacking. Antidepressants, on the other hand, are effective against various bacteria, viruses, parasites and fungi. As lithium and anti-depressants have immunopotentiating as well as antimicrobial properties they stand to be effective against a gamut of microorganisms. The response of infection to lithium and antidepressants mirrors depression with subjects responding to TCAs, to SSRIs, to MAOIs or to lithium. An infection should not be labeled refractory to antidepressants untilmany, if not all have been tried. Many comparison studies with antidepressants are biased by the generalization that ‘antidepressants’ lack a specific property when the study involved only one. Anti-depressants are highly specific and humans remarkably variable.

Excessive synthesis of PGs depresses brain and immune function. When depressives with an infection respond to lithium or an antidepressant the response is invariably simultaneous, suggesting that the central actions of the drugs are important.

The immunostimulating actions of lithium and anti-depressants are systemic and suggest central orchestration. While antivirals are not necessarily immunostimulants, the actions of lithium and anti-depressants suggest that immunostimulants are antivirals. The SARS epidemic was a clarion call for immunostimulants. The immunostimulating properties of lithium and antidepressants couldtransform the prevention and treatment of many such infections.

Tachyphylaxis may complicate the treatment of depression[99 – 101] and paradoxical reactions induce or intensify symptoms. These phenomena may interfere with the treatment of infection with lithium and antidepressants. Antidepressants are, paradoxically, capable of activating dormant viruses.[102] Remission of depression in subjectstreated for tuberculosis ushered in the pharmaco-logical treatment of depression.

The wheel will turn full circle when lithium and antidepressants areintegrated into the pharmacology and therapeutics of infection. (...)

Antidepressiva medel fick gamla på fall
dagensmedicin.se 23.1.2012
Personer som lider av demens har ökad risk för fallskador om de använder antidepressiva SSRI-preparat. Och risken ökar med dosen, konstaterar nederländska forskare.

Risken ökade ju högre dosen av läkemedlet var. Personer som tog en låg dos, motsvarande en kvarts definierad dygnsdos, hade 31 procents ökad risk. Bland dem som åt motsvarande en definierad dygnsdos var risken trefaldigad. Personer som också fick lugnande medel hade ytterligare ökad risk för fall.

Forskarnas slutsats är att även låga doser SSRI är förenade med en ökad risk för fallskador hos personer med demens och att risken ökar med dosen. De anser att nya behandlingsprotokoll behöver ta med detta i beräkningen. (...)

(Anm: Dose-response relationship between Selective Serotonin Reuptake Inhibitors and Injurious Falls: A study in Nursing Home Residents with Dementia. British Journal of Clinical Pharmacology 2012 (Accepted, unedited articles published online for future issues).)

SSRIs Boost Risk of Falls in Dementia Patients (SSRI-er øker risiko for fall hos demenspasienter)
medscape.com 19.1.2012
January 19, 2012 – Nursing home residents with dementia who use selective serotonin reuptake inhibitors (SSRIs) have an increased risk of having a fall that causes injury compared with those who do not use SSRIs, new research shows.

Further, the risk is dose-dependent, with those using average doses having 3 times the risk compared with nonusers, the authors, led by Carolyn S. Sterke, MSc, from Erasmus University Medical Center, Rotterdam, the Netherlands, report.

"Even at low doses, SSRIs are associated with increased risk of an injurious fall in nursing home residents with dementia," the authors write.

The use of an SSRI with a hypnotic or sedative increases the risk even further, they add.

The study is published online January 18 in the British Journal of Clinical Pharmacology. (...)

The study showed that the risk of a fall resulting in injury increased with age (hazard ratio [HR], 1.05, 95% confidence interval [CI] 1.01 - 1.09), and use of antipsychotics (HR 1.76, 95% CI 1.18 - 2.63).

Increased risk of falls was seen only with the SSRIs, the authors report. Overall, the HR associated with the use of SSRIs was 2.50 (95% CI, 1.50 - 4.19).

(Anm: Dose-response relationship between Selective Serotonin Reuptake Inhibitors and Injurious Falls: A study in Nursing Home Residents with Dementia. British Journal of Clinical Pharmacology 2012 (Accepted, unedited articles published online for future issues).)

Drug-Induced Parkinsonism in the Elderly: Incidence, Management and Prevention
Drugs Aging. 2012 Jan 17. [Epub ahead of print]
Abstract Drug-induced parkinsonism (DIP) has been claimed to be the most prevalent cause of secondary parkinsonism in clinical practice in the Western world. Since the first descriptions in the early 1950s the prevalence of DIP seems to be increasing and approaching that of idiopathic Parkinson's disease (iPD) due to the aging of the population and the rising of polypharmacotherapy. Despite the wide interest this subject has raised in the past, it seems to be frequently overlooked by the medical community. It is particularly burdensome for the elderly and its management includes recognition of symptoms and identification of risk factors and offending agents. Prompt discontinuation of the causative agent leads to a marked improvement, although the condition might persist or remit slowly in up to 10% of the patients. Risk factors for developing DIP include older age; female sex; cognitive impairment; potency, dose and length of treatment; pre-existing extrapyramidal signs; and, very likely, a background of inherited predisposition. The main causative agents are dopamine receptor antagonists but the list of drugs without such a well known and straightforward mechanism of action is large. All antipsychotics, including atypicals (except clozapine) may produce parkinsonism. Although many drugs cause parkinsonism in a dose-related manner, there is an enormous variation in individual susceptibility. The clinical syndrome is less likely to produce tremor than iPD, and is more likely to be symmetrical, but the two syndromes might not be distinguished in any individual patient. Functional neuroimaging tests, which use ligands that bind to the dopamine transporter, are useful for distinguishing iPD from DIP in doubtful cases in patients treated with antipsychotics. The estimated presynaptic dopamine secreting neurons should be diminished in iPD but normal in DIP produced by dopamine receptor blockers, as assessed by molecular imaging techniques evaluating striatal dopamine transporters (DATs). Prompt recognition and discontinuation of the culprit are the keys to the management of DIP. In persistent cases, specific therapies including anticholinergics and amantadine may provide symptomatic relief. Levodopa and dopamine receptor agonists might be an option in selected cases in which dopamine nerve terminal defects are present. The weight and scope of DIP varies with the age and underlying health of the patient, imposing a significant burden on the elderly who, in many cases, experience significant functional deterioration that leads to hospitalization and has vast economic consequences. This article reviews the epidemiology, pathogenic mechanisms, implicated drugs, clinical features and management of DIP and highlights the need for increased awareness of this iatrogenic condition. (...)

Drug Monitoring
Investigating beneficial drug reactions
BMJ 2012;344 (4 January)
(...) All clinicians are familiar with drugs that have multiple uses. Codeine, for example, may be given to reduce cough (when it may have the adverse effect of constipation) or to treat diarrhoea (when suppressing the cough reflex becomes the unintended adverse effect). (...)

Other examples abound, in the professional and lay literature, such as recent discussion, including on the BBC, concerning clomipramine’s potential to have a beneficial effect on brain tumours. (...)

In general such potential repurposings have been identified serendipitously by alert doctors who have observed an unexpected beneficial effect that might be due to a prescribed drug, in the same way that they might note possible adverse drug reactions. However, adverse reactions are identified in numerous ways that should also be adopted and modified appropriately for beneficial drug reactions. Of course, as with adverse reactions, such possibilities need careful investigation, again using the validated methods already in place. (...)

Linezolid Toxic With Prozac, Other SSRIs, FDA Warns (Linezolid (Zyvox) giftig med Prozac, og andre SSRI-er, advarer FDA)
medpagetoday.com 21.10.2011
The FDA has issued an updated statement on the potential for serious central nervous system toxicity when patients taking serotonergic psychiatric drugs are treated with the antibacterial agent linezolid (Zyvox).

Cases of serotonin syndrome, which is characterized by mental changes, sweating or shivering, muscle twitching, and coordination problems, have been reported as an adverse interaction with linezolid for drugs of the selective serotonin reuptake inhibitor (SSRI) class as well as for serotonin-norepinephrine reuptake inhibitors (SNRI).

These classes of drugs include paroxetine (Paxil), fluvoxamine (Luvox), fluoxetine (Prozac, Symbyax) sertraline (Zoloft), citalopram (Celexa), escitalopram (Lexapro), vilazodone (Viibryd), venlafaxine (Effexor), desvenlafaxine (Pristiq), and duloxetine (Cymbalta).

While the precise mechanism by which linezolid interacts with these drugs has not been determined, it may result from inhibition of monoamine oxidase A. This enzyme is needed for the metabolism of serotonin in the brain, and its inhibition can lead to toxic buildup of this neurotransmitter.

At least one death has been reported.

"Healthcare professionals and patients may not realize that linezolid has monoamine oxidase inhibitor properties," the FDA stated.

Linezolid is used in the treatment of vancomycin-resistant Enterococcus faecium infections, pneumonia, and skin and soft-tissue infections -- including those caused by methicillin-resistant Staphylococcus aureus.

In an emergency situation when treatment with linezolid may be needed for a patient taking a serotonergic psychiatric drug, alternatives should be considered and the risks and benefits carefully weighed, the agency advised.

If linezolid must be used, the serotonergic drug must be stopped immediately, and the patient must be carefully monitored for two weeks for signs of serotonin syndrome -- except if the drug is fluoxetine, which has a long half-life, necessitating five weeks of monitoring.

If treatment with linezolid is considered in a nonemergency situation, the serotonergic agent should be stopped two weeks (five weeks for fluoxetine) before initiation of the antibacterial agent.

The agency also noted that other psychiatric medications have some serotonergic activity, though less than the SSRIs and SNRIs.

It is not known whether linezolid interacts with these other agents, which include tricyclic antidepressants and monoamine oxidase inhibitors.

The FDA notification also advised clinicians to educate their patients about the signs and symptoms of serotonin syndrome, and to report any such events to the agency's MedWatch program. (...)

(Anm: linezolid (antibiotika; Zyvox i USA); Zyvoxid (in Europe), and Zyvoxam (in Canada and Mexico). Generics are also available in India, such as Linospan (Cipla). (en.wikipedia.org).)

Alkohol skadar kvinnor snabbare
svd.se 9.11.2011
Kvinnor drabbas av hjärnskador tidigare än män vid hög alkoholkonsumtion. Redan efter fyra års problematiskt drickande hade det så kallade serotoninsystemet försämrats med 50 procent, visar en forskarstudie.

För män dröjde det tolv år, enligt studien vid Göteborgs universitet.

Serotoninfunktionen reglerar bland annat impulskontroll och sinnesstämning.

42 personer med alkoholberoende ingick i den tvärvetenskapliga studien, som genomfördes vid Sahlgrenska akademin och psykologiska institutionen. Resultaten jämfördes med en kontrollgrupp på 28 personer.

Det är känt sedan länge att kvinnor är mer känsliga för alkoholens effekter. Men att även de kemiska ämnena i hjärnan är mer lättpåverkade är nytt, enligt Kristina Berglund, forskargruppens representant vid psykologiska institutionen.

TT: Varför är kvinnor känsligare?

- Alkohol är vattenlösligt. Och eftersom kvinnor består av mer fett blir alkoholen mer koncentrerad i våra kroppar. Dessutom är vi mindre, säger Berglund.

- Kvinnor och män bryter också ner alkohol på olika sätt i kroppen.

Hon poängterar att undersökningen måste följas upp med ytterligare studier för att se om hypotesen håller.

De personer som ingick i studien drack ungefär lika mycket alkohol oavsett kön - cirka tolv flaskor vin i veckan. De fick själva definiera hur länge de haft ett problematiskt drickande.

Resultatet av studien publiceras i tidskriften Alcoholism: Clinical and Experimental Research nästa år. (...)

Effects of lowered serotonin transmission on cocaine-induced striatal dopamine response: PET [11C]raclopride study in humans
Br J Psychiatry. 2011 May 4. [Epub ahead of print]
BACKGROUND: Low serotonin transmission is thought to increase susceptibility to a wide range of substance use disorders and impulsive traits.
AIMS: To investigate the effects of lowered serotonin on cocaine-induced (1.0 mg/kg cocaine, self-administered intranasally) dopamine responses and drug craving.

METHOD: In non-dependent cocaine users, serotonin transmission was reduced using the acute tryptophan depletion method. Striatal dopamine responses were measured using positron emission tomography with [(11)C]raclopride.

RESULTS: Acute tryptophan depletion increased drug craving and striatal dopamine responses to cocaine. These acute tryptophan depletion-induced increases did not occur in the absence of cocaine.

CONCLUSIONS: The results suggest that low serotonin transmission can increase dopaminergic and appetitive responses to cocaine. These findings might identify a mechanism by which individuals with low serotonin are at elevated risk for both substance use disorders and comorbid conditions. (...)

Mild Strokes May Have Hidden Effects (Milde hjerneslag kan ha skjulte effekter)
health.yahoo.com 29.9.2011
MONDAY, Oct. 3 (HealthDay News) -- Even mild strokes can result in serious but unrecognized disabilities, such as depression, vision problems and difficulty thinking, according to a new study.

The findings, released Monday at the Canadian Stroke Congress in Ottawa, suggest new guidelines are needed on the treatment and management of mild strokes, the researchers said.

"There is no such thing as a mild stroke," said study co-author Annie Rochette, of the University of Montreal, in a news release from the Heart and Stroke Foundation of Canada. "These patients face huge challenges in their daily lives."

After interviewing 200 stroke victims within six weeks of having their first stroke, the researchers found a high rate of sleeplessness and depression among the participants. Nearly 25 percent were clinically depressed. The stroke patients also reported a significant drop in their perceived quality of life, the study revealed.

The researchers said treatment for symptoms of depression, such as fatigue, loss of appetite, lack of concentration, disturbed sleep and thoughts of suicide, should be an important part of recovery for mild stroke patients. (...)

Can drugs drill holes in your brain? (Kan legemidler drille hull i hjernen din?)
blogs.scientificamerican.com 29.9.2011
The idea of drugs tunneling their way through the brain, worms to the mind’s apple, is a frequent metaphor I hear. I wrote on the topic for Discovery’s Curiosity and resurfaced it to prepare material for drug education talks with high schoolers. Here’s a simple look back at the common question, which never fails to remind me just how complex, yet undeniably vulnerable, our brains are:

Drugs may not drill holes actual holes through your brain, but they can turn your mental processing powers into Swiss cheese. Here’s how it works: the brain is filled with different kinds of neurotransmitters, or cells that ferry information. They make our nervous system run and function normally. A good example is a neurotransmitter called dopamine, which fills many roles in the brain, including your motivation, cognition and punishment/reward systems.

Neurotransmitters like dopamine shuttle around and bind to specific receptors to communicate messages in the brain. Drugs can wreak havoc on this system in several ways – they may commit the cellular equivalent of a hostage situation and bind to receptors in the place of neurotransmitters. If this happens, neurotransmitters can’t enter or exit their receptors, and parts of your nervous system can’t communicate with your brain. Worse yet, they can thwart the chemical reactions that create neurotransmitters, your electrical messaging, in the first place. They also may overstimulate or block receptors so that neurotransmitters can’t deliver their messages.

If flooded or blocked, your neuron receptors can become desensitized or oversensitized to neurotransmitters like dopamine. This means your brain isn’t recognizing or receiving the information needed to work your crucial parts of your nervous system, like those that control your emotional or motivation structures. Ultimately, you have “holes” in different parts of your mental systems, and which exact parts depend upon the kind of drug you take.

Here’s a video illustrating the concept from BBC’s “How Drugs Work” series, describing cocaine’s influence on the brain’s dopamine. (...)

(Anm: How Does Cocaine Affect The Brain? - How Drugs Work, Cocaine, Preview - BBC Three (youtube 14.1.2011).)

(Anm: How Drugs Work. Series using visual effects and CGI to examine the effects of drugs on the human body, as well as confronting the myths and controversies that surround them. (bbc.co.uk 2011).)

Mild Strokes May Have Hidden Effects (Milde hjerneslag kan ha skjulte effekter)
health.yahoo.com 29.9.2011
MONDAY, Oct. 3 (HealthDay News) -- Even mild strokes can result in serious but unrecognized disabilities, such as depression, vision problems and difficulty thinking, according to a new study.

The findings, released Monday at the Canadian Stroke Congress in Ottawa, suggest new guidelines are needed on the treatment and management of mild strokes, the researchers said.

"There is no such thing as a mild stroke," said study co-author Annie Rochette, of the University of Montreal, in a news release from the Heart and Stroke Foundation of Canada. "These patients face huge challenges in their daily lives."

After interviewing 200 stroke victims within six weeks of having their first stroke, the researchers found a high rate of sleeplessness and depression among the participants. Nearly 25 percent were clinically depressed. The stroke patients also reported a significant drop in their perceived quality of life, the study revealed.

The researchers said treatment for symptoms of depression, such as fatigue, loss of appetite, lack of concentration, disturbed sleep and thoughts of suicide, should be an important part of recovery for mild stroke patients. (...)

Certain Antidepressants With Blood Thinners May Pose Risk for Heart Patients (Enkelte antidepressiva kan sammen med blodtynnende legemidler utgjøre en risiko for hjertepasienter)
health.yahoo.com 26.9.2011
MONDAY, Sept. 26 (HealthDay News) -- Heart attack patients who take both selective serotonin reuptake inhibitor (SSRI) antidepressants and antiplatelet drugs such as aspirin or Plavix have a higher risk for bleeding than those who take anti-clotting drugs only, a new study finds.

Commonly prescribed SSRIs include Zoloft, Prozac, Paxil and Lexapro.

Antiplatelet drugs prevent blood cells from sticking together and forming a blood clot. Heart attack patients are commonly prescribed antiplatelet therapy to reduce their risk of another heart attack. But there's an increased risk of bleeding, which increases even further when certain other drugs are taken at the same time.

It so happens that many heart attack patients have depression symptoms and are prescribed antidepressants, noted the researchers at McGill University in Montreal.
"We're always concerned about how other medicines might interact with the medicines we know are essential to heart health and recovery after heart attack," said Dr. Kirk Garratt, clinical director of interventional cardiovascular research at Lenox Hill Hospital in New York City. "Although SSRIs are used in only a few cardiac patients, learning that SSRIs can increase [the] risk of bleeding complications could have important implications for how we care for patients after stents and other heart procedures."

In the Canadian study, the researchers looked at more than 27,000 heart attack patients, aged 50 and older, and found that patients taking aspirin or Plavix alone had a similar risk of bleeding. But taking an SSRI antidepressant and aspirin increased the risk of bleeding by 42 percent, and taking an SSRI with both aspirin and clopidogrel (dual antiplatelet therapy) increased the risk by 57 percent.

Bleeding included gastrointestinal bleeding, hemorrhagic stroke or other bleeding that required hospitalization or occurred in the hospital during treatment.
The researchers also found that the risk of bleeding was lower in women and in patients who had angioplasty after their heart attack.

The study appears Sept. 26 in the Canadian Medical Association Journal. (...)

(Anm: Risk of bleeding associated with combined use of selective serotonin reuptake inhibitors and antiplatelet therapy following acute myocardial infarction. CMAJ ( September 26).)

Depression Drugs Could Worsen Bleeding After MI (Legemidler mot depresjons kan forverre blødning etter hjerteinfarkt)
medpagetoday.com 26.9.2011
Depression may accompany myocardial infarction (MI) but prescribing selective serotonin reuptake inhibitors (SSRIs), combined with antiplatelet therapy, carries an increased risk of bleeding, researchers found.

Following MI, those taking aspirin with an SSRI had a 42% increased risk of bleeding compared with taking aspirin alone, reported Elham Rahme, PhD, from McGill University in Montreal, and colleagues.

The risk increased to 49% when patients were taking an SSRI with both aspirin and clopidogrel (Plavix) compared with aspirin alone, according to the study published online in CMAJ.

And when patients added an SSRI on top of dual antiplatelet therapy, the risk of bleeding was 57% higher compared with dual antiplatelet therapy alone.

The risk of bleeding with antiplatelet therapy is always a concern, but it may be increased with other medication use, Rahme and colleagues wrote.

They noted that up to 20% of patients with cardiovascular disease suffer from depression and most of them are prescribed SSRIs. (...)

(Anm: Risk of bleeding associated with combined use of selective serotonin reuptake inhibitors and antiplatelet therapy following acute myocardial infarction. CMAJ ( September 26).)

Derfor gjesper du
kk.no 22.9.2011
Det er ikke nødvendigvis fordi du er trøtt. Men du kan regne med det vil skje oftere framover. (...)

En ny studie publisert i tidsskriftet Frontiers in Evolutionary Neuroscience viser nemlig at gjesping også har som oppgave å regulere temperaturen i hjernen.

Les hele studien her! (ekstern lenke)

Gjesper mindre i varmen
Forskerne dokumenterte gjespefrekvensen hos 160 personer gjennom sommer og vinter i den amerikanske staten Arizona.

Det viste seg raskt at folk gjespet langt mer om vinteren, i motsetning til om sommeren, da utendørstemperaturen var lik eller høyere enn kroppstemperaturen.

Konklusjonen til forskerne var at vi lar være å gjespe i høye sommertemperaturer fordi det ikke har noen hensikt.

Den varme lufta bidrar uansett ikke til å kjøle ned hjernen, slik kjøligere luft gjør. (...)

FDA Warns of Heart Risk with Antinausea Drug (FDA advarer om hjerterisiko med kvalmestillende legemiddel)
JAMA 2011 (September 16)
Patients taking ondansetron to manage chemotherapy-induced nausea may be at risk of heart conditions. (Image: Pamela Moore/iStockphoto.com)
A drug used to combat nausea in patients who are undergoing chemotherapy, radiation, or surgery may cause dangerous changes in heart rhythm, according to preliminary findings from an ongoing safety review by the US Food and Drug Administration.

Ondansetron may alter the electrical activity of the heart, including prolongation of the QT interval, which may lead to a potentially fatal heart rhythm called torsades de pointes. Patients who already have risk factors for heart rhythm abnormalities, including those with heart disease, those who have low levels of potassium or magnesium in their blood, and those taking other medications that have this adverse effect, are particularly vulnerable. (...)

(Anm: Zofran (ondansetron) (pdr.net).)

(Anm: Zofran (ondansetron) (felleskatalogen.no/pasientutgave).)

(Anm: arytmi; hjertearytmi; Hva er hjertearytmi? Hjerterytmeproblemer, hjertearytmier, opptrer når de elektriske impulsene i hjertet ditt som samordner hjerteslagene dine, ikke fungerer skikkelig og får hjertet ditt til å slå for fort, for langsomt eller uregelmessig. (...) (nhi.no).)

FDA Drug Safety Communication: Abnormal heart rhythms may be associated with use of Zofran (ondansetron)
fda.gov 15.9.2011
(...) The U.S. Food and Drug Administration (FDA) is informing the public of an ongoing safety review of the anti-nausea drug Zofran (ondansetron, ondansetron hydrochloride and their generics). Ondansetron may increase the risk of developing abnormal changes in the electrical activity of the heart, which can result in a potentially fatal abnormal heart rhythm.

Facts about Zofran (ondansetron and ondansetron hydrochloride)

• Used to prevent nausea and vomiting caused by cancer chemotherapy, radiation therapy and surgery.
• Is in a class of medications called 5-HT3 receptor antagonists. Works by blocking the action of serotonin, a natural substance that may cause nausea and vomiting.1
• Available as 4 mg and 8 mg tablets, 4 mg and 8 mg orally disintegrating tablets, and oral solution (4 mg/5 mL). Also available as an injection for intravenous use (2 mg/mL).

Changes in the electrical activity of the heart (prolongation of the QT interval of the electrocardiogram [ECG]) — see Data Summary below — can lead to an abnormal and potentially fatal heart rhythm (including Torsade de Pointes). Patients at particular risk for developing Torsade include those with underlying heart conditions, such as congenital long QT syndrome, those who are predisposed to low levels of potassium and magnesium in the blood, and those taking other medications that lead to QT prolongation. (...)

Anti-Nausea Drug Linked to Arrhythmias (Antikvalme (kvalmestillende)- legemiddel linket til arytmi)
medpagetoday.com 15.9.2011
WASHINGTON -- A drug used to treat nausea and vomiting caused by chemotherapy may trigger dangerous and possibly lethal changes in heart rhythms, the FDA warned Thursday.

The drug, ondansetron (Zofran), may increase the risk of "developing prolongation of the QT interval of the electrocardiogram, which can lead to an abnormal and potentially fatal heart rhythm, including Torsade de Pointes," the FDA said.

In a warning issued to clinicians, the FDA said that patients at greatest risk include those with "underlying heart conditions, such as congenital long QT syndrome, [and] those who are predisposed to low levels of potassium and magnesium in the blood" as well as patients who are taking other medications also associated with QT prolongation.

Ondansetron is a 5-HT3 serotonin receptor antagonist, commonly prescribed to prevent nausea and vomiting caused by cancer chemotherapy, radiation therapy, and surgery.

The FDA said it has ordered GlaxoSmithKline, which markets Zofran, to conduct a thorough QT study to determine the degree to which the drug may cause QT interval prolongation. The agency expects the results next summer. (...)

(Anm: arytmi; hjertearytmi; Hva er hjertearytmi? Hjerterytmeproblemer, hjertearytmier, opptrer når de elektriske impulsene i hjertet ditt som samordner hjerteslagene dine, ikke fungerer skikkelig og får hjertet ditt til å slå for fort, for langsomt eller uregelmessig. (...) (nhi.no).)

Thimerosal in Vaccines May Increase Serotonin Neurons in the Brain
americanchronicle.com 2.7.2011
Embryonic exposure to thimerosal, a vaccine preservative, affects early development, say researchers Ida-Eto and colleagues.

Brain toxicity as a result of organomercury compounds is well known. Thimerosal is an organomercury compound which is still widely used as a pediatric vaccine preservative.

Ida-Eto and colleagues found that when pregnant rats are given thimerosal containing injections, it produces a predictable and dramatic increase in serotonergic neurons.

Too much serotonin is linked to agitation or restlessness, diarrhea, fast heart beat, hallucinations, increased body temperature, dilated pupils, twitching, trembling, loss of coordination, nausea, overactive reflexes, rapid changes in blood pressure, and vomiting. If serotonin increases too much, it can be life threatening.

Serotonin is involved in the regulation of several brain processes such as mood, sleep, appetite, memory, and perception. In fact, many other brain and body functions are affected by serotonin, including the heart, muscles, and endocrine systems.

These effects may or may not be reversible.

People who opt to take a gamble on vaccines may choose a thimerosal free version by request. The thimerosal free versions generally cost a bit more, however the loss of quality of life and financial costs to treat lifelong brain disorders that may result from thimerosal exposure is innumerably greater.

(Anm: Embryonic exposure to thimerosal, an organomercury compound, causes abnormal early development of serotonergic neurons. Neurosci Lett. 2011 Jun 6. [Epub ahead of print].)

Serotonin Series: Do You Have Low Serotonin Levels?
about.com 28.5.2011
The most popular treatments for fibromyalgia and chronic fatigue syndrome include increasing the available levels of serotonin, which is best known as a neurotransmitter but also acts as a hormone. SSRI/SNRI drugs do it, supplements such as SAM-e and 5-HTP do it, and some frequently recommended foods do it.

And yet, serotonin levels (and neurotransmitter levels in general) aren't something doctors test for outside of a research environment. In prescribing these medications -- which are highly likely to cause side effects and can even be deadly -- doctors must rely on symptoms. Many of them don't even do that, but simply make the assumption that our diagnoses automatically equate to low serotonin. (If you read last week's Serotonin Series post, you'll see what that's not always a valid assumption.) (...)

Serotonin & Blood Flow in Fibromyalgia & Chronic Fatigue Syndrome
about.com 21.5.2011
We hear a lot about low serotonin in fibromyalgia (FMS) and chronic fatigue syndrome (ME/CFS), and it's usually in relation to its function as a neurotransmitter (chemical messenger in the brain.) However, serotonin is also busy in the rest of your body as a hormone, and body-wide serotonin dysregulation is believed to contribute to many of our symptoms and comorbid conditions.

The name serotonin is derived from its earliest discovered function, which is to narrow the blood vessels -- sero means serum, which is a component of blood. Blood flow irregularities have been noted in both of these conditions:

In FMS, research shows abnormal blood-flow patterns in the brain, with more than normal in some areas and less than normal in others. We don't know the specific effects of this, but researchers do know that blood flow has a significant impact on brain function.

Also in FMS, some researchers theorize that the horrible burning pains we get are due to ischemia (impaired blood flow), which basically means the area "falls asleep" and then gets those painful pins and needles as the blood, and therefore feeling, returns.

In ME/CFS and to a lesser degree in FMS, some research has shown low blood volume, which results in cells that are starving for oxygen and nutrients. Picture being at a high altitude and struggling to catch your breath after not eating all day. That's what every cell in your body may be going through. (...)

Reduced anxiety-like behavior and central neurochemical change in germ-free mice
Neurogastroenterology & Motility 2011;23:255–e119 (March)
Background There is increasing interest in the gut-brain axis and the role intestinal microbiota may play in communication between these two systems. Acquisition of intestinal microbiota in the immediate postnatal period has a defining impact on the development and function of the gastrointestinal, immune, neuroendocrine and metabolic systems. For example, the presence of gut microbiota regulates the set point for hypothalamic-pituitary-adrenal (HPA) axis activity.

Methods We investigated basal behavior of adult germ-free (GF), Swiss Webster female mice in the elevated plus maze (EPM) and compared this to conventionally reared specific pathogen free (SPF) mice. Additionally, we measured brain mRNA expression of genes implicated in anxiety and stress-reactivity.

Key Results Germ-free mice, compared to SPF mice, exhibited basal behavior in the EPM that can be interpreted as anxiolytic. Altered GF behavior was accompanied by a decrease in the N-methyl-D-aspartate receptor subunit NR2B mRNA expression in the central amygdala, increased brain-derived neurotrophic factor expression and decreased serotonin receptor 1A (5HT1A) expression in the dentate granule layer of the hippocampus.

Conclusions & Inferences We conclude that the presence or absence of conventional intestinal microbiota influences the development of behavior, and is accompanied by neurochemical changes in the brain. (...)

Serotonin sex bomb: How to make a mouse bisexual or just really horny (Serotonerg sexbombe: Hvordan gjøre mus biseksuelle eller bare virkelig kåte)
cbsnews.com 24.3.2011
(CBS) Scientists aren't sure whether they have figured out how to make mice bisexual or just so horny that they will mount whatever happens to saunter in their cage, but a fascinating study out of China sheds new light on the role of serotonin in sexual behavior.

Serotonin is a brain chemical long known to affect sex drive in humans. People who take anti-depressants like Prozac and Zoloft, drugs which increases serotonin in the brain, often have lower libidos.

For mice, the problem is particularly acute - give them too much serotonin and they have trouble gaining erections and ejaculating. But take it away and it's game on.

Researchers at Beijing's National Institute of Biological Sciences did just that. Working with male mice that lack a gene which makes serotonin, they introduced mice of both genders into their cages and sat down to watch the sex show.

Turns out the serotonin-deprived mice were quite the performers, mounting both male and female partners about 80 percent of the time. By comparison, normal male mice got funky with females between 60 and 80 percent of the time and didn't have much taste for their more macho counterparts - mounting them only 20 to 30 percent of the time. (...)

(Anm: Molecular regulation of sexual preference revealed by genetic studies of 5-HT in the brains of male mice. Nature 2011 (Published online 23 March).)

Molecular regulation of sexual preference revealed by genetic studies of 5-HT in the brains of male mice
Nature 2011 (Published online 23 March)
Although the question of to whom a male directs his mating attempts^1,2 is a critical one in social interactions, little is known about the molecular and cellular mechanisms controlling mammalian sexual preference. Here we report that the neurotransmitter 5-hydroxytryptamine (5-HT) is required for male sexual preference. Wild-type male mice preferred females over males, but males lacking central serotonergic neurons lost sexual preference although they were not generally defective in olfaction or in pheromone sensing. A role for 5-HT was demonstrated by the phenotype of mice lacking tryptophan hydroxylase 2 (Tph2), which is required for the first step of 5-HT synthesis in the brain. Thirty-five minutes after the injection of the intermediate 5-hydroxytryptophan (5-HTP), which circumvented Tph2 to restore 5-HT to the wild-type level, adult Tph2 knockout mice also preferred females over males. These results indicate that 5-HT and serotonergic neurons in the adult brain regulate mammalian sexual preference. (...)

Drugs Pose Danger to Our Veterans and Service Members
huffingtonpost.com 21.2.2011
The figures have become familiar: the number of veterans and troops in the wars in Iraq and Afghanistan who suffer from post-traumatic stress disorder are at record levels: 300,000 men and women. What isn't so well known is what most of these people experience when they turn to the military for help. They get prescriptions for serious drugs. Multiple prescriptions.

Prozac, Effexor, Elavil or Trazodone for depression. Paxil for depression, obsessive-compulsive disorder or anxiety. Zoloft for depression, obsessive-compulsive disorder, anxiety. Wellbutrin for depression, anxiety, attention deficit disorder. Celexa for anxiety, panic attacks, ADHD. Valium for anxiety and insomnia. Klonopin, Ativan, or Xanax for anxiety and panic attacks. Topamax for migraines. Percocet, Lyrica, or OxyContin for pain. Adderall or Ritalin for ADD, or ADHD. Haldol, Risperdal or Seroquel for psychosis. Ambien, Lunesta, or Restoril for insomnia.

A group of veterans I had the honor and privilege of meeting with recently shared how this pharmaceutical approach to their physical and emotional pain and inability to sleep -- which I discovered is a universally disabling consequence of combat -- quickly alienates them, producing cynicism towards the VA. "They just push pills," one man told me. "They act as if there's a quick fix: just pop these pills." (...)

Arvelig mangel på serotonin gir økt risiko for AD/HD
Tidsskr Nor Legeforen 2011; 131:325 (18.2.2011)
Barna til kvinner med en genetisk betinget defekt i produksjonen av serotonin har økt risko for AD/HD og andre psykiske lidelser. Det viser en norsk studie.

Serotonin er både et hormon og en nevrotransmitter som medierer ulike fysiologiske funksjoner hos mennesker. Virveldyr har gener for to ulike enzymer som er ansvarlig for serotoninproduksjonen i henholdsvis perifere vev (tryptofanhydroksylase 1, TPH1) og hjernen (tryptofanhydroksylase 2, TPH2). Dyrestudier har vist at maternelt produsert serotonin, dannet ved hjelp av TPH1, også har en effekt på den tidlige embryonale hjerneutviklingen. (...)

Dødsdopet tok sju liv før noen reagerte
dagbladet.no 3.2.2011
Etter sju dødsfall ble dødsdopet PMMA i all hast ført opp på den norske narkotikalisten i høst. I EU har stoffet vært under narkotikalovgivningen siden 2002.

Norsk ungdomskoleelev døde
Også i Norge døde en person av stoffet i 2002. En 15 år gammel ungdomskoleelev fra Rygge døde etter å ha tatt tabletter med Mitsubishi-logo. Han hadde en kroppstemperatur på 42 grader da han ble innlagt.

- Det stemmer at det første PMMA-dødsfallet var for snart ti år siden. En 15-årig gutt fra Rygge døde, sier leder i Norsk Narkotikapolitiforening, Anette Gultvedt til Dagbladet.

Til tross for dødsfallet i Norge, og at andre europeiske land valgte å føre opp stoffet på narkotikalisten, skulle det ta ytterligere ni år, og seks nye dødsfall før Statens legemiddelverk i all hast sørget for å få ført stoffet opp på narkotikalista her i landet i høst.

- Legemiddelverket tok initiativ til å få dette stoffet på narkotikalista i oktober, etter nyhetsoppslagene om at seks personer hadde dødd av stoffet, sier seniorrådgiver i Statens Legemiddelverk Anne Sagabråten til Dagbladet. (...)

(Anm: Serotonin syndrom (SS), kramper, parkinsonisme osv. (forhøyet kroppstemperatur) (mintankesmie.no).)

Ett viktig depresjonsgen
aftenposten.no 21.1.2011
En omfattende studie utført av forskere ved University of Michigan har kommet frem til at vår risiko for å bli rammet av depresjon antagelig avgjøres av ett enkelt gen. Dette genet styrer nivåene av signalstoffet serotonin, og hvilken variant av genet hver enkelt har, ser ut til å påvirke hvor effektivt man henter seg inn etter emosjonelle traumer og sterkt stress. Personer med kortere varianter av dette genet er mer utsatt, konkluderer undersøkelsen, som omfatter mer enn 40 000 mennesker. (...)

Antidepressiva förbättrar prognos efter stroke
lakemedelsvarlden.se 10.1.2011
Patienter som fått måttliga motoriska störningar efter en ischemisk stroke kan vara hjälpta av tidig förskrivning med antidepressiva. Det tyder en fransk studie på.

STROKE I den franska studien jämfördes en grupp patienter som fick tidig behandling med fluoxetin och sjukgymnastik med en grupp som fick placebo och sjukgymnastik. Patienterna som fick läkemedlet hade efter tre månader förbättrat sin motoriska förmåga betydligt jämfört med placebogruppen. Totalt ingick 118 patienter i åldern 18-85 år i studien. Andelen som kunde klara sig själva var 26 procent i gruppen som fått fluoxetin och nio procent i placebogruppen.
Forskarnas slutsats är att det behövs längre och större studier innan behandlingen blir klinisk praxis. (...)

Boehringer Ingelheim withdraws libido drug for women
BMJ 2010; 341:c5701 (12 October)
The German drug company Boehringer Ingelheim announced on 8 October that it is withdrawing from development its drug to increase female sexual desire.

The drug, flibanserin, which reduces serotonin concentrations while raising those of dopamine and noradrenaline (norepinephrine), was originally intended to be an antidepressant.

The company made the announcement after negative reviews by an advisory panel of the US Food and Drug Administration in June (BMJ 2010;341:c3339 doi:10.1136/bmj.c3339) and a letter issued by the agency in August in response to the company’s new drug application. (...)

Gen hos mor øker ADHD-risikoen
dagbladet.no 6.10.2010
Norske forskere har funnet en ny risikofaktor for ADHD: Mutasjoner hos mor som gir lavt nivå av signalstoffet serotonin.

MOR PÅVIRKER: Genmutasjoner som gir lavt serotoninnivå hos mor, gir barnet økt risiko for symptomer som kan knyttes til ADHD og andre psykiatriske lidelser som bipolar lidelse.

(Dagbladet): Det lave nivået av serotonin påvirker barnets utvikling under graviditeten, viser den nye norske studien.

- Disse genetiske variantene hos mor ser ut til å påvirke risikoen for ADHD selv om barnet ikke arver genet. Det kan også bety at påvirkningen tidlig i fosterlivet er mer kritisk enn senere, sier stipendiat Anne Halmøy ved Institutt for biomedisin ved Universitetet i Bergen (UiB).

Studien, som er publisert i oktoberutgaven av tidsskriftet Archives of General Psychiatry, knytter lavt serotoninnivå til flere ulike psykiatriske lidelser. (...)

(Anm: ADHD (oppmerksomhetssvikt-hyperaktivitets-syndromet) (attention-deficit/hyperactivity disorder) (mintankesmie.no).)

Common antidepressants can send our moral compasses spinning
arstechnica.com 27.9.2010
(...) This isn't the authors' first look at the impact of serotonin signaling. Two years ago, they reported that lowering the levels of the neurotransmitter serotonin changed subjects' behavior in the Ultimatum Game, which measures their willingness to punish peers for acting unfairly. With less serotonin around, individuals became more sensitive to offers that they perceived as unfair, and rejected them at elevated rates. (...)

Serotonin selectively influences moral judgment and behavior through effects on harm aversion (Serotonin påvirker moralsk dømmekraft og atferd selektivt gjennom effekter på skadelig aversjon (motvilje))
PNAS (Proceedings of the National Academy of Sciences) 2010 (Published online before print September 27)
Aversive emotional reactions to real or imagined social harms infuse moral judgment and motivate prosocial behavior. Here, we show that the neurotransmitter serotonin directly alters both moral judgment and behavior through increasing subjects’ aversion to personally harming others. We enhanced serotonin in healthy volunteers with citalopram (a selective serotonin reuptake inhibitor) and contrasted its effects with both a pharmacological control treatment and a placebo on tests of moral judgment and behavior. We measured the drugs' effects on moral judgment in a set of moral 'dilemmas' pitting utilitarian outcomes (e.g., saving five lives) against highly aversive harmful actions (e.g., killing an innocent person). Enhancing serotonin made subjects more likely to judge harmful actions as forbidden, but only in cases where harms were emotionally salient. This harm-avoidant bias after citalopram was also evident in behavior during the ultimatum game, in which subjects decide to accept or reject fair or unfair monetary offers from another player. Rejecting unfair offers enforces a fairness norm but also harms the other player financially. Enhancing serotonin made subjects less likely to reject unfair offers. Furthermore, the prosocial effects of citalopram varied as a function of trait empathy. Individuals high in trait empathy showed stronger effects of citalopram on moral judgment and behavior than individuals low in trait empathy. Together, these findings provide unique evidence that serotonin could promote prosocial behavior by enhancing harm aversion, a prosocial sentiment that directly affects both moral judgment and moral behavior. (...)

Chocolate Consumption and Effects on Serotonin Synthesis
Arch Intern Med. 2010;170(17):1608 (September 27)
According to the study by Rose et al,¹ chocolate consumption was associated with higher depression ratings. Whether causality exists between the 2 variables is subject to further research. However, other than what was mentioned in the article by Rose et al, there is a plausible physiological mechanism to explain the relation between chocolate and mood.

The ingestion of carbohydrates stimulates the release of insulin which, along with its anabolic effects, promotes amino acids in the blood to enter muscle cells, except for tryptophan.² This will cause a relative increase of tryptophan over other amino acids, which compete for passing the blood-brain barrier.

As a consequence, more tryptophan enters the brain, and there is an increase in the synthesis of serotonin,³ a neurotransmitter postulated to have a major role in mood disorders and a target of many psychopharmaceuticals.

These effects only occur if the ingested high-carbohydrate food is also low in protein, as demonstrated by a study showing that the ingestion of a mixture of carbohydrates and as low as 6% protein reversed the increase in serotonin synthesis.⁴ This probably occurs because food protein has relatively less tryptophan than other amino acids, neutralizing the effect of relatively high blood tryptophan concentrations induced by insulin secretion.⁵

Chocolate composition is very variable, and this was not ascertained in the study by Rose et al,¹ but it is reasonable to hypothesize that chocolate, many kinds of which are rich in sugars and low in protein, can favor serotonin synthesis and influence mood. (...)

(Anm: Mood food: chocolate and depressive symptoms in a cross-sectional analysis. Arch Intern Med. 2010;170(8):699-703.)

Update in Serotonin and Bone (Oppdatering på serotonin og ben)
The Journal of Clinical Endocrinology & Metabolism 2010;95(9):4124-4132
Context: Serotonin (5-HT) may be an important regulatory agent in bone, and agents that modify 5-HT signaling, such as selective serotonin reuptake inhibitors (SSRIs), are in widespread clinical use. (...)

Conclusions: 5-HT may have regulatory effects on bone. Initial preclinical data suggest that its effects may be deleterious and may be regulated by low-density lipoprotein receptor-related protein 5. These studies need confirmation, as well as elucidation, of the biochemical pathways utilized and the feedback loops involved among bone, gut, and perhaps brain. Paradoxically, targeting of 5-HT synthesis and/or signaling in selective tissues may hold promise as an anabolic intervention for bone. Epidemiological data suggest that clinicians should be vigilant about detection of bone disease in patients who are using SSRIs. (...)

Carcinoid syndrome
BMJ 2010; 341:c3941 (23 August)
Carcinoid syndrome consists of symptoms of facial flushing, diarrhoea, and episodic abdominal pain.¹ It is caused by kinins and serotonin secreted from neuroendocrine tumours that arise from neuroendocrine cells found in almost all organs of the body, most commonly the gastrointestinal tract. Only 30-40% of neuroendocrine tumours cause clinical syndromes; ileal neuroendocrine tumours most commonly cause carcinoid syndrome. Over 95% of patients with carcinoid syndrome have metastatic disease. Hormones secreted by the primary tumour are metabolised by the liver and so do not cause symptoms, but symptoms may develop with liver metastases, as these release hormones that bypass the enterohepatic circulation and enter the systemic circulation. (...)

Flushing is the most common symptom, described in 94% of patients in one study.⁹ It is characteristically a sudden onset of pink to red discoloration involving the face and upper trunk, lasting for 5-10 minutes and occurring intermittently and at any time throughout the day, but especially during times of stress. Patients may not notice episodes of flushing; it is commonly noted by observers such as family members. Triggers that lead to flushing and diarrhoea include stress, foods containing tyramine (chocolate, walnut, banana, pineapple, tomato, plum, aubergine, avocado), and alcohol. Diarrhoea occurs in 78-84% of patients⁹; urgency is often associated with cramping abdominal pain, occurring both day and night (often irritable bowel syndrome settles at night time). The cramping abdominal pain occurs after large meals in 50% of patients.9 Symptoms of obstruction are abdominal distension, visible peristalsis, vomiting, or cessation of bowel motions for 1-2 days. Wheezing occurs in 18% of patients and is more common in patients with bronchial neuroendocrine tumours. Other non-specific features include gradual weight loss (30% of cases) and features of right heart failure (seen in 30-40% of cases at presentation).⁹ (...)

Blame your serotonin levels for being a crybaby (Skyld på dine serotoninnivåer om du er en skrikerunge)
dnaindia.com 16.7.2010
Washington, DC: Always end up crying while watching a movie high on emotional quotient? Well, blame your serotonin levels for it, says a new study.
Frederick van der Veen of the Erasmus Medical Centre and colleagues have found that due to the differences in the neurotransmitter some people are more likely to cry in emotional situations than others.

The researchers gave 25 female volunteers a single dose of either paroxetine - a selective serotonin reuptake inhibitor (SSRI) that briefly increases serotonin levels - or a placebo. (...)

Bit of a crybaby? Blame your serotonin levels (Bitt av en skrikerunge? Skyld på dine serotoninivåer)
newscientist.com 15.7.2010
(...) Although SSRIs are used to treat depression, their mood-boosting effects do not normally show up for around six weeks. The women reported no change in mood in the current study. "We're looking at the direct effect of a single dose of paroxetine," says van der Veen, who adds that the findings might help explain why some people report blunted emotions when taking SSRIs.

"Our understanding of the neurobiology of crying is fairly limited," says Christopher Lowry, a serotonin researcher at the University of Boulder in Colorado. "It makes sense that it is tapping into circuitry involving serotonin."

Van der Veen now wants to find out whether genetic differences in serotonin production affect the tendency to cry. (...)

Those Mysterious Army Deaths: An Update (De mystiske dødsfall i hæren: En oppdatering)
blogs.seattleweekly.com 25.6.2010
A Seattle Weekly cover story last December about the Camp Liberty, Iraq, massacre of U.S. soldiers by John Russell, a deranged Fort Lewis sergeant, also focused on other puzzling non-combat deaths, including soldiers dying in their sleep. Now Georgia author Cilla McCain and San Diego neurologist Fred Baughman, who helped us with the cover story, have probed further into the mysterious body count. In a column today at Huffington Post, McCain reports that "if you conduct an internet search with the phrase 'soldier found dead' the results are staggering. Narrow it down even further by including the phrase 'unexplained' and you will begin to get a glimpse of what some would call an epidemic." (...)

Dr. Baughman, a critic on the use of anti-psychotic drugs, undertook a study of the soldier deaths and determined "sudden cardiac death" to be the cause. As he said in a press release last month, "All were diagnosed with PTSD. All seemed 'normal' when they went to bed. And all were on Seroquel (an antipsychotic) Paxil (an antidepressant) and Klonopin (a benzodiazepine). They were not comatose and unarousable," as in many suicides, he said. "These were sudden cardiac deaths."

The military doesn't necessarily agree, but the Pentagon is failing its mission to properly investigate such deaths and determine the causes, whatever they may be, McCain writes:

Between the VA medical doctors and psychiatrists Andrew was going to for help, none tried to assess the effectiveness of these drugs on his PTSD symptoms. They just kept increasing the dosage as if he were a guinea pig in some twisted lab experiment. Whether sudden cardiac death, polypharmacy, or suicide, a prescription tracking system could be a major step toward preventing tragedy. (...)

(Anm: paroksetin (paroxetine); markesføres i Norge under handelsnavn som bl.a. Seroxat; Paxil i USA.)

Dying In Their Sleep: The Invisible Plague Attacking U.S. Soldiers (Dør under søvn: Den usynlige farsott som angriper amerikanske soldater)
huffingtonpost.com 23.6.2010
While doing research for the book Murder In Baker Company, I came to know many military family members from the support group "Home of the Brave." The group's goal is to help one another gain information and justice in the noncombat related deaths of their loved ones. According to the Department of Defense nearly 1 out of 4 fatalities in the military are noncombat related. (...)

Struggling with PTSD compounded by grief over the death of his brother, Andrew sought help from VA doctors. Their first line of defense was to prescribe him 20 mg. of Paxil, 4 mg of Klonopin and 50 mg of Seroquel. These medications helped at first, but later proved ineffective. Instead of changing the course of treatment, the doctors responded by continually increasing his dosage until the Seroquel alone reached a whopping 1600 mg per day. Within weeks of Andrew's death, three more young West Virginia veterans died while being treated for PTSD with the same drugs, prompting Stan and Shirley White to begin a mission to find out what the deaths have in common. (...)

(Anm: paroksetin (paroxetine); markesføres i Norge under handelsnavn som bl.a. Seroxat; Paxil i USA.)

Exploring the neurochemistry of fairness
arstechnica.com 8.6.2010
For many humans, interactions with their fellows are driven in part by an innate sense of fairness. People often base their own actions on what they perceive as being fair, and will frequently attempt to punish those who violate that sense. The complex behavior associated with the sense of fairness can be studied though a simplified test called the "Ultimatum Game." New results published in Science suggest that behavior in these studies can be easily manipulated by treatments that subtly alter the chemistry of the brain. (...)

This follows results from last year, published in the open access journal PLoS one. In that study, researchers were able to manipulate the generosity of offers by altering levels of the neural hormone oxytocin, which is implicated in forming trusting familial bonds. Those with elevated oxytocin made offers that were 80 percent more generous than the placebo controls.

These studies suggest that a basic aspect of human behavior, one that may be a critical contributor to our ability to function in social contexts, is quite sensitive to basic brain chemistry. At a time when there is a great deal of interest in the use and developments of drugs that manipulate this chemistry, they serve as excellent reminders that these drugs will necessarily have side effects and unintended consequences.

Science, 2008. DOI: 10.1126/science.1155577 (...)

Dangerous Drugs for Combat Soldiers (Farlige legemidler for stridende soldate)
Dr. Phil Leveque - Salem-News.com
salem-news.com 28.3.2010
Zombies on the Attack

Anti-depressant drugs are doubly dangerous. Most of them cause a severe drug hangover which is far worse than alcohol. Their adverse side effects are possibly/probably causing or worsening PTSD.

(MOLALLA, Ore.) - I could NOT believe what I was seeing on ABC TV News March 24, 2010; that the Army Shrinkologists (Psychiatrists) were prescribing zombifying drugs to frontline combat troops.

I was a Combat Infantryman, Battalion Scout, Pointman and Forward Observer in WWII. I am not only lucky but astonished that I lived through it. I can thoroughly empathize with the frontline troops in Iraq et cetera and what they are being prescribed as some of the most dangerous zombifying drugs – the anti-depressants such as Prozac, Zoloft and Paxil. These drugs really scramble the brain and have caused many suicides AND accidental deaths by overdose. These drugs are supposed to be treating these Combat Soldiers for Combat Anxiety and Stress but in many/most cases they could be doing the opposite. (...)

Hjerneskanning kan hjelpe schizofrene
forskning.no 11.3.2010
En ny dansk undersøkelse har lokalisert endringer i hjernen på pasienter med schizofreni. Det gir håp om raskere og mer presis behandling. (...)

Det kan ta lang tid å finne ut om et preparat virker, og etter mange ukers forgjeves behandling må pasienten ofte starte forfra med en ny medisin som kanskje heller ikke virker. (...)

Biologiske endringer
Undersøkelsen er publisert i «Archives of General Psychiatry». Ved hjelp av en rekke hjerneskanninger gir forskerne et innblikk i de biologiske endringene i hjernen hos pasienter som lider av schizofreni.

– Det er nøyaktig det samme som med kreftbehandling, forklarer Thomas Werge, som er forskningssjef ved Sankt Hans Hospital.

– Hvis vi vil behandle sykdommen, må vi vite hvor den sitter, og vi må så tidlig som mulig kunne holde øye med om behandlingen virker. (...)

De har undersøkt en gruppe reseptorer i hjernen (se faktaboks), nærmere bestemt den undergruppen som heter serotonin 2A-reseptorer, som påvirkes av mange antipsykotiske medikamenter.

Serotonin er et signalstoff i hjernen, som populært (men upresist) er blitt døpt «lykkestoff» fordi det har vist seg å spille en rolle ved blant annet depresjon.
Nettopp serotonin 2A-reseptoren har tidligere vært diskutert i forbindelse med schizofreni. (...)

The antidepressants maprotiline and fluoxetine have potent selective antiproliferative effects against Burkitt lymphoma independently of the norepinephrine and serotonin transporters.
Leuk Lymphoma. 2010 Mar;51(3):523-39.
The discovery that some selective serotonin transporter- (SSRI) and norepinephrine transporter- (NSRI) targeting antidepressants have the potential to act as anticancer agents adds greatly to their diverse pharmacological application. We report that the SSRI fluoxetine and the NSRI maprotiline are potent antiproliferative agents against human Burkitt lymphoma (BL), having little effect on normal blood cells. (...)

In this study, we also show evidence to support previous reports that the serotonin transporter (SERT) has no involvement in antidepressant-mediated cell death, as SERT-specific ligands were unable to prevent fluoxetine or maprotiline cell death and not all SERT ligands could induce cell death. Although no target has yet been identified for the action of these compounds, the cell death elicited is potent, selective, and worthy of future investigation. (...)

Firm halts antidepressant research
pharmacyeurope.net 5.2.2010
A major pharmaceutical firm is halting research into antidepressants in a bid to save £500m a year in costs by 2012.

GlaxoSmithKline announced the move as it unveiled an 18% rise in full-year pre-tax profits to £7.9bn. This was an increase of 16% to £28.4bn in the 12 months to December 31.

Antidepressant medicines have represented a major part of the company's sales, with more than £2bn generated from Wellbutrin and Seroxat or Paxil. The last drug was criticised by regulators and drew a series of litigations against the company. (...)

GSK to cut more jobs as it ends research into painkillers
business.timesonline.co.uk 4.2.2010
Hundreds of research and development jobs in the UK will go at GlaxoSmithKline, as Europe’s biggest pharmaceuticals company ends development of new depression and pain medicines. (...)

Typically, six large-scale clinical trials have to be carried out on a new antidepressant because of the difficulty in measuring, clinically, whether they have succeeded.

A degree of controversy has attached itself to Paxil, GSK’s biggest-selling antidepressant, which is also known as Seroxat, after it was linked to an increased risk of suicide in some cases. The company has agreed to pay about $100 million (£63 million) to settle a number of lawsuits relating to the drug. (...)

Antidepressants may delay breast milk production
reuters.com 1.2.2010
NEW YORK (Reuters Health) - Widely used antidepressants known as selective serotonin reuptake inhibitors (SSRIs) may delay a woman's breast milk production soon after giving birth, a new study hints.

In a survey of 431 women who gave birth at one U.S. medical center, researchers found that seven of the eight women on SSRIs did not have their breast milk come in within the typical 72 hours of giving birth. On average, their full breast milk production was delayed by about a day compared with other mothers.

In a separate part of the study, the investigators also found that SSRI medication affected the functioning of human cell samples from the breast tissue lining, and appeared to alter breast milk production in lab mice.

After giving birth, women produce a precursor to breast milk called colostrum until their full breast milk comes in; if that shift does not happen within 72 hours, researchers consider it "delayed secretory activation." (...)

Antidepressants May Complicate Breast-Feeding
businessweek.com 27.1.2010
SSRIs appear to delay lactation in new moms, researchers find (...)

"The breasts are serotonin-regulated glands, meaning the breasts' ability to secrete milk at the right time is closely related to the body's production and regulation of the hormone serotonin," study co-author Nelson Horseman, of the University of Cincinnati, said in a news release from the Endocrine Society.

He said this means that SSRIs may "impact serotonin regulation in the breast, placing new mothers at greater risk of a delay in the establishment of a full milk supply." (...)

(Anm: Serotonin Transport and Metabolism in the Mammary Gland Modulates Secretory Activation and Involution. Journal of Clinical Endocrinology & Metabolism 2009 (December 4).)

Serotonin and Sleep: Molecular, Functional and Clinical Aspects
Edited by J. M. Monti, S. R. Pandi-Perumal, B. L. Jacobs, and D. J. Nutt
621 pp, $219
JAMA. 2009;302(18):2036-2037 (November 11)
(...) The book concludes with 4 chapters on serotonin and its significance for clinical disorders and drug actions. In particular, Buchanon et al and Veasey suggest that serotonin neurons are involved in state-dependent control in respiratory modulation. Abnormalities in these neurons could be implicated in such clinical pathologies as sudden infant death syndrome, panic disorder, and obstructive sleep apnea. Argyropoulos et al consider the alteration of sleep in depression and the affects of antidepressants. Winokur and Kamath discuss schizophrenia, the alteration of sleep architecture, and the action of antipsychotic drugs on sleep, revealing a critical role for 5-HT_2A and dopamine D2 receptors. (...)

Bleak Britain: Anti-depressant prescriptions soar even though illness declines
dailymail.co.uk 24.10.2009
Prescriptions for anti-depressants have soared despite fewer patients being diagnosed with depression, research shows.

It reveals the number of prescriptions issued by GPs for drugs including Prozac and Seroxat has more than doubled over the past 11 years.

And it warns the dramatic rise is largely down to more than two million patients taking antidepressants for years at a time - many of them young women. (...)

Professor Kendrick, who led the study, said: 'We estimate more than two million people are taking antidepressants long-term, in particular women aged between 18 and 30.

'Our previous research found although these drugs are said not to be addictive, many patients found it difficult to come off them, due to withdrawal symptoms including anxiety.

'Many wanted more help from their GP to come off the drugs. We don't know how many really need them and whether long term use is harmful. This has similarities to the situation with Valium in the past.' (...)

Seponering af serotonerg antidepressiv medicin
Ugeskr Laeger 2009, October 19 [Epub ahead of print]
Ophørssymptomer er velbeskrevne for stort set alle større grupper af antidepressiva [1]. Et stort antal symptomer er rapporteret, men disse kan inddeles i overskuelige kategorier, se Tabel 1. (...)

[Serotonin syndrome: report of a fatal case and review of the literature] (Serotonin syndrom: rapport om dødelig tifelle og gjennomgang av litteratur)
Rev Clin Esp. 2002 Apr;202(4):209-11.
We report here the case of a patient with fluoxetine and selegiline induced serotonin syndrome, which presented as encephalopathy, generalized myoclonias, fever, stiffness and sweating, complicated with acute renal failure, rhabdomyolysis and disseminated intravascular coagulation findings. The patient died 6 days after admission. This syndrome is discussed, with an analysis of its causes, pathophysiology and therapy. A special emphasis is placed on the clinical issues and differential diagnosis with the malignant neuroleptic syndrome and other clinical entities with which it could be mistaken. General recommendations are provided to avoid this poorly characterized syndrome that, as in our patient, may have a fatal outcome. (...)

Ny årsag til blodpropper kortlagt
politiken.dk 10.6.2009
Små fedtpartikler i blodet øger faren for blodpropper i hjertet, viser forskning. Opdagelsen kan give bedre behandling.

Mængden af en lille fedtpartikel i blodet ved navn lipoprotein(a) er afgørende for risikoen for at få en blodprop i hjertet.

Det viser et omfattende projekt, som forskere ved Herlev Hospital og Københavns Universitet står bag.

Mængden af proteinet er genetisk betinget, og det viser sig, at hver tredje dansker har så stort indhold af det, at der er stærkt forhøjet risiko for, at det kan udløse blodpropper. (...)

Anklages for Anna Nicoles død
nrk.no 9.6.2009
Howard K. Stern og to leger som skrev ut medikamenter til Anna Nicole Smith må nå møte i retten i en høring i august.

Høringen skal avgjøre om det blir rettssak mot de tre. Stern var både Anna Nicole Smiths advokat og kjæreste, mens de to legene var hennes psykiater og allmennlege, melder Reuters. (...)

Case Report
Citalopram-Induced Bleeding Due to Severe Thrombocytopenia
Psychosomatics 50:297-298, May-June
BACKGROUND: In case reports and observational studies, serotonin reuptake-inhibitors (SSRIs) have been linked to an increased risk of bleeding, possibly due to platelet dysfunction as a consequence of serotonin-uptake blockade into platelets. OBJECTIVE: The authors propose that bleeding as a result of SSRI use may also be caused by other mechanisms. (...)

CONCLUSION: As this case report shows, drug-induced immune thrombocytopenia may present another possible mechanism for bleeding in SSRI-treated patients. (...)

Serotonin Rising
Correction to Rosen, N Engl J Med 360(10):957-959 March 5, 2009.
N Engl J Med 2009; 360:2580-2582 (June 11)
To the Editor: Rosen's Perspective article (March 5 issue)¹ highlights recent findings that gut-derived serotonin inhibits bone formation by stimulating serotonin receptors on the preosteoblast.² A critical question is whether serotonin is delivered to bone in some blood element or as free plasma serotonin. The serum serotonin measurements used by Yadav and colleagues² reflect an undefined proportion of the platelet pool and say nothing about the minuscule and often mismeasured free plasma concentrations.³

If the platelet is the delivery vehicle, it is paradoxical that increased platelet serotonin levels in Lrp5-knockout animals and patients with osteoporosis pseudoglioma lead to bone loss,² whereas treatment with selective serotonin-reuptake inhibitors (SSRIs), which lowers platelet serotonin levels by 80 to 95%, also reduces bone mass.⁴ The apparent requirement for maternally derived serotonin in mammalian embryogenesis⁵ poses a similar puzzle: How can gestational SSRI treatment markedly reduce maternal platelet serotonin levels without disrupting embryonic development? Perhaps local tissue uptake and release are crucial in regulating exposures. Finally, given the apparent inhibitory role of serotonin (however delivered) in bone formation,¹,² it is puzzling that the carcinoid syndrome has not been commonly associated with osteoporosis. (...)

Depression may indicate early Parkinson's disease
reuters.com 3.6.2009
NEW YORK (Reuters Health) - Results of a new study provide more evidence that depressive symptoms are an early feature of Parkinson's disease, preceding the characteristic movement problems seen Parkinson's such as tremor and rigid muscles.

In the study, researchers found that starting antidepressant therapy was associated with a twofold increased risk of developing Parkinson's disease in the next 2 years. (...)

Effect of a single dose of citalopram on amygdala response to emotional faces
The British Journal of Psychiatry (2009) 194: 535-540.
(...) Results
Volunteers treated with citalopram displayed a significantly reduced amygdala response to fearful facial expressions compared with placebo.

Conclusions
Such an immediate effect of an SSRI on amygdala responses to threat supports the idea that antidepressants have an earlier onset of therapeutically relevant effects than conventionally thought. (...)

Forelskelse = forhekselse
Du BLIR gal av forelskelse
vg.no 3.5.2009
(...) Ifølge psykiatriprofessor Donatella Marazziti er forelskelse rett og slett en tvangstanke. Hun er leder for psykofarmakologisk laboratorium ved Universitetet i Pisa og har forsket på forelskede hjerner. (...)

Marazzitis forskning avdekket at det er det samme som skjer i hjernen til pasienter med tvangslidelser som i hodene på personer som er hodestups forelsket: Nivået av signalstoffet serotonin i hjernen synker markant. (...)

- Serotonin virker som en slags bremse, og mindre serotonin betyr mindre selvkontroll. Når folk blir forelsket, blir man mer impulsiv og man får færre hemninger. Man blir «besatt» av den man er forelsket i, sier Marazziti. (...)

Da hun undersøkte personer med tvangslidelser, fant hun at nivået av signalstoffet serotonin var 40 prosent lavere enn hos friske personer i en kontrollgruppe. (...)

Når man møter personen man er forelsket i, utløses faktisk det samme stoffet i hjernen som hos narkomane når de ruser seg. MR-bilder av en forelsket hjerne viser at ett område er spesielt aktivt.

- Dopamin frisettes i hjernen, og belønningssenteret, nucleus accumbens, aktiveres. De stedene i hjernen som gir den gode følelsen stimuleres, sier førsteamanuensis og hjerneforsker ved NTNU og St.Olavs hospital, Asta Håberg.

Når man er forelsket i en person, blir man avhengig. Delene av hjernen som har med belønning å gjøre aktiveres, slik at man får en følelse av belønning når man er sammen med personen. (...)

Serotonin Rising — The Bone, Brain, Bowel Connection
NEJM 2009;360:957-959 (March 5)
In a recent article, Yadav et al.¹ elucidated the regulation of gut-produced serotonin by low-density lipoprotein receptor–related protein 5 (Lrp5) and the deleterious effect of serotonin on bone mass. This discovery reflects the rapid advances taking place in bone biology and lends support to three newly understood facts about skeletal physiology. (...)

Serotoninergic receptor 1A in the sudden infant death syndrome brainstem medulla and associations with clinical risk factors
Acta Neuropathologica 2009;117(3):257-265 (March)
(...) This study not only provides further evidence of abnormalities within the brainstem serotoninergic system of SIDS infants, but also shows that these changes may be associated with exposure to clinical risk factors. (...)

(Anm: Brainstem Serotonin in Sudden Infant Death Syndrome. JAMA. 2010;303(18):1810 (May 12).)

(Anm: Brainstem Serotonin in Sudden Infant Death Syndrome—Reply. JAMA. 2010;303(18):1810-1811 (May 12).)

Serotonin Boost Turns Locusts Into Social Swarms
npr.org 29.1.2009
After just a few hours of forced crowding, these locusts experienced a steep rise in the brain chemical serotonin, making the formerly solitary insects attracted to other insects. (...)

Elevated levels of serotonin, the same chemical targeted by some anti-depressant medications, appear to have a transformative effect on the insects' social behavior, according to a report published this week in Science. (...)

Breaking into bone biology: serotonin's secrets
Nature Medicine 2009;15, 145-146 (1 February)
Bedside to Bench Selective serotonin reuptake inhibitors (SSRIs) have been the cornerstone of treatment for depression for over a decade. However, two recent studies have shown that patients who are prescribed SSRIs have lower bone mineral density (BMD) than those taking older, tricyclic antidepressants such as amitriptyline. (...)

Prozac may counter parasite mind control
newscientist.com 17.12.2008
Parasites getting you down? Then take Prozac - if you're a fish, that is.

A behaviour-altering parasitic worm has been found to stymie its host's production of serotonin - the same brain chemical that Prozac and other mood-lifting drugs ramp up.

While there are no plans to medicate infected fish in the wild, researchers hope to use psychiatric drugs to figure out how trematode worms alter the behaviour of California killifish, which live in coastal estuaries. (...)

Serotonin in Gut Linked to Bone Formation (Serotonin i tarm linket til bendannelse)
medpagetoday.com 28.11.2008
NEW YORK, Nov. 26 -- That Thanksgiving turkey may be bad for your bones.

That's one of the implications of a study that -- for the first time -- links the gut to bone formation, according to Gerard Karsenty, M.D., Ph.D., of the Columbia University College of Physicians and Surgeons, and colleagues.

The research, conducted mainly in mice, links serotonin produced in the duodenum to the proliferation of osteoblasts, the cells that create new bone, Dr. Karsenty and colleagues reported in the Nov. 26 issue of Cell.

"This is totally new," Dr. Karsenty said. "We had no clue that the gut had control over bone, and in such a powerful manner." (...)

Until these experiments, Dr. Karsenty said, the function of gut-associated serotonin was not known.

"The findings demonstrate without a doubt that serotonin from the gut is acting as a hormone to regulate bone mass," he said. (...)

Prozac Nation No More?
newsweek.com 8.7.2008
In a new book, psychiatrist James Gordon explains why he believes there's a more effective and drug-free way to treat depression and anxiety. (...)

Do we really need Prozac? James Gordon, founder of the Center for Mind-Body Medicine in Washington, D.C., says there's a better way to treat depression—through diet, exercise and meditation. (...)

There are better ways to do that than taking drugs, which have side effects and don't address the underlying message that depression is bringing—that our lives are out of balance and significant change is necessary. Instead they tell us, "You have a biochemical disorder, here's a drug."

But people with depression do have imbalances in levels of neurotransmitters.
Some people do, I wouldn't deny that. What I'm saying is that there are many ways to address those changes that do less harm and may be more productive in the long run because they give people the sense of control that comes from helping themselves. (...)

. A major study that appeared recently in the New England Journal of Medicine, which reviewed both unpublished and published studies submitted to the FDA, found that, when the unpublished trials were included, antidepressants were not nearly as effective as they've been thought to be. A second study that appeared in February in PLoS Medicine, the online journal, reviewed similar data and found that antidepressants were no better than placebos for mild to moderate depression and only slightly more effective for severe depression. (...)

Serotonin Levels Determine Sense of Fairness
forbes.com 4.6.2008
THURSDAY, June 5 (HealthDay News) -- Levels of a brain chemical known as serotonin govern the way people react to unfair offers when they play the game of life, a new study indicates.

Serotonin, which carries messages between neurons, is involved in emotional control. One recent study found that the expression of anger in women was affected by variations in a gene governing the receptors for serotonin in brain cells.

The new study, reported in the June 5 issue of Science, had people play what is called the Ultimate Game, which is being used widely in psychological and neurological studies. The game has one player proposing a way to split a pot of money. If the offer is accepted by the other player, both get paid. If it is refused, neither gets a payment. (...)

Serotonin Modulates Behavioral Reactions to Unfairness
Science 2008;320(5884):1739
Serotonin (5-HT) has long been implicated in social behavior and impulsivity, but the mechanisms through which it modulates self-control remain unclear. We observed the effects of manipulating 5-HT function on behavior in the Ultimatum Game, where players must decide whether to accept or reject fair or unfair monetary offers from another player. Participants with depleted 5-HT levels rejected a greater proportion of unfair, but not fair offers, without showing changes in mood, fairness judgments, basic reward processing, or response inhibition. Our results suggest that 5-HT plays a critical role in regulating emotion during social decision-making. (...)

Weight Gain May Not Be Based Just on What You Eat
forbes.com 4.6.2008
THURSDAY, June 5 (HealthDay News) -- "You are what you eat" is a frustrating truism familiar to the diet-conscious choosing between carrots and carrot cake. But new research suggests that weight control isn't just a matter of what you put in your mouth, but also how the nervous system is genetically predisposed to process fat.

The theory is based on research with worms that suggests that the brain chemical serotonin -- long known for its appetite control properties -- relies on independent but coordinated nerve pathways to drive not only hunger, but also fat metabolism. (...)

Mood hormone may affect fat, U.S. study finds
reuters.com 3.6.2008
(...) The findings, published in the journal Cell Metabolism, could lead to better diet drugs and treatments for diseases like diabetes.

Serotonin may help the body decide whether to burn off excess calories, or store them as fat, Ashrafi said. (...)

Bare det å øke serotonin-nivåer kan ha alvorlige sideeffekter. Diett-legemidlet fenfluramine, som har den effekt at det øker nivåer av serotonin, ble trukket fra markedet i 1997 etter av og til forårsaket dødelige hjerteklaffskader. (...) (Simply raising serotonin levels can have serious side-effects. The diet drug fenfluramine, which has the effect of raising serotonin levels, was pulled off the market in 1997 after it caused sometimes deadly heart valve damage.)

Vets taking PTSD drugs die in sleep (Veteraner som tar PTSD-legemidler dør under søvn)
wvgazette.com 25.5.2008
Hurricane man's death the 4th in West Virginia

A Putnam County veteran who was taking medication prescribed for post-traumatic stress disorder died in his sleep earlier this month, in circumstances similar to the deaths of three other area veterans earlier this year.

Derek Johnson, 22, of Hurricane, served in the infantry in the Middle East in 2005, where he was wounded in combat and diagnosed with post-traumatic stress disorder while hospitalized.

Military doctors prescribed Paxil, Klonopin and Seroquel for Johnson, the same combination taken by veterans Andrew White, 23, of Cross Lanes; Eric Layne, 29, of Kanawha City; and Nicholas Endicott of Logan County. All were in apparently good physical health when they died in their sleep.

Johnson was taking Klonopin and Seroquel, as prescribed, at the time of his death, said his grandmother, Georgeann Underwood of Hurricane. Both drugs are frequently used in combination to treat post-traumatic stress disorder. Klonopin causes excessive drowsiness in some patients. (...)

A Little Help From Serotonin
newsweek.com 22.1.2008
Could A Single Brain Chemical Hold The Key To Happiness, High Social Status And A Nice, Flat Stomach? (...)

Prozac and its mood-altering cousins all work by boosting serotonin's activity in the brain. So do Redux and fenfluramine, the blockbuster diet drugs that were pulled off the market this fall due to safety concerns. Even Imitrex, the hot new migraine treatment, works its magic via serotonin. Somehow serotonin is implicated in just about everything that matters to us--from winning friends and wielding power to managing anxiety and controlling appetites and impulses. So what is serotonin? How does it work? And why is it in such short supply? Those issues are still murky, but science is yielding some clues. (...)

Risk of GI bleeding increased by drug combo
au.health.yahoo.com 29.10.2007
NEW YORK (Reuters Health) - A drug from the class of antidepressants called selective serotonin reuptake inhibitors (SSRIs), such as Prozac, Zoloft or Paxil, added to a nonsteroidal anti-inflammatory drug (NSAID), such as Motrin, Aspirin or Celebrex, can interact to increase the risk of upper gastrointestinal bleeding, according to a report in current issue of Alimentary Pharmacology and Therapeutics.

"Before I did this study, I didn't worry at all when I saw patients who were on combination SSRIs and NSAIDs," Dr. Yoon K. Loke from the University of East Anglia, Norwich, UK told Reuters Health. "Now that I have seen the fairly substantial excess risk (beyond even what I had imagined beforehand), physicians should carefully review the patients' charts -- do they need to be on these drugs (at all), or are there safer alternatives?" (...)

Like virkningsmekanismer ved løping og antidepressiver
Tidsskr Nor Lægeforen 2007; 127: 2571
Bjørneklett A. On antidepressant effects of running and SSRI
Focus on hippocampal and striatal dopamine pathways. Doktoravhandling. Stockholm: Karolinska Institutet, 2007. ISBN 978-91-7357-246-0
Fysisk aktivitet er en virksom behandlingsmetode ved depresjon, og undersøkelser har vist at den er like effektiv som antidepressive medikamenter. (...)

Avhandlingen er et spennende eksempel på hvordan grunnforskning kan bidra til å belyse viktige kliniske problemstillinger. Den finnes i fulltekstversjon på http://diss.kib.ki.se/2007/978-91-7357-246-0/thesis.pdf (...)

Menn blir impulsive mens kvinner blir deprimerte
vg.no 21.9.2007
ENKEL FOREBYGGING: Trening som sykling og svømming mangedobler serotoninproduksjonen. Det kan være med på å redusere risikoen for depresjon.

Årsaken kan være mangel på det samme stoffet. (...)

Kvinner blir deprimerte, triste og forvirrete. Menn blir derimot irriterte og sinte, tyr til flaska og skjeller ut sjefen eller kona. Men selv om symptomene er helt forskjellige, kan forklaringen være den samme, nemlig mangel på signalsubstansen serotonin i hjernen. (...)

Hovedfunnene ble nylig presentert i tidsskriftet Biological Psychiatry. (...)

Bramness mener Walderhaugs forskning er innovativ og viktig.

- Serotoninsystemet er komplekst, og denne doktoravhandlingen kan bidra til at vi forstår mer. Men den fulle rekkevidden av funnene er det vanskelig å si noe om ennå. (...)

Paroxetine and congenital malformations: meta-Analysis and consideration of potential confounding factors
Clin Ther. 2007 May;29(5):918-26
BACKGROUND: Antidepressants have been commonly used by women of childbearing age. Recent studies suggest that paroxetine, a selective serotonin reuptake inhibitor (SSRI), might specifically increase teratogenic risk. (...)

CONCLUSIONS: Based on the results of this metaanalysis, first-trimester exposure to paroxetine appears to be associated with a significant increase in the risk for cardiac malformation. However, a detection bias cannot be ruled out as contributing to the apparent increased detection of cardiovascular malformation of children exposed in utero to paroxetine. A significantly greater number of women were using paroxetine for anxiety or panic when compared with women using other SSRIs. (...)

Antidepressants Aid Hospitalized Heart Patients
javno.com 19.6.2007
People who have hospitalized with a heart attack or severe angina, appear to be less likely to have heart-related events if they take SSRI.

People who have hospitalized with a heart attack or severe angina -- known by the umbrella term "acute coronary syndrome" -- appear to be less likely to have certain heart-related events subsequently if they're taking a type of antidepressant called a selective serotonin reuptake inhibitor or SSRI, researchers report.

Apart from relieving depression, SSRI drugs also stop platelets from clumping together, the authors note in the American Journal of Medicine, and they suspect this characteristic may benefit heart patients. (...)

Eternal sunshine
observer.guardian.co.uk 11.5.2007
It's sold as happiness in a blister pack - a cure-all that has changed the way we think about wellbeing. As Prozac reaches its 20th birthday, Anna Moore presents 20 things you need to know about the most widely used antidepressant in the world (...)

2: Bio-babble has replaced psychobabble
Serotonin was not well known 20 years ago. Now, if you ask the person sitting beside you what it is, he or she may tell you it is linked to happiness, that levels get low in depressed people ... that Prozac tops them up ... so does chocolate ... or aerobics ... maybe yoga ...

Except it isn't strictly true. Or has been repeatedly challenged. And is yet to be proven. According to David Healy, professor of psychiatry at Cardiff University and author of Let Them Eat Prozac, it's pure 'bio-babble' which has replaced the psychobabble of the Sixties and Seventies. Healy spent a decade studying the neurotransmitter serotonin in depressed people and found little evidence to support the theory of 'chemical imbalance'. (...)

Cases of Fen-Phen and SSRI-Related Lung Disorder Rise
By Evelyn Pringle
lawyersandsettlements.com 16.4.2007
Washington, DC: In the fall of 1997, American Home Products Corporation, which became Wyeth in 2002, withdrew the drugs Pondimin (fenfluramine), and Redux (dexfenfluramine), which were prescribed together with phentermine for weight loss, in a combination called "fen-phen," for short.

Fen-phen causes the life-threatening lung disorder known as primary pulmonary hypertension, or PPH. According to the Pulmonary Hypertension Association, PPH is a rare blood vessel disorder of the lung in which the pressure in the pulmonary artery rises above normal levels and can become life threatening.

As the blood is pumped through the arteries in the lungs, it receives oxygen; this oxygenated blood returns to the heart where it is then transported to the rest of the body through the aorta and other arteries. Changes to the pulmonary artery can cause the vessel to tighten, limiting the passage of blood, and increasing the pressure in the artery, according the Lung Disorder web site. (...)

According to the Lung Disorder educational information web site, PPH is difficult to study because it is so rare. Of the estimated 300 cases diagnosed each year in the US, the majority occur in women between the ages of 21 and 40. (...)

SSRIs sold in the US include Prozac, Zoloft, Paxil, Celexa, Lexapro, and the various generic versions of the drugs.

Babies with PPHN, the FDA says, have abnormal blood flow through the heart and lungs, do not get enough oxygen to their bodies and can become very sick and die. (...)

The FDA warning was based on a study in the February 9, 2006, New England Journal of Medicine, led by Dr Christina Chambers, at the University of California in San Diego, which found a 6-fold increased risk of PPH in infants exposed to SSRIs after the 20th week of pregnancy. (...)

Oxytocin involvement in SSRI-induced delayed ejaculation: a review of animal studies.
J Sex Med. 2007 Jan;4(1):14-28.
INTRODUCTION: Selective serotonin reuptake inhibitors (SSRIs) differ in the severity of induced ejaculation delay. Various studies indicate that oxytocin is involved in sexual behavior. (...)

CONCLUSIONS: Preliminary data suggest that the severity of chronic SSRI treatment-induced delayed ejaculation and the differences between the various SSRIs in inducing ejaculation delay is related to gradual desensitization of 5-HT(1A) receptors on oxytocin neurons. (...)

(Anm: Oxytocin; Oksytocin er et velværehormon som produseres i hypothalamus i hjernen, og føres herfra langs nervefibrer til hypofysebaklappen for lagring og frigjøring etter behov. Hormonet utsondres blant annet ved berøring. Både den som berører og blir berørt skiller ut oksytoscin. (no.wikipedia.org).)

- Turte ikke å oppsøke lege
side2.no 13.2.2007
Anna Nicole Smith turte ikke å oppsøke lege fordi hun var redd for medieoppmerksomheten.

Dette forteller Bonnie Stern som er søsteren til Anna Nicole Smiths kjæreste Howard K. Stern. Storesøsteren Bonnie har nylig snakket med broren sin som fortalte henne at Smith hadde 40 i feber dagen hun døde. Ifølge Bonnie hadde ikke Howard vært tilstede da Anna Nicole døde, men han og en sykepleier hadde forsøkt å kjøle henne ned. (...)

Multiple Serotonergic Brainstem Abnormalities in Sudden Infant Death Syndrome
JAMA. 2006;296:2124-2132 (November 1)
Context The serotonergic (5-hydroxytryptamine [5-HT]) neurons in the medulla oblongata project extensively to autonomic and respiratory nuclei in the brainstem and spinal cord and help regulate homeostatic function. Previously, abnormalities in 5-HT receptor binding in the medullae of infants dying from sudden infant death syndrome (SIDS) were identified, suggesting that medullary 5-HT dysfunction may be responsible for a subset of SIDS cases. (...)

Conclusions Medullary 5-HT pathology in SIDS is more extensive than previously delineated, potentially including abnormal 5-HT neuron firing, synthesis, release, and clearance. This study also provides preliminary neurochemical evidence that may help explain the increased vulnerability of boys to SIDS. (...)

Fed mad kan give depression
bt.dk 29.9.2006
Depression kan blive danskernes nye livsstilssygdom. Ny hjerneforskning tyder nemlig på, at åreforkalkninger i hjernen kan føre til depression.

Når danskerne ryger, drikker og spiser fed mad hjemme i hjørnesofaen, sætter de ikke kun kroppens trivsel på spil. Saftige burgere og sprøde pomfritter giver nemlig forkalkede blodårer, og ny hjerneforskning tyder på, at åreforkalkninger i hjernen hos nogle mennesker kan føre til depression.

- Vi tror, at man for eksempel ved at sænke sit kolesteroltal og spise ordentligt kan formindske sin risiko for depressioner, fortæller Rikke Dalby, der er forsker ved Center for Psykiatrisk Grundforskning.

Hun har opdaget, at ændringer i blodkar i visse områder af hjernen giver depression, og de forandrede blodkar kan skyldes forkalkede blodårer. Rikke Dalby understreger, at der også er mange andre årsager til sygdommen, men usund livsstil giver dårligere odds i kampen mod en depression. (...)

Hjerner på utstilling
aftenposten.no 10.3.2006
Over 2800 menneskehjerner er utstilt ved et museum i Lima. (...)

Grise på ecstasy bliver triste
bt.dk 9.3.2006
Små grise har gennem de seneste tre år fået forskellige doser af det forbudte stof ecstasy i et forsøg på at kortlægge, hvordan misbrug af stoffet påvirker mennesker.

Forsøg med ecstasy til grise i Århus kan forklare sammen-hængen mellem misbrug og depression, skriver metroXpress.

Små grise har gennem de seneste tre år fået forskellige doser af det forbudte stof ecstasy i et forsøg på at kortlægge, hvordan misbrug af stoffet påvirker mennesker.

Som led i et videnskabeligt forsøg på PET Center ved Århus Sygehus har grisene fået indsprøjtet ecstasy, hvorefter forskerne har scannet grisene og undersøgt forandringerne i deres hjerner.

- Grisens hjerne minder meget om den menneskelige hjerne. Vi har påvist, at ecstasy frigør et stof i hjernen, der hedder serotonin, og vi ved, at netop det har en klar sammenhæng med depression, siger dyrlæge, ph.d. Aage Kristian Olsen, Århus Sygehus.

- På den baggrund kan vi fastslå, at misbrugere af ecstasy tilsyneladende risikerer at udvikle depression på grund af den langvarige effekt på hjernen, siger han.

Forskerne har desuden set grise miste kontrollen over deres kropstemperatur under påvirkning af ecstasy. Kroppens naturlige termostat går i stykker, og grisenes temperatur stiger dramatisk.

- Det er den samme effekt, man ser hos personer, der mister livet i en rus af ecstasy, siger Aage kristian Olsen. (...)

Behandling av søvnvansker
SLK-publikasjon 2000:08
legemiddelverket.no (SLK-publikasjon 2000:08)
(...) Under REM-søvn er det ikke temperaturregulering. Dette medfører
oppvåkning når omgivelsestemperaturen er for høy eller for lav. (...)