MinTankesmie

- Hvorfor antidepressiva ikke alltid virker

Why Antidepressants Don't Always Work (Hvorfor antidepressiva ikke alltid virker)
depression.about.com 26.10.2009
Ifølge forskere ved Northwestern University har halvparten av de som får antidepressiva ingen nytte av midlene. Forskningen synes å indikere at det kan skyldes at hva vi tror trigger depresjon er fullstendig feil. (...) (According to background information provided in a new paper by Northwestern University researchers, over half of antidepressants fail to provide relief to depression sufferers. Their research seems to indicate it may be because what we believe about what triggers depression is entirely wrong.)

Konsekvensen av disse resultater? Redei og hennes gruppe konkluderte at stress ikke spiller noen rolle i trigging av genetiske endringer knyttet til depresjon; og, dersom stress ikke spiller noen rolle ved depresjon innebærer dette at antidepressiva, som stort sett er testet på dyr ved å stresse dyrene og så observere hvordan antidepressiva modifisere deres atferd, i virkeligheten behandler stress, ikke depresjon. (The implication of these results? Redei and her team concluded that stress does not play a role in triggering the genetic changes associated with depression; and, if stress does not play a role in depression then this means that antidepressants, which are generally tested on animals by stressing the animals and then observing how the antidepressant modifies their behavior, are actually treating stress, not depression.)

Redei sier at legemiddelutviklere har fokusert på effekten (stress) snarere enn årsaken til depresjon. "Det er derfor det tar så lang tid for midlene å virke og hvorfor de ikke er effektive for mange mennesker," forklarte Redei. De behandler faktisk ikke depresjon i det hele tatt. (...) (Redei says that drug developers have been focusing on the effect (stress) rather than the cause of depression. "That's why it takes so long for them to work and why they aren't effective for so many people," explained Redei. They are not actually treating depression at all.)

Northwestern Research Finds Antidepressant Drugs Aim At Wrong Target (Northwestern-forskning viser at antidepressiva bommer på målet)
medicalnewstoday.com 25.10.2009
More than half the people who take antidepressants for depression never get relief.

Why? Because the cause of depression has been oversimplified and drugs designed to treat it aim at the wrong target, according to new research from the Northwestern University Feinberg School of Medicine. The medications are like arrows shot at the outer rings of a bull's eye instead of the center. (...)

Both findings are significant because these beliefs were the basis for developing drugs currently used to treat depression.

Redei, the David Lawrence Stein Professor of Psychiatry at Northwestern's Feinberg School, found powerful molecular evidence that quashes the long-held dogma that stress is generally a major cause of depression. Her new research reveals that there is almost no overlap between stress-related genes and depression-related genes.

"Dette er en stor og statistisk sterk studie," uttalte Redei. "Denne forskningen åpner opp for nye veier for utvikling av antidepressiva som kan være mer effektive. Der har ikke vært et antidepressiva basert på et nytt konsept på 20 år." (...) ("This is a huge study and statistically powerful," Redei said. "This research opens up new routes to develop new antidepressants that may be more effective. There hasn't been an antidepressant based on a novel concept in 20 years.")

Why Antidepressants Don't Work For So Many
northwestern.edu 23.10.2009
CHICAGO --- For more than half the people who take antidepressants, relief from their symptoms never comes.

Why? Because the cause of depression has been oversimplified and drugs designed to treat it aim at the wrong target, according to new research from the Northwestern University Feinberg School of Medicine. The medications are like arrows shot at the outer rings of a bull's eye instead of the center. (...)

Advarsler

January 2009 Safety Labeling Changes (Januar 2009 sikkerhetsendringer pakningsvedlegg (Seroxat (Paxil), Celexa, Cipramil, Zoloft, Cybalta, Efexor, Prozac, Venlafaxine, Pristiq etc.))
fda.gov 6.3.2009
- Summary of safety-related revisions to the BOXED WARNING, CONTRAINDICATIONS, WARNINGS, PRECAUTIONS, and ADVERSE REACTIONS sections of drug Prescribing Information, plus Patient Package Inserts and Medication Guides. (Posted 03/06/2009) (…)

WARNINGS
Serotonin Syndrome or Neuroleptic Malignant Syndrome (NMS)-like Reactions

WARNINGS
The development of a potentially life-threatening serotonin syndrome or Neuroleptic Malignant Syndrome (NMS)-like reactions have been reported with SNRIs and SSRIs alone, including Celexa treatment, but particularly with concomitant use of serotonergic drugs (including triptans) with drugs which impair metabolism of serotonin (including MAOIs), or with antipsychotics or other dopamine antagonists (...)

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

Fosterskader

Use of antidepressants during pregnancy and the risk of spontaneous abortion (Bruk av antidepressiva under svangerskapet og risiko for spontanabort)
CMAJ 2010; 182 (10) (July 13)
(...) Interpretation: The use of antidepressants, especially paroxetine, venlafaxine or the combined use of different classes of antidepressants, during pregnancy was associated with an increased risk of spontaneous abortion. (...)

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

Plaintiffs Hoping for More Paxil Birth Defects Settlements (Saksøker håper på flere flere forlik i saker om fødselsdefekter utløst av Seroxat (Paxil))
lawyersandsettlements.com 5.7.2010
Boston, MA: Although very little information has been released concerning the settlement of Paxil birth defects lawsuits, news reports indicate that approximately 190 cases have been settled while another 100 are in various stages of settlement.

At issue in the lawsuits is whether or not Paxil caused the birth defects of infants whose mothers took the antidepressant while pregnant. Scientific studies concerning the link between Paxil and other selective serotonin reuptake inhibitors (SSRIs) to birth defects have returned mixed results. Further studies have suggested a link between SSRIs and behavioral problems, withdrawal symptoms and developmental delays.

GlaxoSmithKline, however, has defended its drug and its own actions regarding Paxil. A spokeswoman for GlaxoSmithKline, Sarah Alspach, said in an e-mail statement that the company agreed to settle to avoid the costs and uncertainties of ongoing litigation

"GSK believes it acted properly and responsibly in conducting its clinical trial program for Paxil, in marketing the medicine, in monitoring its safety once it was approved for use and in updating pregnancy information in the medicine's label as new information became available," Alspach wrote, as published in the Legal Intelligencer on 6/23/10.

Plaintiffs, however, disagree. They argue that GlaxoSmithKline failed to adequately warn physicians and patients about the risks of birth defects when babies are exposed to Paxil prior to birth. They allege those birth defects include Persistent Pulmonary Hypertension of the Newborn (PPHN) and atrial or septal defects—holes in the heart. (...)

Adverse drug reactions from psychotropic medicines in the paediatric population: analysis of reports to the Danish Medicines Agency over a decade (Uheldige legemiddelreaksjoner fra psykotrope medisiner i barnebefolkningen: analyser av rapporter til Lægemiddelstyrelsen i en tiårsperiode)
BMC Research Notes 2010, 3:176 (23 June)
(...) Background The prescribing of psychotropic medicines for the paediatric population is rapidly increasing. In attempts to curb the use of psychotropic medicine in the paediatric population, regulatory authorities have issued various warnings about risks associated with use of these products in childhood. Little evidence has been reported about the adverse drug reactions (ADRs) of these medicines in practice. As spontaneous reports are the main source for information about previously unknown ADRs, we analysed data submitted to a national ADR database. The objective was to characterise ADRs reported for psychotropic medicines in the Danish paediatric population over a decade. (...)

Konklusjon Det høye antall alvorlige ADRer (Adverse Drug Reactions) rapportert for psykotrope medisiner i barnbefolkningen bør skape bekymringer for helsepersonell og leger. Tatt i betraktning det høye antall fødselsdefekter som er rapportert bør større omsorg utvises når disse legemidler forskrives til gravide kvinner. (...) (Conclusion The high number of serious ADRs reported for psychotropic medicines in the paediatric population should be a concern for health care professionals and physicians. Considering the higher number of birth defects being reported greater care has to be given while prescribing these drugs for pregnant women.)

More Questions About Paxil Side Effects (Flere spørsmål om Seroxats (Paxils) sideeffekter)
lawyersandsettlements.com 29.5.2010
Chicago, IL: En ny artikkel i ScienceNews reiser spørsmål om risiko for Seroxats (Paxils) sideeffekter og fødselsdefekter hos barn eksponert for antidepressiva før fødselen. Artikkelen referer til studier som antyder udefinerbare forandringer i hjernene til babyer eksponert for antidepressiva av typen selektive serotoninreopptakshemmere (SSRIer). Seroxat (Paxil) er et av legemidlene i SSRI-klassen. (Chicago, IL: A new article in ScienceNews raises questions about the risk of Paxil side effects and Paxil birth defects in children exposed to the antidepressant prior to birth. The article cites studies that suggest subtle changes in the brains of babies exposed to Selective Serotonin Reuptake Inhibitor (SSRI) antidepressants. Paxil is one of the drugs in the SSRI class.)

According to the author of the ScienceNews (06/05/10) article, Susan Gaidos, studies conducted in the past few years indicate that mice and rats exposed to antidepressants either just before or just after birth grew up anxious and depressed. A more recent study, according to Gaidos, suggests that children exposed to antidepressants while in the womb are more likely to appear sad or withdrawn at three years old than those not exposed to antidepressants.

Serotonin is produced naturally in the brain and is released into the spaces between the person's neurons. The neuron that releases the serotonin then takes it back almost immediately. This is called reuptake. Selective Serotonin Reuptake Inhibitors work by preventing serotonin's reuptake. The longer serotonin remains in the space between neurons (known as the synapse), the better the person feels. People who are depressed may feel less so because the serotonin remains in the synapse for longer. (...)

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

Common antidepressants 'increase miscarriage risk' (Vanlige antidepressiva "øker risiko for abort")
telegraph.co.uk 1.6.2010
Taking common antidepressants while pregnant significantly increases the chances of suffering a miscarriage, a new study warns.

The risk rose by more than two thirds if expectant mothers were taking the drugs, researchers found.

Previous studies have also found a link between antidepressants and birth defects.(...)

Dr. Anick Berard, from the University of Montreal, who led the research, said: "These results, which suggest an overall class effect of selective serotonin re-uptake inhibitors, are highly robust given the large number of users studied.

Overall, the increased risk was 68 per cent. (...)

Antidepressants during pregnancy increase risk of sponaneous abortion, study finds (Antidepressiva i løpet av svangerskapet øker risikoen for spontanaborter, ifølge studie)
latimes.com 31.5.2010
(...) In the new study, Dr. Anick Berard, director of the University of Montreal's Research Unit on Medications and Pregnancy at University Hospital Center Sainte-Justine used information from the Quebec Pregnancy Registry to identify 5,124 women who had a spontaneous abortions between 1998 and 2003 -- before warnings about the risks of the drugs became more common -- and compared them with about 10 times that many carefully matched women who did not have abortions. A separate database provided information about prescriptions the women had filled.

The researchers reported in the Canadian Medical Assn. Journal that 5.5% of the women who had spontaneous abortions had taken antidepressants, compared with 2.7% of those who did not have a spontaneous abortion. Controlling for other factors, that amounted to a 68% increase in risk. The biggest effects were found with paroxetine (brand names Paxil and Seroxat) and venlafaxine (Effexor) or when combinations of drugs from different families were used. (...)

Use of Antidepressants, Nicotine in Pregnancy Linked to Childhood Difficulties (Bruk av antidepressiva, nikotin i svangerskapet linket til vanskeligheter i barndommen)
medscape.com 10.5.2010
May 4, 2010 — Prenatal nicotine exposure may increase the risk of sleep problems in children through adolescence, whereas prenatal exposure to selective serotonin reuptake inhibitors (SSRIs) may increase the risk of behavior problems at the age of 3 years, although the risk may be moderated by the serotonin transporter promoter gene, SLC6A4.

These are the findings of 2 studies appearing in the May issue of Archives of Pediatrics and Adolescent Medicine.
These 2 studies, note the coauthors of an accompanying editorial, focus on compounds that are "at the eye of the storm of current concerns" regarding potential adverse effects of drug and chemical exposure on the developing fetus.

"In both instances, the new studies offer refined methods to further our understanding of these complex questions," write Gideon Koren, MD, and Irena Nulman, MD, of the Division of Clinical Pharmacology, Hospital for Sick Children, Toronto, Ontario, Canada. (...)

Antidepressant tied to risk of newborn heart defect (Antidepressiva knyttet til risiko for hjertedefekter hos nyfødte)
reuters.com 4.5.2010
NEW YORK (Reuters Health) - Women who use the antidepressant bupropion during early pregnancy may have an increased risk of having a baby with a particular type of heart defect, a new study suggests.

Researchers caution that it is not clear whether the medication, marketed as Wellbutrin, is the cause. And even if it is, they say, the absolute risk of the heart defect would be small -- affecting just 2 out of every 1,000 infants born to women who used bupropion during the first trimester.
But the findings, published in the American Journal of Obstetrics & Gynecology, do add to questions about the risks of using antidepressants during early pregnancy.

Some studies have already linked other antidepressants -- including some of the commonly used selective serotonin reuptake inhibitors (SSRIs) -- to higher-than-average, though small, risks of certain birth defects.

A study last year, for example, found that among nearly half a million Danish children born between 1996 and 2003, the risk of heart defects was elevated among those whose mothers had used SSRIs such as fluoxetine (Prozac), sertraline (Zoloft) and citalopram (Celexa) during early pregnancy. (...)

Antidepressants May Impact Infant Development (Antidepressiva kan ha følger for spedbarns utvikling)
lawyersandsettlements.com 28.2.2010
Denmark: A new study suggests that babies who are exposed to antidepressants prior to birth are slower to reach certain developmental milestones. The study will likely add to the growing controversy about whether or not SSRI antidepressants are safe for pregnant women to use. (...)

Mom's Antidepressant Use May Delay Baby's Development
depression.about.com 26.2.2010
If a mother takes an antidepressant during pregnancy, her child may experience delays in certain aspect of his development, according to Dr. Lars Henning Pederson and his research team at Aarhus University Hospital in Denmark.

Pederson's team identified 400 women who had taken antidepressants during pregnancy, as well as 500 women who were depressed but took no medication. Based upon the women's own reports, they then compared how many children hit specific developmental milestones - such as sitting up, following the direction of sounds with their eyes, expressing irritation and walking. (...)

Glaxo Said to Have Paid $1 Billion in Paxil Suits (Update2) (Glaxo hevdes å ha betalt 1 milliard dollar i forbindelse med Seroxat-søksmål)
Bloomberg.com 14.12.2009
Dec. 14 (Bloomberg) -- GlaxoSmithKline Plc has paid almost $1 billion to resolve lawsuits over Paxil since it introduced the antidepressant in 1993, including about $390 million for suicides or attempted suicides said to be linked to the drug, according to court records and people familiar with the cases.

As part of the total, Glaxo, the U.K.’s largest drugmaker, so far has paid $200 million to settle Paxil addiction and birth-defect cases and $400 million to end antitrust, fraud and design claims, according to the people and court records.

The $1 billion “would be worse than many people are expecting,” said Navid Malik, an analyst at Matrix Corporate Capital in London. “I don’t think this is within the boundaries of current assumptions for analysts.” (...)

GlaxoSmithKline Reportedly Paid $1 Billion for Paxil Lawsuits (GlaxoSmithKline har angivelig betalt én milliard dollar for Seroxat-søksmål)
lawyersandsettlements.com 14.12.2009
Philadelphia, PA: According to reports, Paxil-maker GlaxoSmithKline may have paid almost $1 billion to settle Paxil lawsuits alleging serious side effects, including birth defects, addiction and suicides or attempted suicides. (...)

With 600 birth defects lawsuits still waiting in the wings, a $2.5 million settlement for each lawsuit could leave GlaxoSmithKline on the hook for $1.5 billion in birth defect lawsuits alone.

According to Bloomberg, approximately 150 suicide-related lawsuits were settled for an average of $2 million and 300 suicide attempt cases were settled for an average of $300,000. Meanwhile, 10 birth defect lawsuits were settled for an average of $4 million. (...)

GSK to Pay $2.5 Million to Family in Birth Defects Lawsuit (GSK betaler 2,5 millioner dollar til familie for Seroxat-fødselsdefekter)
lawyersandsettlements.com 13.10.2009
(...) Interne GSK-e-poster indikerer at de visste (Internal GSK Emails Suggest They Knew)

Under rettssaken ba dommeren GSK om å overlevere e-poster skrevet av GSK-ledere, og en slik e-post, et notat skrevet av Bonnie Rossello i 1997, som var spesielt belastende, inneholdt uttalelsen, "Dersom negative, resultater kan begraves." Rosello refererte til hva den farmasøytiske giganten burde gjøre dersom det ble nødvendig å utføre dyrestudier på Seroxat (Paxil), kjent som paroxetine (paroksetin). Ifølge resultater utført av danske utviklere av den kjemiske forbindelsen, tok lave doser av paroxetine livet av unge rotter. (During the court case the judge ordered GSK to hand over emails written by GSK executives, and one such email, written by Bonnie Rossello in a 1997 memo, was particularly incriminating, including the statement, "If neg, results can bury." Rosello was referring to what action the pharmaceutical giant should take if it became necessary to do animal studies with Paxil, known generically as paroxetine. According to results of a study done by the Danish developers of the compound, low-dose paroxetine killed young rats.)

Under rettssaken, fortalte Tracey jurymedlemmene at Food and Drug Administration (FDA) ikke ba om ytterligere sikkerhetsstudier for selektive serotoninreopptakshemmere (SSRIer) - den klasse antidepressiva som Seroxat tilhører - før i 2003. På dette tidspunkt erkjente angivelig GSK at Seroxat var assosiert med en økt risiko for fødselsdefekter. (...) (During the trial, Tracey reportedly told jurors that the Food and Drug Administration (FDA) did not order additional safety studies on selective serotonin reuptake inhibitors (SSRIs)- the class of antidepressants to which Paxil belongs - until 2003. At that point, GSK allegedly acknowledged there was an increased risk of birth defects associated with Paxil.)

Selective serotonin reuptake inhibitors in pregnancy and congenital malformations: population based cohort study (Selektive serotoninreopptakshemmere i svangerskap og medfødte misdannelser: befolkningsbasert kohortstudie)
BMJ 2009;339:b3569 (23 September)
(...) Konklusjon Der er en økt forekomst av defekter i hjerteskillevegger hos barn av mødre forskrevet SSRI tidlig i svangerskapet, spesielt sertraline og citalopram. Den sterkeste forbindelsen ble påvist hos barn av kvinner som innløste forskrivninger på mer enn én type SSRI. (...) (Conclusion There is an increased prevalence of septal heart defects among children whose mothers were prescribed an SSRI in early pregnancy, particularly sertraline and citalopram. The largest association was found for children of women who redeemed prescriptions for more than one type of SSRI.)

(Anm: Antidepressiva (REM-søvn). (mintankesmie.no).)

(Anm: Fosterskader (legemiddelinduserte) (mintankesmie.no).)

Selective serotonin reuptake inhibitors and congenital malformations
Editorials
BMJ 2009;339:b3525 (23 September)
(...) In the linked population based cohort study from Denmark (doi:10.1136/bmj.b3569), Pedersen and colleagues confirm a previously reported doubling of risk for septal heart defects after early exposure in pregnancy to SSRIs (odds ratio 1.99, 95% confidence interval 1.12 to 3.53).⁴ (...)

Lack of consistency across these studies with respect to specific malformations and specific drugs makes it difficult to translate the findings into clinical practice. (...)

One explanation for this inconsistency, assuming that SSRIs do cause specific birth defects, is differences in study designs. For example, although Pedersen and colleagues linked records for 496 881 singleton live born infants, they identified only 1370 mothers who redeemed multiple prescriptions for an SSRI in the perinatal period. Therefore, the study may have been insufficiently powered to detect the previously suggested twofold to threefold increased risk for anencephaly, omphalocele, craniosynostosis, or right ventricular outflow tract defects, all of which occur at least an order of magnitude less frequently than septal defects. (...)

Strong Link Found Between Two Antidepressants and Infant Heart Problems (Sterk link funnet mellom to antidepressiva og spedbarns hjerteproblemer)
depression.about.com 25.11.2008
Women who took the antidepressants Prozac (fluoxetine) or Paxil (paroxetine) in their first trimester were significantly more likely to give birth to babies with heart problems than women who did not take them, according to a new study published in the November issue of the British Journal of Clinical Pharmacology. (...)

(Anm: British Journal of Clinical Pharmacology. Paroxetine and fluoxetine in pregnancy: a prospective, multicentre, controlled, observational study 2008;66: 695-705.)

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

ANTIDEPRESSANTS MAKE FOR SAD FISH (Antidepressiva bidrar til trist fisk)
SCIENCENEWS.ORG 25.11.2008
The drugs are becoming more common in river waters and can play dangerous head games with fish

UBEKVEM POSITUR Noen stripede hybride abborer utsatt for Prozac begynte til slutt å henge vertikalt i vannet — en høyst avvikende stilling — og sluttet å spise. (...) (AWKWARD POSE Some hybrid striped bass exposed to Prozac eventually began hanging vertically in the water — a highly anomalous pose — and stopped eating.)

Tons of medicine ends up in the environment each year. Much has been excreted by patients. Leftover pills may also have been flushed down the toilet. Because water treatment plants were never designed to remove pharmaceuticals, water released into rivers by these plants generally carries a broad and diverse array of drug residues.

In 2006, a pair of chemists reported that antidepressants downstream of water treatment plants were making it into the brains of fish. (...)

Soldater dør og ikke bare grunnet våpen

Soldiers are dying and not just from guns (Soldater dør og ikke bare grunnet våpen)
romeobserver.com 3.6.2010
(...) When soldiers return from Iraq or Afghanistan, and they have suffered either emotional or physical wounds, especially Traumatic Brain Injury (TBI), they are sent to Warrior Transition Units (WTU’s). Some shocking news has come to light concerning the large numbers of deaths in these WTU’s. For example, an article in the Chicago Tribune in February of 2008 has the Army Surgeon General stating that there has been a "series, a sequence of deaths" in the WTU’s. Many of these deaths were attributed to suicide, but an Army Times article which appeared in April of this year stated that "more than 70 soldiers died while assigned to the 36 WTU’s," but that "suicide is not the major cause of death." That honor belongs to something being referred to as "sudden cardiac arrest." Now, these soldiers may be as young as 20, so we would not expect to see this rate of cardiac arrest in those so young. What is going on? And, further, the wife of a veteran did some basic research and found that 128 veterans had died under similarly strange circumstances, such as "in barracks," "at work station," and none of them were found in a coma. They simply dropped dead.

For some insight into this horrible phenomenon, we can turn to the musings of another psychiatrist, Grace Jackson, who is distinguished in the field of psychopharmatoxicology, or, the ability of psychiatric drugs to poison those who take them. In studying these military deaths, Dr. Jackson has come up with several hypotheses as to the mechanisms of action. Her theories are quite complicated and technical, but I will try to sum them up.

• The psychiatric drugs these soldiers were taking, many of them involving the neurotransmitter serotonin, could have caused a massive dysregulation of the autonomic nervous system, which, by the way, is a possible explanation for Sudden Infant Death Syndrome.

• Legemidler som Seroquel og Seroxat (Paxil) kan ha fremtvunget uoppdagede hjernestammeeffekter, slik som slag, anfall eller forstyrrelser i hjerneaktivitet. (The drugs Seroquel and Paxil may have precipitated undetected brainstem effects, such as stroke, seizure or other disruption of brain activity.)

• Those soldiers with TBI may have sustained endocrine anomalies associated with pituitary damage, and drugs such as Seroquel and Paxil exacerbate these pre-existing deficiencies. These drugs could contribute to sudden cardiac death in these cases, as well.

• Sleep apnea is also associated with TBI (I can attest to this from personal experience counseling returning veterans: They ALL had sleep apnea!) The drugs the soldiers are receiving disrupt lung function, and disrupt the electrochemical processes of which contribute to regular sleep, and produce heart arrhythmia, leading to sudden cardiac death. (...)

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

Daily Mail: - Liv ødelegges av lykkepiller

Lives destroyed by happy pills: As our use of antidepressants DOUBLES in a decade, experts say thousands are being given dangerous drugs they don't need (Liv ødelegges av lykkepiller: Idet vårt forbruk av antidepressiva DOBLES på et tiår, sier eksperter at tusener er gitt legemidler de ikke trenger)
dailymail.co.uk 29.6.2010
(...) After about six weeks she went to see her doctor, who diagnosed depression and anxiety. 'I asked him if he was sure, because there were other symptoms such as diarrhoea, weight-loss and vomiting. But he confirmed his diagnosis and prescribed an antidepressant.' (...)

Unfortunately this only made her feel worse; she developed the shakes as well as suicidal thoughts. In an attempt to remedy this, her GP changed the medication three weeks later. But nothing changed.
And after mentioning her suicidal thoughts to her doctor, she was put under the supervision of a mental health team.

Six weeks later, Clare was put on yet another antidepressant, along with a tranquilliser and an anti-psychotic drug. She was now sleeping 14 hours a day; unable to work, she had to rely on her boyfriend for support.

'I was zombified, but still felt the anxiety and the terror, and that didn't seem right. However, my doctor simply increased my dose.' (...)

'The only good part was a brilliant nurse, who took me seriously when I said I'd always felt that something physical had caused my symptoms and put me in touch with a sympathetic private doctor,' she says.

A year-and-a-half after her symptoms began, Clare was diagnosed with an overactive thyroid and a problem with her adrenal glands. 'That was why I had been so bizarrely agitated, had diarrhoea and had lost weight.' (...)

Clare's story is extreme, but it is far from unique. Increasing numbers of Britons are taking antidepressant drugs, with prescriptions doubling over the past ten years, according to a report this month. In 2000, there were 20 million prescriptions - this rose to 39 million last year.

While this rise is partly being blamed on the recession, experts are concerned that misdiagnosis is a major factor. Indeed, a study published recently in The Lancet found that the average GP will wrongly diagnose 16 out of every 100 patients they see with depression and anxiety. (...)

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.)

- Antidepressiva linket til betydelig risiko for hjerneslag, fall og benbrudd

Antidepressants linked with significant risk of stroke and fracture (Antidepressiva linket til betydelig risiko for hjerneslag og benbrudd)
pulsetoday.co.uk 3.8.2010
Forskrivning av antidepressiva er assosiert med en betydelig økt risiko for slag, fall og benbrudd hos eldre pasienter ifølge analyser av data fra primærhelsetjenesten utført av britiske forskere. (Antidepressant prescribing is associated with a significantly increased risk of stroke, falls and fractures in older people, according to analyses of primary care data by UK researchers.)

Two analyses by the same team of researchers from the University of Nottingham of the QResearch database – a network of 602 practices in England – found antidepressants increased the stroke rate by up to half, the rate of falls by more than three quarters and the fracture rate by 87% compared with no antidepressant use.

Figures from the NHS information Centre show antidepressants are the 10th most commonly prescribed class of drugs in primary care, with 39 million prescriptions issued in England in 2009.

Although depression is common in older people, clinical trials for antidepressants often under-represent the elderly population so little is known about the risks of adverse events in older patients and the relative safety of individual drugs in this class. (...)

Serotonerg ubalanse? (Svindelen som aldri tar slutt)

Study Undermines Case For Antidepressants (Studie undergraver bevis for antidepressiva)
forbes.com 5.1.2010
(...) Såkalte selektive serotoninreopptakshemmere (SSRIer) slik som Seroxat, Prozac og Zoloft, er utstrakt brukt på bakgrunn av teorien om at deprimerte mennesker lider av mangel på hjernekjemikaliet serotonin. Men få harde data støtter det populære konseptet, ifølge Kirsch. "Hele idéen med serotoninmangel er en myte." (...) (So-called selective serotonin reuptake inhibitors such as Paxil, Prozac and Zoloft, gained widespread use on the theory that depressed people suffer from a deficit of the brain chemical serotonin. But little hard data supports the popular concept, Kirsch says. "This whole idea of serotonin deficiency is a myth.")

Det er ikke eksakt kjent hvor mange pasienter med mild depresjon som tar antidepressiva. Men en undersøkelse sitert av forskerne fant at 71 % av alle pasienter som søker behandling for depresjon faller i den mildere kategori, hvor det er sannsynlig at placebo virker like bra. (...) (It is unknown exactly how many patients taking antidepressants have milder cases of depression. But one survey cited by the researchers found that 71% of all patients seeking treatment for depression fall in the milder category, where placebos are likely to do as well.)

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

(Anm: Svindelen som aldri tar slutt (forskning.no 17.4.2004).)

(Anm: Antidepressant Drug Effects and Depression Severity A Patient-Level Meta-analysis. JAMA. 2010;303(1):47-53 (January 6).)

Ads for SSRI antidepressants are misleading, say researchers (Reklamer for SSRI-antidepressiva er villedende, ifølge forskere)
medicalnewstoday.com 12.11.2005
Reklamer for en klasse antidepressiva kalt SSRI-er påstår ofte at depresjon skyldes kjemisk ubalanse i hjerne, og at SSRI-er korrigerer denne ubalansen, men disse påstander er ikke støttet av vitenskapelig bevis, uttaler forskere i PLoS Medicine. (Consumer ads for a class of antidepressants called SSRIs often claim that depression is due to a chemical imbalance in the brain, and that SSRIs correct this imbalance, but these claims are not supported by scientific evidence, say researchers in PLoS Medicine.)

Selv om forskere på 1960-tallet antydet at depresjon kan være linket til lavt nivå av serotonin (den såkalte "serotonin-hypotese"), sier de at forskning hittil har mislykkes å bekrefte hypotesen. (Although scientists in the 1960s suggested that depression may be linked to low brain levels of the chemical serotonin (the so-called "serotonin hypothesis"), contemporary research has failed to confirm the hypothesis, they say.)

Forskerne--Jeffrey Lacasse, doktorgradkandidat Florida State University og dr. Jonathan Leo, professor i neuroanatomi ved Lake Erie College of Osteopathic Medicine--gransket amerikansk forbrukerreklame for SSRI-er publisert i trykte medier, fjernsyn, og internett. De fant mange påstander om at SSRI-er gjenoppretter serotoninbalansei hjernen. "Men likevel er der ikke etablert noe vitenskapelig som tilsier at "balanse" av serotonin korrigeres," ifølge forfatterne. (...) (The researchers--Jeffrey Lacasse, a doctoral candidate at Florida State University and Dr. Jonathan Leo, a neuroanatomy professor at Lake Erie College of Osteopathic Medicine--studied US consumer advertisements for SSRIs from print, television, and the Internet. They found widespread claims that SSRIs restore the serotonin balance of the brain. "Yet there is no such thing as a scientifically established correct 'balance' of serotonin," the authors say.)

(Anm: Serotonin and Depression: A Disconnect between the Advertisements and the Scientific. PLoS Medicine 2005;2:0101-0106 (December 2005). (PDF).)

Debate Simmers Over Popular Antidepressant Ad Claims (healingwell.com) (Debatten koker grunnet reklamepåstander om populær antidepressiva)
healthfinder.gov 28.2.2006
Der er ingen bevis for at depresjon stammer fra en kjemisk ubalanse i hjernen, hevder kritikere. (There's no evidence depression stems from a chemical imbalance in the brain, critics say.)

-- Mange amerikanere har sett TV-reklamer for Pfizers reseptbelagte antidepressiva Zoloft. (...) (-- Many Americans have seen the television ad for Pfizer Inc.'s prescription antidepressant Zoloft.)

Denne type utsagn er formidlet i reklamekampanjer så ofte overfor forbrukere av selektive serotoninreopptakshemmere (SSRI) at kritikere sier at disse påstander nå tilsynelatende oppfattes som en slags vitenskapelig sannhet. (Statements like these have been repeated so often in direct-to-consumer ad campaigns for selective serotonin reuptake inhibitor (SSRI) antidepressants that critics say they now have the ring of scientific truth.)

Derfor kan mange amerikanere "bli svært overrasket over at ikke en eneste artikkel kan fremvises som direkte påviser at depresjon er et resultat av mangel på serotonin," sa Jeffrey Lacasse, en doktorgradsstudent ved Florida State University's College of Social Work. (...) (That's why many Americans "might be particularly surprised that not a single article can be produced which directly demonstrates that depression is the result of a serotonin deficiency," said Jeffrey Lacasse, a doctoral student at Florida State University's College of Social Work.)

New Strategy For Developing Antidepressants
medicalnewstoday.com 10.12.2007
Researchers may be able to develop an antidepressant which takes effect almost immediately by directly targeting novel molecules in the brain instead of taking a less direct route, which can lead to longer times for medication to take effect, according to a new study presented at the American College of Neuropsychopharmacology (ACNP) annual meeting. The antidepressant is also thought to be effective in people for whom previous treatments have been ineffective. This human and rodent research is among the first to examine the effects of rapid antidepressant strategies. (...)

Onset of action of antidepressants
BMJ 2007;334:911-912 (5 May)
(...) A meta-analysis of 76 double blind placebo controlled trials of antidepressant treatment for depression in 2005 found that 60% of overall improvement occurred during the first two weeks and that half of all patients who respond to a six week trial respond in the same period.¹⁰ More recently, a meta-analysis of placebo controlled trials of selective serotonin reuptake inhibitors suggested that therapeutic response is greatest in the first week, with a gradual decline in the size of benefit over successive weeks of treatment.¹¹ One third of the total effect seen at six weeks was apparent in the first week.¹¹ As the studies were placebo controlled trials, this improvement was unlikely to be a placebo effect. (...)

Widow to testify at Senate committee hearing on drug safety
expertclick.com 14.3.2007
Kim's husband, Timothy (Woody) Witczak, was a 37-year-old dynamic and upbeat, happily married man who was prescribed Zoloft because he was having difficulty sleeping due to job-related stress. He was on Zoloft for about five weeks with an increased dose before he committed suicide (by hanging himself from the rafters in his garage). He had no history of mental illness or suicidality.

His symptoms after Zoloft and before his death included profuse sweating, worsened insomnia, horrible nightmares, headaches, agitation and an odd feeling in his head (he told his wife that he felt like his head was "detached from [his] body.") This phenomenon has been acknowledged by Pfizer in internal company documents to be a side effect of Zoloft.

Kim Witczak has become an influential victim advocate for drug safety. As a result of Woody’s death, Kim established www.woodymatters.com. The website serves as an information clearing house on antidepressant risks and a forum for other victims. FDA reform has become an increasingly important goal of woodymatters.com. Kim has traveled to Washington D.C. over 20 times to advocate for antidepressant warnings as well as FDA reform. Kim has, on numerous occasions, testified before the FDA, US Congress, and Minnesota legislature concerning these issues. Kim’s story has been featured in a number of news reports, including the November 2005 issue of Fortune Magazine and in an I-Team feature on WCCO TV in Minneapolis. She has also been on NPR regarding drug advertising.

See: WCCO TV I-Team Report: www.wcco.com/iteam/local_story_142142535.html
Star Tribune article “The Battle for Woody”: www.baumhedlundlaw.com/media/ssri/Zoloft/Witczak/Battle-for-Woody.pdf (...)

SSRIs start to relieve depression soon after the start of treatment
BMJ 2006;333 (9 December)
Abstract
Research question Do selective serotonin reuptake inhibitors take weeks to work?

Answer Probably not. Symptoms of depression improve during the first week of treatment (...)

UM study links genetic mutations to depression
sun-sentinel.com 26.9.2006
University of Miami researchers reported new evidence Monday that clinical depression appears to be caused by inborn genetic mutations. (...)

New Depression Findings Could Alter Treatments
nytimes.com 8.8.2006
The results of two new studies may signal a substantial shift in the way psychiatrists and researchers think about treatment for severely depressed patients. (...)

Clinical & Research News Brain Protein Could Be Treatment Breakthrough
Psychiatr News 2006;41:45 (April 21)
American Psychiatric Association
The finding that substance P is implicated in depression and posttraumatic stress disorder should boost efforts to see whether substance P antagonists can counter the disorders.

It looks as though a small protein discovered in horses' brains 75 years ago, and since dubbed substance P, may play a role in depression and posttraumatic stress disorder (PTSD). (...)

Hjerneskader årsag til depression
netdoktor.com 7.4.2006
Er man over 50 år og får sin første depression, kan det skyldes blodpropper i hjernen. Delresultater fra et forskningsprojekt under den nyoprettede neuropsykiatriske enhed i Risskov viser nemlig, at fire ud af ti patienter har læsioner i hjernen.

Hjerneskader og depressioner ser derfor ud til at være tæt forbundet, men det er svært at sige, hvad der opstår først. Overlæge Poul Videbech fra Center for Psykiatrisk Grundforskning håber, at den nye viden fra undersøgelsen kan være med til at fjerne det sociale stigma ved depression.

Formålet med undersøgelsen er at fastslå årsagen til hjerneskaderne og at forhindre, at de udvikler sig og forårsager demens. (...)

Depression kan måles i hjernen
netdoktor.com 20.10.2005
Depression kan måles i hjernen, da den ser anderledes ud hos personer, der lider af en svær depression end hos raske personer.

Depressive personer har nemlig en væsentligt forhøjet blodgennemstrømning i hippocampus området i hjernen. Det område har blandt andet betydning for følelser, drifter og hukommelse ligesom det regulerer kroppens respons på stress.

Det viser en ny stor undersøgelse af deprimerede patienters hjerner fra Center for Psykiatrisk Grundforskning i Århus. Man undersøgte 42 svært deprimerede og 47 raske personer med både PET- og MR-scanninger af hjernen kombineret med psykologiske test.

”For patienterne vægter det tungt, at vi er i stand til at finde noget i hjernen, som er anderledes end hos raske mennesker. Depression er jo en sygdom, som stadig er forbundet med skyld og skam”, siger overlæge Poul Videbech, der har stået i spidsen for forskningen.

Undersøgelsen bliver præsenteret i en doktorafhandling ved Århus Universitet fredag den 21. oktober. (...)

Mulig granskning av GSK/Seroxat

GlaxoSmithKline faces US scrutiny over Paxil suicide link (GlaxoSmithKline står overfor amerikansk granskning av Seroxats selvmordslink)
guardian.co.uk 12.6.2008
(...) The senator also pointed to a report recently unsealed by a US court that found GSK knew as early as 1989 that Paxil carried a heightened suicide risk in adults as well as children.

The report, by Harvard University psychiatrist Joseph Glenmullen, was based on internal GSK documents and intended for use in ongoing US court cases against the company. (...)

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

(Anm: Grassley seeks FDA scrutiny of Paxil and suicide risk (finance.senate.gov).

(Anm: Sen Grassley investigates GlaxoSmithKline and Paxil/Seroxat (seroxatsecrets.wordpress.com).)

Parlamentsmedlem kritiserer legemidler under avhør om dødsårsak

MP takes war on drugs to inquest (Parlamentsmedlem kritiserer legemidler under avhør om dødsårsak)
torontosun.com 18.6.2010
Oakville MP Terence Young started a relentless campaign to prevent tragedies linked to prescription drugs when his teenaged daughter died after taking a since-banned drug Prepulsid for bloating in 2000.

He used a coroner’s inquest Friday to champion a host of changes aimed at protecting Canadians by making them aware of the dangerous side effects of prescription drugs.

The 57-year-old MP testified at the inquest examining the May 6, 2007 suicide of athlete-scholar Sara Carlin after the 18-year-old took an anti-depressant drug called Paxil.

Her parents are blaming the drug for her death.

Sara hanged herself in the basement of her parents’ Oakville home after taking Paxil for 14 months.

Young emphasized that patients must be educated about the dangerous side effects of drugs and the possibility of using alternate non-drug treatments. (...)

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

The National Association for Premenstrual Syndrome (NAPS)

Drug warning for PMT sufferers (Legemiddeladvarsel for PMS-pasienter)
bbc.co.uk 18.6.2008
Many young women are being told they are experiencing depression
There's been a rise in the number of young women being told they've got depression, when they're actually experiencing hormonal problems, according to the only UK-wide charity for people with PMT.

National Association for Premenstrual Syndrome (NAPS) opplyser at flere og flere kvinner kontakter dem fordi de anser at de feilaktig er blitt forskrevet antidepressiva inklusive Prozac og Seroxat. (...) (The National Association for Premenstrual Syndrome (NAPS) says more and more women are contacting them because they reckon they've wrongly been prescribed anti-depressants including Prozac and Seroxat.)

(Anm: National Association for Premenstrual Syndrome (NAPS).)

Antidepressiva ødelegger ansiktsmuskulatur, og gir økt aldring

Divorce, Antidepressants, Or Weight Gain/Loss Can Add Years To Your Face (Skilsmisse, antidepressiva, eller vektøkning/vekttap kan legge år til ditt ansikt)
medpagetoday.com 4.2.2009
Your mother's wrinkles -- or lack there of, may not be the best predictor of how you'll age. In fact, a new study claims just the opposite. The study, involving identical twins, suggests that despite genetic make-up, certain environmental factors can add years to a person's perceived age. Results just published on the web-based version of Plastic and Reconstructive Surgery(R), the official medical journal of the American Society of Plastic Surgeons (ASPS), reveal that factors like divorce or the use of antidepressants are the real culprits that can wreak havoc on one's face. (...)

During the study, Dr. Guyuron and his colleagues obtained comprehensive questionnaires and digital images from 186 pairs of identical twins. The images were reviewed by an independent panel, which then recorded the perceived age difference between the siblings.

Results showed that twins who had been divorced appeared nearly 2 years older than their siblings who were married, single or even widowed. Antidepressant use was associated with a significantly older appearance and researchers also found that weight played a major factor too. In those sets of twins who were less than 40 years old, the heavier twin was perceived as being older, while in those groups over 40 years old, the heavier twin appeared younger. (...)

Additionally, researchers suspect that continued relaxation of the facial muscles due to antidepressant use, could account for sagging. (...) (I tillegg mistenker forskerne at den vedvarende avslapping av ansikstmuskler som antidepressiva forårsaker, kan forklare årsaken til at ansiktet faller sammen (henger).)

(Anm: Plastic and Reconstructive Surgery. Factors Contributing to the Facial Aging of Identical Twins (Note: This study is appearing in a raw, publish-ahead-of-print format and will be published in final form in the April 2009 issue of PRS.) (February 2009).)

Trikset for å unngå rynker
dinside.no 4.2.2009
Forskning viser at du selv kan påvirke.

Det er langt fra bare alder og genetiske faktorer som avgjør om du blir rynkete i ansiktet. Det kommer fram i en fersk studie publisert i tidsskriftet Plastic and Reconstructive Surgery. (...)

Stress er synderen
Testpersoner som hadde brukt antidepressiva eller som hadde gått kraftig opp og ned i vekt også så eldre ut enn tvillingen sin. (...)

Antidepressiva kan dessuten føre til at ansiktshuden henger mer, fordi medisinen gjør at ansiktsmuskulaturen blir mer avslappet. (...)

What happens when minnows take a chill pill? (Hva skjer når småfisk tar en avslapningspille)
startribune.com 22.12.2008
Meghan McGee, a graduate student at St. Cloud State University, tested minnow larvae reaction time to vibrating movement.

St. Cloud State University research found that minnows exposed to antidepressants, whose residues end up in local waters, are more laid back - which is not so great for survival. (...)

FIKK 2,2 MILL. etter ansiktskramper (PDF)
Av JORUN SOFIE F. AARTUN og MAY LINN GJERDING
VG 22.05.2006 (Side: 9. Emne: Helse. Kategori: HELSE OG MEDISIN)
En 51 år gammel kvinne fikk utbetalt hele 2,2 millioner kroner i erstatning, etter at «lykkepiller» ga henne kroniske rykninger i ansiktet. Informasjonssjef Torill Svoldal Stæhr i Norsk Pasientskadeerstatning (NPE) ser svært alvorlig på saken.

- Kvinnen har fått store skader. I tillegg til de kroniske muskeltrekningene i ansikt, hals og mellomgulv har kvinnen store pustebesvær, sier Svoldal Stæhr i NPE.

Hun mener det er overveiende sannsynlig at kvinnen fikk de lumske skadene som følge av såkalte SSRI-preparater, som «lykkepillene» heter på fagspråket.

- Store smerter
- Kvinnen har store smerter og er delvis eller helt ufør etter å ha tatt preparatet Fontex, sier Svoldal Stæhr.

Fontex, bedre kjent som Prozac, skal virke mot depresjon, angst, spiseforstyrrelser, narkolepsi og andre psykiske lidelser.

Det foreligger en potensiell risiko for kramper ved behandling med antidepressive legemidler. (...)

Antidepressiva kan øke risiko for hjertedød

Psychiatric Drugs Might Raise Cardiac Death Risk (Psykiatriske legemidler kan øke risiko for hjertedød)
healthfinder.gov 14.5.2009
But other medical factors could also be at play, researchers note. (...)

The study doesn't reveal specifically which psychiatric drugs were examined, but it does say that those who died of cardiac death were more likely to have taken one of three types.

Almost 11 percent of those who suffered sudden cardiac death took antipsychotics, compared to 1.4 percent of those who survived heart attacks.

The numbers for antidepressants were 7.4 percent and 3 percent, respectively, and 18.4 percent and 5 percent for benzodiazepines, which include drugs such as Xanax. (...)

Antidepressiva kan skade mange menneskers sexliv

New targets for old drugs
Nature 2009 doi:10.1038/news.2009.1047 (1 November)
A computer program predicts thousands of previously unknown drug-target associations. (...)

For example, the antidepressants Prozac and Paxil, which work by boosting serotonin levels in the brain, also bound the β-adrenergic receptors, the researchers showed. This β-blocking activity could explain some of the drugs' side effects which include nausea and decreased libido.

Trip or treatment?
"The pharmaceutical industry should take note of this work," says Jeremy Jenkins, a chemoinformatician at the Novartis Institutes for BioMedical Research — the drug company's research arm — in Cambridge, Massachusetts, who was not involved in the new work. "This could really help us improve on preventing safety issues, which are one of the major contributors to drugs failing." (...)

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

Sex and Psych Drugs - Young Couples Beware
By Evelyn Pringle
lawyersandsettlements.com 2.6.2009
Although the adverse effects of women taking psychiatric drugs while pregnant related to birth defects and infant withdrawal syndrome are often discussed or reported, the serious adverse effects on the sex lives and reproductive systems of millions of young couples are rarely mentioned.

Whatever the reason, due to the ever widening marketing campaigns by the psycho-pharmaceutical industry, young people need to be warned before they get conned into taking psychiatric drugs.

Sexual dysfunction, including lack of libido, orgasmic dysfunction and delayed ejaculation, are common side effects of using SSRI antidepressants, according to the May 2005 report, “The Marketing of Depression: The Prescribing of SSRI Antidepressants to Women,” by Dr Janet Currie. The report warns:

“There are concerns that not all sexual dysfunction may fully resolve after termination of treatment. Since SSRIs are prescribed more often for women, women are more frequently affected by SSRI-induced sexual dysfunction. Because SSRIs can also lead to a worsening of depression, paradoxical effects, emotional blunting or detachment, reduced emotional activity, memory loss and confusion, these effects, in conjunction with sexual dysfunction, can negatively affect intimate relationships.” (...)

Antidepressants may damage more sex lives (Antidepressiva kan skade mange menneskers sexliv)
boston.com 15.12.2008
Sexual "numbness." Lack of libido. Arousal that stalls. (...)

Current warnings on the labels of selective serotonin reuptake inhibitors, or SSRIs, cite early studies in which the prevalence of sexual side effects was lower: 4 percent for Prozac, for example, and ranging from 0 to 28 percent for Paxil.

But more recent studies, in which patients were more likely to be asked about specific sexual side effects and thus more likely to report them, suggest that the ballpark range of those affected by SSRIs is between 30 percent and 50 percent, said researchers including Dr. Richard Balon, a psychiatry professor at Wayne State University who studies the symptoms.

That would translate into millions of affected sex lives among the estimated 1 in 8 American adults who have tried these antidepressants in the past decade or so. Some studies have found the range still higher. (...)

Balon and other researchers agree that the issue is complex and the science imperfect: Mental illness can often impair sexuality, and the studies on SSRI-related sexual dysfunction have been small. "The [pharmaceutical] industry, understandably, has no interest in funding this," Balon noted. (...)

For example, Dr. Cigdem Tanrikut a Massachusetts General Hospital urologist, reported last month at the annual meeting of the American Society for Reproductive Medicine that when 35 normal, healthy men were put on Paxil for five weeks, up to 35 percent of them reported new problems with erections and up to 47 percent reported difficulty ejaculating while on the medication. (...)

But in a small number of patients, it appears, the symptoms continue after stopping the drugs. Based on recent case reports of persistent effects, an article earlier this year in the Journal of Sexual Medicine said patients should "be told that in an unknown number of cases, the side effects may not resolve with cessation of the medication." (...)

Legger antidepressiva en demper på kjærlighetslivet?

Sexgale ældre bliver kastreret med lykkepiller
bt.dk 9.3.2008
Gamle kan være så demente, at de mister hæmningerne og får ustyrlig lyst til sex. Lægerne giver dem lykkepiller og anden medicin, som kan lægge låg på lysterne. (...)

(Anm: Effect of citalopram in treating hypersexuality in an Alzheimer's Disease case. Neurol Sci. 2008 Sep;29(4):269-70. Epub 2008 Sep 20.)

Dette dreper de unges sexlyst
dinside.no 5.5.2008
Hasj kan ødelegge sexlysten for unge.

Det er én ting som tar knekken på selv tenåringenes potens. (...)

- Mange som bruker hasj, blir sløve, tiltaksløse og får ikke hverdagen til å fungere, verken med jobb eller skole. Mange får etter hvert nedbrutt selvbilde, noe som kan resultere i depresjon og angst. At de som går på antidepressiva, også kan få potensproblemer, er noe vi kjenner til. Men dette er problemer som først kommer frem etter noen ganger med behandling, sier han. (...)

Are antidepressants taking the edge off love? (Legger antidepressiva en demper på kjærlighetslivet?)
latimes.com 30.7.2007
Sure, we know about the sexual side effects of SSRIs. But researchers now wonder if that's the only aspect of romance the drugs can influence. (...)

Any drug that has sexual side effects, Thomson says, could well blunt other chemicals the brain uses to intently focus on one person or to work up the obsession necessary to fall in love in the first place.

Then there was the 42-year-old single woman who had not been on a date in the eight years she had been taking an antidepressant. "She had not felt any desire [to date] for at least that period of time," he says. (...)

At that time, reports were that only about 6% of patients suffered sexual side effects, but the low rate is now understood to have resulted because doctors failed to ask questions about sex and patients were reluctant to bring it up. A later analysis put that figure at about 30%, and a 2001 study at as high as 73%. It is one of the top reasons that people stop taking the drugs. (...)

(Anm: Love is blue. (magicvalley.com 13.8.2007).)

5 Questions for 'Doctor of Love' Researcher Helen Fisher
popularmechanics.com 13.2.2008
(...) Are there certain advancements in, say, new drugs or antidepressants that can have an adverse on this quest you’re speaking about?
Yes. I think we’ve evolved through distinctly different brain systems involved for mating and reproducing. One is the sex drive, one is romantic love, and the third is attachment—that sends the sense of calm and security you can feel with a long-term partner. And when you take the serotonin-enhancing antidepressants like Prozac, Paxil, Zoloft, etc., what you’re doing is driving up serotonin in the brain, and we know that that affects the sex drive. In almost 75 percent of people it kills the sex drive. (...)

Paedophiles offered 'happy pills' to curb their sex drive (Pedofile tilbudt "lykkepiller" for å dempe sexlyst)
dailymail.co.uk 14.11.2007
Det er kommet frem at pedofile tilbys gratis Prozac som alternativ til "kjemisk kastraksjon". (Paedophiles are to be offered free Prozac as a softer alternative to 'chemical castration', it has emerged.)

The Government secured headlines this summer when it promised offenders would be given - on a voluntary basis - strong medication to curb their sex drive.

However, these drugs, which amount to chemical castration by making it difficult to have sex, have a number of side-effects which could deter potential users. (...)

Brain Chemical Could Spur Lovesickness
healthfinder.gov 15.10.2008
A monogamous rodent could shed light on romantic loss. (...)

Examination of the brains of the lovesick voles revealed heightened activity of a chemical messenger called corticotropin releasing factor (CRF) in an area of the hypothalamus, a center for emotions in the brain.

When the researchers administered a drug that blocked CRF activity, voles who'd been separated from their mate began to perform just as vigorously in the stress tests as all the other voles tested. It seemed the drug "switched off" the mechanism -- and their lovesickness, as well. (...)

(Anm: Pharmacologic differences among the SSRIs: focus on monoamine transporters and the HPA axis. CNS Spectr. 2004 Jun;9(6 Suppl 4):23-31.)

- Etter noen få måneder så skiftet rottene fra å være unormalt vennlige til å være mer antisosiale enn de var før de fikk midlet

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".)

SSRI-er utsetter utløsningen

Första läkemedlet mot för tidig utlösning godkänt
dagensmedicin.se 10.2.2009
Det första läkemedlet mot för tidig utlösning har godkänts i Sverige. Preparatet fördröjer utlösningen i mellan en och drygt två minuter.
Det nya läkemedlet ska säljas som tabletter under namnet Priligy och är godkänt på indikationen prematur ejakulation, för tidig sädesavgång. (...)

Ny pille utsetter utløsningen
Mari Rian Hanger
dagensmedisin.no 11.2.2009
Det første legemiddelet mot for tidlig utløsning er godkjent i Sverige. – Mange flere vil tørre å stå fram med problemet hvis dette blir godkjent i Norge, sier urolog Ole Martin Høeg. (...)

Ifølge det svenske Läkemedelsverket er den eneste dramatiske bivirkningen at det finnes en risiko for at følsomme personer svimer av på grunn av blodtrykksfall. (...)

(Anm: Priligy (Dapoxetine) (wikipedia.org).)

Antidepressiva kan skade menns sædceller (DNA)

Anti-depressants can damage men's sperm (Antidepressiva kan skade menns spermie)
chicagotribune.com 12.6.2009
Add anti-depressants to the list of substances that can damage men’s sperm and potentially impair their fertility.

In a new study, New York researchers report that as many as half of men taking the anti-depressant paroxetine (brand names, Seroxat and Paxil) have higher levels of sperm fragmentation.

The study was published online today by the journal Fertility & Sterility.

“It’s fairly well known that SSRI anti-depressants negatively impact erectile function and ejaculation. This study goes on step further, demonstrating that they can cause a major increase in genetic damage to sperm,” said Dr. Peter Schlegel, the study’s senior author and professor of reproductive medicine at Weill Cornell Medical College in New York.

“Although this study doesn’t look directly at fertility, we can infer that as many as half of men taking SSRIs have a reduced ability to conceive. These men should talk with their physicians about their treatment options,” he added. (...)

Dr. Cigdem Tanrikut speculated that the anti-depressant caused mens’ sperm to slow down as it makes its way through the male reproductive tract. Sperm gets “hung up,” she said in a statement, allowing it to age and become damaged.

The amount, concentration and motility of sperm were not significantly changed by the medication.

Though men may not know it, sperm can be damaged by various substances, including smoking, alcohol, heat, anabolic steroids, drug abuse, sexually transmitted diseases and some environmental exposures. (...)

Urovekkende dårlig sædkvalitet hos norske menn
aftenposten.no 22.6.2010
(...) Instituttet mener det er urovekkende at en av fem norske menn har en spermiekvalitet under grensen som Verdens Helseorganisasjon, WHO, mener er assosiert med redusert fruktbarhet. (...)

- Det er åpenbart at spermier kan ha DNA-skader som har stor betydning for både fertilitet og det fødte barnet, samtidig som slike skader kan være vanskelige å oppdage. Vi kjenner oftest ikke årsakene til at spermiene er skadet, sier avdelingsdirektør Gunnar Brunborg og stipendiat Ville Sipinen ved Folkehelseinstituttet. (...)

Adverse effect of paroxetine on sperm (Uheldig virkning av Seroxat (paroxetine) på sædceller)
Fertility and Sterility (American Society for Reproductive Medicine)
published online 10 June 2009.
Objective
To assess the effects of a selective serotonin reuptake inhibitor on semen parameters. (...)

Patient(s)
Thirty-five healthy male volunteers, 18–65 years old.
Intervention(s)
Paroxetine administration for 5 weeks. (...)

Conclusion(s)
In men with normal semen parameters, paroxetine induced abnormal sperm DNA fragmentation in a significant proportion of subjects, without a measurable effect on semen parameters. The fertility potential of a substantial number of men on paroxetine may be adversely affected by these changes in sperm DNA integrity. (...)

Anti-Depressant-Associated Changes In Semen Parameters
medpagetoday.com 28.11.2008
SAN FRANCISCO, CA, USA (UroToday.com) - The authors previously reported an effect of antidepressants on semen parameters. The current study was designed to assess/confirm their prior report of the effects of an SSRI, paroxetine (Paxil), on semen parameters. (...)

As opposed to prior report, semen parameters (volume, concentration, motility, morphology) were not significantly altered during SSRI treatment. However, mean DNA fragmentation TUNEL score was significantly higher on SSRI (30.3%) versus baseline (13.8%). Multivariate logistic regression, correcting for age and body mass index, confirmed that SSRI treatment was significantly correlated with increased DNA fragmentation Up to 35% of men noted significant changes in erectile function and up to 47% of subjects reported ejaculatory difficulties while on paroxetine. (...)

Svårare bli pappa med antidepressiva
sr.se 26.9.2008
(...) Antidepressiva läkemedel kan göra det svårare för män att få barn. Det tycks bero på att spermierna drabbas av skador i sitt DNA, visar en första, mindre undersökning från Cornell Medical Centre i New York. (...)

Paxil could make men infertile, researchers suggest (Seroxat kan gjøre menn sterile)
pharmatimes.com 25.9.2008
US scientists have claimed that one of the most commonly used selective serotonin re-uptake inhibitors, GlaxoSmithKline's Seroxat/Paxil, causes serious DNA damage in sperm cells, according to the report in New Scientist. (...)

Paxil could make men infertile, researchers suggest
pharmatimes.com 25.9.2008
US scientists have claimed that one of the most commonly used selective serotonin re-uptake inhibitors, GlaxoSmithKline's Seroxat/Paxil, causes serious DNA damage in sperm cells, according to the report in New Scientist. (...)

Antidepressants may damage male fertility: study (Antidepressiva kan skade menns fruktbarhet, ifølge studie)
reuters.com 24.9.2008
LONDON (Reuters) - Common antidepressant drugs may reduce some men's fertility by damaging the DNA in their sperm, according to scientists.

A study of 35 healthy men given paroxetine -- sold as Paxil or Seroxat by GlaxoSmithKline -- found that, on average, the proportion of sperm cells with fragmented DNA rose from 13.8 percent before treatment to 30.3 percent after just four weeks.

Similar levels of sperm DNA damage have been linked to problems with embryo viability in couples trying to have children. (...)

Allan Pacey, Senior Lecturer in Andrology at the University of Sheffield, said the apparent increase in sperm DNA damage was "alarming," although he noted the level at which damage becomes clinically significant was open to debate. (...)

Being Overweight Does Not Result In Decreased Sperm Production, Study Shows
sciencedaily.com 17.6.2008
(...) Santoro and her coworkers plan to further study a trend they saw toward reduced sperm motility in the six men who were taking an antidepressant in the selective serotonin reuptake inhibitor (SSRI) class. This class of drugs includes Prozac, Celexa, Lexapro, Paxil and Zoloft.

“We know that SSRIs affect sex drive, but there aren’t much data on their effect on fertility,” she said.

The results will be presented at The Endocrine Society’s 90th Annual Meeting in San Francisco. (...)

Antidepressants may make men infertile (Antidepressiva kan gjøre menn sterile)
guardian.co.uk 24.10.2006
Bestselling antidepressant drugs may be making some men infertile, research reported yesterday suggested.

The warning follows a study of two men at Cornell Medical Centre in New York whose sperm counts dropped to almost zero while taking the drugs but recovered to healthy levels whenever their medication was suspended.

The men were tested over a two-year period while being treated with the selective serotonin reuptake inhibitors (SSRIs) Citalopram (Cipramil) or Sertraline (Lustral), which belong to the same class of drugs as Prozac and Seroxat, Britain's biggest selling antidepressants. (...)

"These were men with normal sperm counts that went to nearly zero when they were on these antidepressants but returned to normal when they were off them," Prof Schlegel said.

"It's a dramatic effect and it has never been described before. We believe that while it has had a profound effect on these two men, it could be having a significant but more subtle effect on many more." (...)

Antidepressants Linked to Male Infertility
newsinferno.com 24.10.2006
Researchers at New York’s Cornell Medical Center have found a major correlation between use of antidepressants and sperm count. Men who take selective serotonin reuptake inhibitors (SSRIs) are being urged to consult closely with their doctors in order to determine a proper course of action in light of the new study, the first of its kind. Cornell’s Peter Schlegel announced the results this week at the 62nd annual meeting of the American Society for Reproductive Medicine (ASRM) in New Orleans. (...)

Dr. Schlegel believes that the problem may be connected to damage of the nerves in the vas deferens, the tube trusted with the task of delivering sperm to semen just before ejaculation. For male SSRI patients who may be considering starting or continuing a family, the results may have major ramifications. (...)

(Anm: vas deferens; ductus deferens; jf ev kongenital bilateralt manglande vas deferens EN vas deferens. Kilde: Norsk medisinsk ordbok.)

(Anm: vas deferens; wikipedia.org.)

Prozac is linked to low sperm count (Prozac linket til dårlig sædkvalitet)
timesonline.co.uk 24.10.2006
ANTIDEPRESSANT drugs could lower men’s sperm count, the first investigation of their effect on male fertility has found. (...)

SSRI-preparater og mulige MS-liknende hjerneskader

Antidepressant linked to worsening white matter in elderly (Antidepressiva linket til forverring av hvit substans hos eldre)
rehabpub.com/reuters_article.asp 17.3.2008
NEW YORK (Reuters Health) - The results of a study employing serial cranial MRI suggest that elderly adults who use tricyclic antidepressants may be at increased risk for progression of white matter lesions, which have been linked with late-life depression by previous studies. (...)

The use of an antidepressant from any class during the study period hastened the progression of white matter disease, according to the report in the March issue of Stroke.

Contrary to what the investigators had hypothesized, SSRI use did not reduce, but slightly increased the risk of worsening white matter on multivariate analysis. Still, the 36% increased risk seen with these agents was not statistically significant.

The use of a tricyclic antidepressant, however, was associated with a significantly elevated risk of worsening white matter lesions. Compared with those who used no antidepressants, patients receiving an agent in this drug class had an increased risk of 77%. (...)

(Anm: Antidepressant Treatment and Worsening White Matter on Serial Cranial Magnetic Resonance Imaging in the Elderly. Stroke 2008;39:857-862.)

(Anm: hvit substans; hvit substans, margkledde nervefibrer, utløpere fra nervecellene i hjerne og ryggmarg. Den hvite fargen skyldes myelin, et fettholdig stoff som danner margskjeder omkring nervefibrene. Kilde: Store norske leksikon.)

(Anm: white matter (hvit substans); Multiple Sclerosis (MS) is one of the most common disease which affects white matter (wikipedia.org).)

(Anm: Magnetic resonance imaging MRI findings in white matter disease of brain. J Pak Med Assoc. 2008 Feb;58(2):86-8.)

Selective serotonin reuptake inhibitor use associates with apathy among depressed elderly: a case-control study (Bruk av selektive serotoninreopptakshemmere er assosiert med apati blant deprimerte eldre: en case-control studie)
Annals of General Psychiatry 2007, 6:7
Background (Bakgrunn)
Det er det siste ti år rapportert at bruk av selektive serotoninreopptakshemmere (SSRI-er) kan være assosiert med forekomst av apati. (...) (It has been reported for over the past decade that the use of selective serotonin reuptake inhibitors (SSRI's) may associate with the emergence of apathy.)

Conclusion (Konklusjon)
Selv om depresjon ble bedre hos eldre pasienter som fikk antidepressiva, opptrådte apati oftere hos pasienter som ble behandlet med SSRI enn hos pasienter som ikke ble behandlet. Dysfunksjon i frontal lobe på grunn av serotonerge endringer er ansett som en av mulighetene. (...) (Even though depression was improved in elderly patients receiving antidepressants, apathy appeared to be greater in patients who were treated with SSRI than that found in patients who were not. Frontal lobe dysfunction due to alteration of serotonin is considered to be one of the possibilities.)

(Anm: apati (av gr. nektende a og 'affekt'), psykologisk og psykiatrisk begrep som betyr mangel på sjelelige følelser (affekter). Som regel ledsaget av interesseløshet. Sees særlig ved svære depressive og schizofrene tilstander.

(Anm: pannelappen; lobus frontalis, hjernens frontallapp; jf frontallappssyndromet EN frontal lobe.

frontallappssyndromet; eit særleg huglag (sinnelag) som kan koma etter skade i ein pannelapp i hjernen, t d etter lobotomi; pasienten får eit grunt kjensleliv, vert urimeleg overflatisk og lett til sinns, likesæl og godtruande; også kalla frontal psyke; jf Witzelsucht (ty.) EN frontal lobe syndrome. Kilde: Norsk medisinsk ordbok.)

Vanlige utfall etter ervervet hjerneskade
sunnaas.no 26.2.003
(...) Det er rapportert at noen pasienter blir passive og apatiske. Noen er det fordi de har blitt deprimerte, mens det for andre er et direkte resultat av skaden. Noen blir også urolige og kritikkløse. Ofte er slike endringer i oppførsel det de pårørende synes er vanskeligst å forholde seg til. (...)

THE PEOPLE'S PHARMACY
infoweb.newsbank.com 14.7.2007 (The Dallas Morning News)
Serotonin has become a household word, thanks to Prozac. Millions of people take this popular antidepressant or related drugs such as Zoloft and Paxil every day.

These medications are known scientificallyas SSRIs: selective serotonin reuptake inhibitors. They allow serotonin to accumulate between nerve endings. This brain chemical helps to regulate mood and appears to be important for sleep, learning, appetite, sexual behavior, pain, perception and movement.

But although serotonin is essential for good health, it has a darker side. Too much serotonin can cause bizarre behavior, and some people taking these medications might be at risk of life-threatening drug interactions.

Serotonin syndrome can cause a range of problems, from anxiety, agitation and muscle twitches to nausea, sweating, confusion, convulsions and even coma. (...)

"...forstyrret følesans og opplevelser av "elektriske støt" i hodet" (...) "...følelse av elektriske støt i hodet, andre blir svimmel og psykisk urolig"

Hva er antidepressivt nedtrappingssyndrom?
pasienthandboka.no/ 17.4.2007
Stans i behandlingen med antidepressiv medikasjon (antidepressiva) er noen ganger forbundet med utvikling av et såkalt "antidepressivt nedtrappingssyndrom" (syndrom betyr samling av mange symptomer). Symptomene kan være forkjølelsesliknende, søvnproblemer, kvalme, svimmelhet, forstyrret følesans og opplevelser av "elektriske støt" i hodet. Alle typer antidepressiva er rapportert å kunne gi slike reaksjoner, enten som følge av brå stans eller for rask nedtrapping av behandlingen. De mest brukte antidepressiver betegnes SSRI (Fluoxetin, Fontex, Citalopram, Cipramil, Paroxetin, Seroxat, Sertralin, Zoloft, Fevarin, Cipralex), trisykliske antidepressiver (Klomipramin, Anafranil, Surmontil, Sarotex, Noritren, Sinequan) og MAO-hemmere (Moklobemid, Aurorix). Atypiske antidepressiver er Mianserin, Tolvon, Mirtazapin, Efexor, Edronax, Cymbalta, Yentreve.
Kjennskap til antidepressivt nedtrappingssyndrom er viktig fordi selv om symptomene ofte er milde, kan tilstanden gi mye ubehag, fravær fra jobb, andre psykososiale problemer og unntaksvis kreve sykehusinnleggelse. (...)

SSRI mot depresjon
pasienthandboka.no 27.2.2008
(SSRI betyr selektiv, serotonin reopptaks inhibitor) (...)

Mange er redd for avhengighet ved bruk av nervemedisiner. Medikamentene som brukes ved depresjoner gir ingen ruseffekt eller umiddelbar lykkefølelse, og heller ikke avhengighet (derfor er tilnavnet lykkepiller misvisende). Derimot kan man oppleve ubehag når man slutter med medisinene. Mange beskriver en følelse av elektriske støt i hodet, andre blir svimmel og psykisk urolig. Dette kan være skremmende dersom man ikke vet om det. Denne bivirkningen kan man unngå eller betydelig redusere ved å trappe langsomt ned dosene når man slutter. (...)

Hvilke symptomer ser vi ved MS?

Hvilke symptomer ser vi ved MS?
MS.NO 4.12.2002
SYMPTOMER
MS omfatter inflammasjon i sentralnervesystemet som etterfølges av tap av de beskyttende myelin skjedene som omgir nervefibrene [demyelinisering]. Myelinet virker som isolasjonsmateriale som omgir og beskytter elektriske ledninger. Når myelinet tar skade vil ikke nerveimpulsene kunne overføres så hurtig og effektivt som de skal. Som et resultat av den inflammatoriske prosessen vil det oppstå skadde områder [lesjoner eller plaques] i hjerne og ryggmarg som i sin tur gir ulike nevrologiske symptomer.

Vanlige symptomer kan være synstap, nummenhet og vissenhet, kraftsvekkelse, ustø gange, dobbeltsyn, økt trøttbarhet, varmeintoleranse, delvise eller fullstendige lammelser og en fornemmelse av elektrisk støt langs ryggsøylen ved bøyning i nakken. Symptomene kan forsvinne etter et akutt attakk, men kan også bli værende. (...)

Brain-damaged people give insights into morality (Hjerneskadede mennesker gir innblikk i moral)
reuters.com 22.3.2007
WASHINGTON (Reuters) - Det er krigstid, og en lege hos fienden utfører smertefulle/dødelige eksperimenter på barn. (- It's wartime, and an enemy doctor is conducting painful and inevitably fatal experiments on children.)

Du har to barn som er 8 og 5 år. You can surrender one of them within 24 hours or the doctor will kill both. What is the right thing to do? (You have two kids, ages 8 and 5. You can surrender one of them within 24 hours or the doctor will kill both. What is the right thing to do?)

For de fleste mennesker er dette scenariet, som er hentet fra en novelle av William Styrons, "Sophie's Choice", nesten et umulig dilemma. Men for en gruppe mennesker med skade i en del av hjernens frontal lobe, som hjelper å styre følelser, er beslutningen mye klarere. De ville velge ut et barn som skulle dø. (For most people, this scenario based on one in William Styron's novel "Sophie's Choice" is almost an impossible dilemma. But for a group of people with damage in a part of the brain's frontal lobe that helps govern emotions, the decision was far more clear. They would choose one child for death.)

Scientists said on Wednesday a study involving these people has produced unique insights into the brain mechanics of moral decision making and showed that in some key situations emotions play a fundamental role in moral judgments.

The new findings highlighted the role of a region in the front part of the brain below the eyes called the ventromedial prefrontal cortex.

Earlier research had pegged this area -- one of the more recently evolved parts of the human brain -- as playing a role in generating social emotions. In fact, the people with damage in this region due to stroke or other causes experienced severely diminished empathy, compassion and sense of guilt.

The new findings published in the journal Nature seem to confirm its central role in guiding certain moral judgments like life-or-death scenarios. (...)

Another wartime scenario involved enemy troops searching for civilians to kill. The people in the study were asked about their willingness to kill their own infant whose crying was drawing the attention of enemy soldiers who would then kill the parent, the baby and people hiding with them.

Again, the people with this brain damage were far more willing to judge killing the baby as the right moral choice. (...)

Vanlige utfall etter ervervet hjerneskade
sunnaas.no 26.2.003
(...) Det er rapportert at noen pasienter blir passive og apatiske. Noen er det fordi de har blitt deprimerte, mens det for andre er et direkte resultat av skaden. Noen blir også urolige og kritikkløse. Ofte er slike endringer i oppførsel det de pårørende synes er vanskeligst å forholde seg til. (...)

THE PEOPLE'S PHARMACY
infoweb.newsbank.com 14.7.2007 (The Dallas Morning News)
Serotonin has become a household word, thanks to Prozac. Millions of people take this popular antidepressant or related drugs such as Zoloft and Paxil every day.

These medications are known scientificallyas SSRIs: selective serotonin reuptake inhibitors. They allow serotonin to accumulate between nerve endings. This brain chemical helps to regulate mood and appears to be important for sleep, learning, appetite, sexual behavior, pain, perception and movement.

But although serotonin is essential for good health, it has a darker side. Too much serotonin can cause bizarre behavior, and some people taking these medications might be at risk of life-threatening drug interactions.

Serotonin syndrome can cause a range of problems, from anxiety, agitation and muscle twitches to nausea, sweating, confusion, convulsions and even coma. (...)

Andre teorier

Protein avgjør hvor godt du takler motgang
vg.no 25.10.2007
(VG Nett) Et protein i hjernen styrer hvor godt du takler motgang, viser ny forskning. (...)

Nå hevder forskere i en ny studie at det er mengden av proteinet Brain-derived neutrophic factor (BDNF) som styrer hvor godt vi takler påkjenninger, og nivået er merkbart lavere hos personer som ikke takler det så godt.

Tidligere studier har vist at deprimerte har et lavere nivå av hjerneproteinet sammenliknet med ikke-deprimerte. (...)

- Tren og spis sunt
- Både aktivitet og diett kan ha god effekt på produksjon av BDNF og andre funksjoner i hjernen. Det å være i fysisk aktivitet har vist seg å øke BDNF, og stimulering av miljø har også god effekt. Stress over lengre tid kan være med på å redusere mengde BDNF i enkelte deler av hjernen, sier hun, og gir følgende råd:

- Tren, spis sunt og ikke utsett deg for stress over lengre tid. (...)

(Anm: Fysisk trening (aktivitet / løping / jogging).)

Protein kan ligga bakom depression
dn.se 9.1.2006
Den svenska neurofarmakologen Per Svenningsson har funnit en koppling mellan två funktioner i hjärnan som kan vara ett forskningsgenombrott i förståelsen av sjukdomen depression.

Depression är en mycket vanlig sjukdom som drabbar varannan kvinna och var fjärde man någon gång under en livstid.

Läkemedelsbehandlingen av depression enbart i Sverige kostar över en miljard kronor varje år. Men forskarna vet fortfarande väldigt lite om hur utvecklingen av sjukdomen egentligen går till inne i kroppen.

Nu kan den svenska neurofarmakologen docent Per Svenningsson vid Karolinska institutet i Stockholm vara depressionens mekanism på spåren. Hans forskning har just publicerats i vetenskapliga tidskriften Science. (...)

Det finns fortfarande mycket forskning kvar att göra innan depressionens gåta är löst. Och det är också troligt att det är flera proteiner och gener som är involverade vid utvecklingen av depression. Det kommer därför att ta tid innan någon ny behandling finns att tillgå.

- Men jag tror att min strategi att specifikt studera mekanismerna bakom sjukdomen kommer att leda till att vi i framtiden kommer att kunna behandla depression på ett bättre sätt, säger Per Svenningsson. (...)

Implant eases depression with zaps of happiness
seattletimes.nwsource.com 8.1.2006
Implant eases depression with zaps of happiness

For two decades, Meir Samel was severely depressed. Ultimately, he said, his prolonged sadness and feelings of worthlessness cost him his job and his marriage.

"It just messed up my whole life. I really couldn't function," said the 66-year-old biochemist, who took an early retirement at age 49.

Today, Samel feels better than he has in years, thanks to a pacemakerlike device implanted in his chest three months ago.

The implant was approved by the government in July for people with treatment-resistant depression — that is, the kind that does not respond to multiple medications or other psychiatric therapies.

The implant works by delivering mild, intermittent electrical pulses to the left vagus nerve in the neck, one of a dozen cranial nerves that serve as the body's "information highway." The nerve then activates areas of the brain believed to regulate mood. (...)

Genes may indicate likelihood of depression
netdoctor.co.uk 6.1.2006
A gene which regulates a vital brain chemical may indicate whether or not an individual is likely to suffer from depression, US scientists have said.

A team from the Rockefeller University said the p11 gene, which regulates the levels of the brain chemical serotonin, could also be used to develop treatments for mental disorders such as depression.

The team of researchers, led by Professor Paul Greengard, found decreased levels of p11 in the brain were associated with the development of depression.

Professor Greengard said: "We have shown that a gene called p11 is involved in the multiple complex changes that underlie depression. (...)

Antidepressiva, fettceller, benskjørhet, hjertesykdommer og immunsystem

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. (...)

Sick and down (Syk og nedfor)
sciencenews.org 4.7.2008
To fight off an infection or illness, the body shifts into a slow-down mode that mirrors some symptoms of depression. In fact, scientists now think the immune response itself may even cause the mood disorder.

From Sick to DownImmune cells secrete cytokines (shown as red dots in this simplified drawing, click on image to see larger version) that trigger inflammatory responses. But when cytokine levels in the brain stay high fo too long, people susceptible to mood disorders may develop depression. Cytokines released in the body may enter the brain directly, by passing through leaky areas in the blood-brain barrier, or indirectly by initiating a chain reaction of "middlemen" that lead to brain cells called microglia releasing cytokines. Cytokines may alter mood by changing brain processes and levels of brain chemicals such as serotonin and dopamine. Synthetic version of interferon-alpha and interferon-beta, used to treat cancers, hepatitis C and multiple sclerosis, may engage the same pathway. (...)

Psykiske lidelser og hjertesykdom
Tidsskr Nor Lægeforen 2007; 127: 2126-7
(...) Det er i flere studier vist at også antidepressive medisiner fører til signifikant økning av lipidnivået i blodet. Derfor bør pasienter som behandles med antipsykotiske, antidepressive og stemningsleiestabiliserende midler få blodlipidnivået kontrollert regelmessig. (...)

Overraskende om skjelettet
forskning.no 13.8.2007
(...) - Regulerer stoffskiftet
- Jeg var overrasket over hvor omfattende funnene var. Det ser ut til at skjelettet er en reostat som regulerer stoffskiftet, sier Gerard Karsenty til Nature. (...)

Karsenty er entusiastisk, men nøye med å påpeke at man må forske mer for å finne ut akkurat hvor mye disse hormonene har å si for kroppen. (...)

Newtonsk premiss
Bakgrunnen for oppdagelsen er at Karsenys forskning tidligere hadde vist at fettceller påvirket stoffskiftet i benbygningen. (...)

Lipidmetabolismen reguleres av immunsystemet
Tidsskr Nor Lægeforen 2007; 127 (31.5.2007)
Hyperlipidemi er ofte forbundet med inflammasjon. Ny forskning på mus har vist at de proinflammatoriske cytokinene lymfotoksin og LIGHT (homolog til lymfotoksin), hovedsakelig produsert i T-lymfocytter, regulerer nøkkelenzymer i lipidmetabolismen (Science 2007; 316: 285 - 8). (...)

Antidepressive medikamenter påvirker kroppens fettproduksjon
NY DOKTORGRAD
uib.no (23.9.2006)
Cand. med. Maria Barøy Ræder disputerer fredag 29. september for PhD graden ved Universitet i Bergen med avhandlingen:

”Lipid-related effects of antidepressant and antipsychotic drugs: A molecular and epidemiological study”

Medikamenter som brukes i behandlingen av depresjon er i hyppig og økende bruk i Norge. Denne økningen har særlig kommet etter at en ny medikament-gruppe mot depresjon ble introdusert, de såkalte SSRI-medikamentene (”lykkepiller”). Avhandlingen handler om medisiner brukt ved depresjon og hvordan disse påvirker fettproduksjonen i kroppen, både på et klinisk- og på et molekylært plan.

På det kliniske planet benyttet Ræder data fra Helseundersøkelsen i Hordaland (HUSK) og viste at pasienter som brukte SSRI-medikamenter oftere hadde økt risko for hjerte-karsykdom. Særlig viktig var det at personer som brukte antidepressive legemidler hadde høyere forkomst av de disponerende risikofaktorene overvekt og forhøyete kolesterolverdier. Tidligere har man vist at antipsykotiske medisiner disponerer for overvekt. (...)

På det molekylære planet tok Ræder i bruk cellestudier og moderne genteknologiske metoder for å vise at de store gruppene av psykiatriske medisiner (antipsykotika og antidepressiva, inkludert SSRI-medikamenter) virker på fettomsetningen i kroppen gjennom en transkripsjonsfaktor kalt SREBP (steroid reseptor-element bindende protein). SREBP er meget viktig for å regulere produksjon både av kolesterol og av ulike fett-stoffer i kroppens celler. Kolesterol og andre fett-stoffer er viktig for at nevroner skal utvikle seg og fungere normalt, men har også en rolle i utviklingen av hjerte- og karsykdom. (...)

Nurse 'shocked to death' by alarm
bbc.co.uk 28.4.2006
Lisa Browne died suddenly in her bed in 1998
A nurse died from heart failure brought on by the shock of her alarm clock going off, an inquest has heard.

Lisa Browne, who was originally from Stoke-on-Trent, died suddenly in her bed in 1998. She was 27. (...)

Heart specialists in London, who investigated the case last year, confirmed the paediatric nurse was suffering from Long QT Syndrome. (…)

The attorney general ordered a fresh inquest and the original verdict, given in August 1998, to be quashed. (...)

She complained on a number of occasions to her GP, who prescribed her a low dose of an antidepressant which she took for a few months from October 1996.

The antidepressant should not be taken by anyone suffering from Long QT syndrome, the inquest heard. (…)

SSRI-preparat kan ge förlängd QTc-tid
lakartidningen.se 4.4.2006
Selektiva serotoninåterupptagshämmare (SSRI) har visats kunna ge hjärtbiverkningar, främst QTc-förlängning, som disponerar för ventrikulära arytmier av typ ”torsade de pointes”. SSRI kan därför inte längre betraktas som riskfria från hjärtsynpunkt. Vid behandling med dessa medel bör patientens hjärtstus, EKG och eventuella riskfaktorer uppmärksammas. Nyligen antagna internationella riktlinjer kan öka den kardiovaskulära säkerheten vid läkemedelsbehandling.

Läkemedelsutlöst arytmi svårfångad biverkan

Citalopram inte riskfritt från hjärtsynpunkt (...)

Antidepressants Boost Heart Patients' Death Risk (Antidepressiva øker hjertepasienters dødsrisiko)
healthfinder.gov 5.3.2006
Overraskende resultat, trenger ytterligere granskning, ifølge eksperter. (Finding surprising, needs further study, experts say.)

Menn og kvinner med koronararteriesykdom som tar antidepressiva synes å ha en høyere dødsrisiko, antyder overraskende ny forskning. (Men and women with coronary artery disease who take antidepressants appear to be at a higher risk of dying, surprising new research suggests.)

Der er ingen enkel forklaring på resultatene, som motsier tidligere studier. (There was no ready explanation for the finding, which contradicts previous studies.)

"Dette var et uventet funn," sa medforfatter av studien, James Blumenthal, professor i medisinsk psykologi ved Duke University Medical Center. "Der er ingen åpenbar forklaring." ("This was an unexpected finding," said study co-author James Blumenthal, a professor of medical psychology at Duke University Medical Center. "There is no obvious explanation.")

Men, han la til, "det er uriktig å konkludere at antidepressiva forårsaket pasientenes død." (But, he added, "it is improper to conclude that antidepressants caused the patients to die.")

"Det strider imot hva vi hadde håpet>," tilla dr. Nieca Goldberg, sjef for hjertebehandling av kvinner ved Lenox Hill Hospital i New York City og talsmann for American Heart Association. "Men vi kan ikke bevise det på den ene eller annen måte." ("It contradicts what we were hoping," added Dr. Nieca Goldberg, chief of women's cardiac care at Lenox Hill Hospital in New York City and a spokeswoman for the American Heart Association. "But we can't prove it one way or the other.")

Forskningen, presentert lørdag på møte til American Psychosomatic Society i Denver, viste at, selv etter justering for ulike faktorer, fant forskerne at hjertepasienter som tok antidepressiva hadde 55 prosent høyere dødsrisiko enn de som ikke tok antidepressiva. Der var ingen statistisk signifikant forskjell mellom de som tok selektive serotoninreopptakshemmere (SSRI-er) og de som tok andre typer av antidepressiva. (...) (The research, presented Saturday at the American Psychosomatic Society meeting in Denver, showed that, even after adjusting for a variety of factors, the researchers found heart patients taking antidepressants had a 55 percent higher risk of dying than those not taking antidepressants. There was no statistical significant difference between those taking selective serotonin reuptake inhibitors (SSRIs) and those taking other types of antidepressants.)

Effects of paroxetine on cardiovascular response to mental stress in subjects with a history of coronary artery disease and no psychiatric diagnoses. (Effekter av paroxetine på kardiovaskulær respons til mentalt stress hos personer med en historie av koronararteriesykdom og ingen psykiatrisk diagnose.)
Psychopharmacology (Berl) 2005;;182(3):321-6.)
(...) RESULTATER: Mens på paroxetine, var systolisk blodtrykk og diastolisk blodtrykk 10-15 % lavere (p < 0.005) i løpet av stressoren, i forhold til målinger oppnådd på placebo. Puls og plasma norepineprin-konsentrasjoner i løpet av stress tenderte å være lavere i løpet av paroxetine behandling men nådde ikke statistisk signifikans. (...) (RESULTS: While on paroxetine, systolic blood pressure and diastolic blood pressure were 10-15% lower (p < 0.005) during the stressor, relative to measures obtained while on placebo. Pulse and plasma norepinephrine concentrations during stress trended lower during paroxetine treatment but did not reach statistical significance.)

Antidepressiver øger risiko for hjertedød
dagensmedicin.dk 10.3.2006
Hjertepatienter, der tager antidepressiv medicin, har tilsyneladende en højere risiko for at dø. Det viser de foreløbige resultater af en undersøgelse, som i sidste uge blev fremlagt på en konference i USA.

Det er forskere fra det amerikanske Duke University Medical Center, der har fremlagt de overraskende resultater fra en undersøgelse af hjerte-kar-patienter. Undersøgelsen viste, at personer, der havde fået udført en koronararteriografi (KAG) og brugte antidepressive lægemidler, havde en signifikant forhøjet risiko for at dø, sammenlignet med patienter, der havde fået den samme undersøgelse, men ikke brugte disse lægemidler. Forskellen vedblev, efter at data var renset for forskelle i alder, køn, hjertets pumpeevne, rygevaner, andre sygdomme og uddannelse. (...)

Forskare hittade samband mellan antidepressiva och dödlighet
dagensmedicin.se 5.3.2006
Personer som har hjärt-kärlsjukdom och äter antidepressiva läkemedel verkar löpa en högre risk att dö, enligt preliminära forskningsresultat som presenterades i går.

Det är forskare vid Duke University Medical Center i USA som vid en konferens i går, lördagen den 4 mars, presenterade förvånande resultat från en studie av hjärt-kärlsjuka patienter. Det visade sig att personer som genomgått kärlröntgen och använde antidepressiva medel löpte en signifikant ökad risk att dö, jämfört med patienter som också genomgått kärlröntgen, men inte tog sådana läkemedel.

Skillnaden kvarstod när forskarna rensade för bland annat ålder, kön, hjärtats pumpningsförmåga, rökvanor, andra sjukdomar och utbildning. Det verkade också finnas en skillnad mellan så kallade SSRI-preparat och andra antidepressiva - SSRI-preparaten ledde till ökad dödlighet - men den var inte signifikant.

I den prospektiva studien analyserade forskarna data från 921 patienter som tagits in på sjukhus för kärlröntgen. Knappt en femtedel av dessa personer tog antidepressiva läkemedel.

Patienterna fick svara på ett test som användes för att avgöra om de led av depression eller inte. Sedan följdes patienterna i genomsnitt i tre år. Under denna tid avled 21,4 procent av de personer som tog antidepressiva medel, jämfört med 12,5 procent i gruppen som inte behandlades med sådana preparat.

Sedan andra faktorer rensats bort, hade gruppen som fick antidepressiva en 55 procent högre risk för att dö.

Forskarna vid Duke University förbereder nu en randomiserad studie för att undersöka vilken påverkan motion och SSRI-preparat kan ha på olika markörer för hjärt-kärlsjukdom. (...)

(Anm: Anti-Depressant, Heart Risk Association Needs Further Study.
dukemednews.org 4.2.2006.)

Cardiovascular Side Effects of New Antidepressants and Antipsychotics: New Drugs, old Concerns?
Current Pharmaceutical Design 2004;10(20)
The cardiovascular toxicity of older generation of tricyclic antidepressants (e.g. imipramine, desipramine, amitriptyline, clomipramine) and neuroleptics (e.g. haloperidol, droperidol, thioridazine, pimozide) is well established. These drugs inhibit cardiovascular Na+, Ca2+ and K+ channels often leading to life-threatening arrhythmia.

To overcome the toxicity of old generation of antidepressants and antipsychotics, selective serotonin reuptake inhibitor antidepressants (SSRIs: fluoxetine, fluvoxamine, paroxetine, sertraline, citalopram, venlafaxin) and several new antipsychotics (e.g. clozapine, olanzapine, risperidone, sertindole, aripiprazole, ziprasidone, quetiapine) were introduced during the past decade. Although these new compounds are not more effective in treating psychiatric disorders than older medications, they gained incredible popularity since they have been reported to have fewer and more benign side effect profile (including cardiovascular) than predecessors. (...)

SSRIer forårsaker blødninger

Recent findings from University of Southern Denmark highlight research in selective serotonin reuptake inhibitor
behavioralhealthcentral.com 5.3.2010
Investigators publish new data in the report 'An association between selective serotonin reuptake inhibitor use and serious upper gastrointestinal bleeding.' "In vitro studies have shown that selective serotonin reuptake inhibitors (SSRIs) inhibit platelet aggregation. It is controversial whether use of SSRIs is a cause of clinically important bleeding; results from observational studies have been equivocal," researchers in Denmark report (see also Selective Serotonin Reuptake Inhibitor). "A population-based case-control study was conducted in Denmark. The 3652 cases all had a first discharge diagnosis of serious upper gastrointestinal bleeding (UGB) from 1995 to 2006. Controls (n=36,502), matched for age and sex, were selected by risk-set sampling. Data on drug exposure and medical history were retrieved from a prescription database and the county's patient register. Confounders were controlled for by conditional logistic regression and the case-crossover design. The adjusted odds ratio (OR) of UGB among current, recent, and past users of SSRIs was 1.67 (95% confidence interval [CI], 1.46-1.92), 1.88 (95% CI, 1.42-2.5), and 1.22 (95% CI, 1.07-1.39). The adjusted OR for concurrent use of SSRI and nonsteroidal anti-inflammatory drugs (NSAIDs) was 8.0 (95% CI, 4.8-13). The adjusted OR for the concurrent use of NSAID, aspirin, and SSRI was 28 (95% CI, 7.6-103). Of the UGB cases, 377 were current users of SSRI; the adjusted OR for UGB in the case crossover analysis was 2.8 (95% CI, 2.2-3.6). The adjusted OR among users of proton pump inhibitors was 0.96 (95% CI, 0.50-1.82). Use of SSRI was associated with UGB, consistent with its antiplatelet effects," wrote M. Dall and colleagues, University of Southern Denmark.

The researchers concluded: "SSRIs should be prescribed with caution for patients at high risk for UGB." (...)

(Anm: An Association Between Selective Serotonin Reuptake Inhibitor Use and Serious Upper Gastrointestinal Bleeding. Clinical Gastroenterology and Hepatology, 2009;7(12):1314-21) (December).)

Use of selective serotonin reuptake inhibitors and risk of re-operation due to post-surgical bleeding in breast cancer patients: a Danish population-based cohort study (Bruk av selektive serotoninreopptakshemmere og risiko ved reoperasjon grunnet blødning etter operasjon hos brystkreftpasienter: en dansk befolkningsbasert kohortstudie)
BMC Surgery 2010, 10:3doi:10.1186/1471-2482-10-3 (24.1.2010)
Background
Selective serotonin reuptake inhibitors (SSRI) decrease platelet-function, which suggests that SSRI use may increase the risk of post-surgical bleeding. Few studies have investigated this potential association. (...)

Results
389 of 14,464 women (2.7%) were re-operated. 1592 (11%) had a history of SSRI use. Risk of re-operation was 2.6% among never users, 7.0% among current SSRI users, and 2.7% among former users. Current users thus had an increased risk of re-operation due to post-operative bleeding (adjusted relative risk=2.3; 95% confidence interval (CI)=1.4, 3.9) compared with never users. There was no increased risk of re-operation associated with former use of SSRI (RR=0.93, 95% CI= 0.66, 1.3). (...)

Anti-depressants And Painkillers Combined Linked To Gastrointestinal Bleeding
sciencedaily.com 9.10.2007
Science Daily — New research shows that selective serotonin reuptake inhibitors (SSRIs), a group of drugs commonly used to treat depression, may double the risk of gastrointestinal bleeding, according to researchers from Wake Forest University School of Medicine and colleagues. When the drugs are taken with aspirin and other similar pain medications, the risk is more than 600 percent higher. (...)

SSRIs and gastrointestinal bleeding (SSRI og gastrointestinal bløding)
BMJ 2005;331:529-530 (10 September)
Der er teoretiske grunner til å tro at selektive serotoninreopptakshemmere (SSRIs), mye brukt til å behandle depresjon, kan øke risikoen for gastrointestinal bløding. (...) (There are theoretical reasons for believing that selective serotonin reuptake inhibitors (SSRIs), widely used to treat depression, might increase the risk of gastrointestinal bleeding.)

Serotonin er frigjort fra blodplater (trombocytter) som respons på vaskulær skade og aktiverer vasokonstriksjon (sammentrekning av blodårene) og en forandring i formen på blodplatene som fører til aggregasjon (sammenklumping av blodplater til tromber (blodpropper)).¹ Blodplater kan ikke selv syntetisere serotonin. SSRI-er hemmer serotonintransporten, som er ansvarlig for opptaket av serotonin i blodplatene. Det kunne således forutsis at SSRi-er ville tømme blodplatene for serotonin, som fører til redusert evne å danne klumper med påfølgende økning i risikoen for blødning. (Serotonin is released from platelets in response to vascular injury and promotes vasoconstriction and a change in the shape of the platelets that leads to aggregation.¹ Platelets cannot themselves synthesise serotonin. SSRIs inhibit the serotonin transporter, which is responsible for the uptake of serotonin into platelets. It could thus be predicted that SSRIs would deplete platelet serotonin, leading to a reduced ability to form clots and a subsequent increase in the risk of bleeding.)

Vi har gjennomgått de publiserte databasestudier på sammenhengen mellom bruk av SSRI og gastrointestinal blødning. Fire av disse studier sammenliknet risikoen for en blødning i øvre delen av mage-tarm-kanalen hos de som er forskrevet SSRi-er med de som ikke er det. Oddsratioer for en blødning hos en SSRI-behandlet pasient varierte fra 1,38 til 3,6: 3,0 (95% konfidensintervall 2,1 til 4,4),² 3,6 (2,7 til 4,7),³ 2,1 (0,6 til 8,3),⁴ og 1,38 (0,82 to 2,34).⁵ Denne omtrent tredoble økning i risiko kan også gjede for andre typer blødninger. Movig et al rapporterte at pasienter som tar SSRI-er var 3,71 (1,35 til 10,18) ganger mer sannsynlig å kreve blodtransfusjon under ortopedisk kirurgi enn pasienter som ikke tar dem.⁶ Meijer el al rapporterte at kvinner som tar SSRIs med en høy affinitet til serotonin transport var 3,0 (0,8 til 4,9) ganger mer sannsynlig å erfare uvanlig livmorblødning enn kvinner som tok antidepressiva med lav affinitet.⁴ (We have reviewed the published database studies on the relation between SSRI use and gastrointestinal bleeding. Four of these studies compared the risk of an upper gastrointestinal bleed in those prescribed SSRIs with those who were not. The odds ratios of a bleed in an SSRI-treated patient ranged from 1.38 to 3.6: 3.0 (95% confidence interval 2.1 to 4.4),² 3.6 (2.7 to 4.7),³ 2.1 (0.6 to 8.3),⁴ and 1.38 (0.82 to 2.34).⁵ This roughly threefold increase in risk may also hold for other types of bleeding. Movig et al reported that patients taking SSRIs were 3.71 (1.35 to 10.18) times more likely to require a blood transfusion during orthopaedic surgery than patients not taking them.⁶ Meijer el al reported that women taking SSRIs with a high affinity for the serotonin transporter were 3.0 (0.8 to 4.9) times more likely to experience abnormal uterine bleeding than women who took antidepressants with low affinity for this transporter.⁴)

En forbindelse mellom risikoen for blødning og økende affintitet for serotonin transportering har vært bemerket i flere studier,^{2 4 7} selv om konfidensintervaller for de siterte oddsratioer overlapper betraktelig. (...) (An association between the risk of bleeding and increasing affinity for the serotonin transporter has been noted in several studies,^{2 4 7} although the confidence intervals around the quoted odds ratios overlap considerably.)

Rapid Responses
Bortsett fra gastrointestinal blødning, økte SSRI-er også risikoen for livmorsblødning, hjerneblødning, unormal blødning i ledd, neseblod, og blødning i urinblære. Dette kan være et resultat av følgende mekanismer. Blodplatefaktor 4 og beta-tromboglobulin er to trombogeniske proteiner frigitt i blodet når blodplater er aktivert. Serotonin potensierer blodplateaktivering. SSRI-er reduserer serotoninopptak fra blod til blodplater. Siden blodplater ikke fremstiller serotonin, er SSRi-er forbundet med økninger i blødningsepisoder. (...) (Apart from gastrointestinal bleeding,SSRIs also increase the risk of uterine bleeding, brain hemorrhages, abnormal bleeding in joints, nose bleeds, and bleeding within the bladder. This may result due to following mechanisms. Platelet factor-4 and beta-thromboglobulin are two thrombogenic proteins released into the blood when platelets are activated. Serotonin potentiates platelet activation. SSRIs decrease serotonin uptake from blood to platelets. Since platelets do not synthesize serotonin, SSRIs are associated with increases in bleeding episodes.)

(Anm: gastrointestinal bleeding; gastrointestinal bløding; «g.i.bløding», bløding frå øsofagus, magesekk eller tarm; kan gi synleg blod i avføringa, gjerne som svart farge (melena) eller positiv kjemisk prøve for blod utan synleg endring (okkult bløding); stundom brukast uttrykka øvre- eller nedre g.i. bløding; jf tarmbløding, okkult bløding. EN gastrointestinal bleeding. BM gastrointestinal blødning. Kilde: Norsk medisinsk ordbok.)

(Anm: platelet; trombocytt; thrombocytt, blodplate; små plateliknande kjernelause lekamar i blodet som er viktige for blodlevringa; dei kan hefta seg til kvarandre, til årevegger eller sårvev og desse samanklumpingane kan dekka skadar i endotel og tena som pluggar som stansar småblødingar, og dei kan frisetja koagulasjonsfaktorar; dei vert danna ved avsnøringar frå megakaryocyttane i beinmargen; dei inneheld alfa-granula som lagrar fibrinogen, PDGF, TGFb, faktor V, Willebrandfaktor m v, og delta-granula (dense granules)som inneheld serotonin og ADP og har på overflata reseptorar (P2Y) for ADP, sjå også trombospondin, glykoproteinkompleks og PDGF; trombocyttane kan vera med i framveksten av arteriosklerose og ved blodproppsjukdommar; jf trombopoetin, tromboksan, viskøs metamorfose. EN platelet; thrombocyte. ET [gr thrombos blodlevre + kytos holrom, celle]. Kilde: Norsk medisinsk ordbok.)

SSRI-er og mulig lungeemboli (PE)

Thoracic Ultrasound for Diagnosing Pulmonary Embolism: A Prospective Multicenter Study of 352 Patients. (Ultralyd av bryst for diagnostisering av lungeemboli: En prosoektiv multisenterstudie av 352 pasienter.)
Chest 2005;128(3):1531-1538 (September 2005)
BAKGRUNN: Lungeemboli (PE) fortsetter å være en stor diagnostisk utfordring, som vist ved det faktum at mange pasienter dør udiagnostisert og/eller ubehandlet. Målet for denne multisenterstudie var å bestemme nøyaktigheten av ultralyd av thorax (TUS) ved diagnosen av PE (TUSPE). (...) (BACKGROUND: Pulmonary embolism (PE) continues to be a major challenge in terms of diagnosis, as evidenced by the fact that many patients die undiagnosed and/or untreated. The aim of this multicenter study was to determine the accuracy of thorax ultrasound (TUS) in the diagnosis of PE (TUSPE).)

Resultater: PE ble diagnostisert hos 194 pasienter. Ved TUS, hadde 144 pasienter samlet 333 subpleurale lesjoner (middelverdi, 2,3 lesjoner per pasient) gjennomsnittlig 15,5 x 12,4 mm i størrelse. I tillegg ble en snever pleural effusjon funnet hos 49 % av paientene. TUS ga følgende resultater ved bruk av de strenge kriterier 1 og 2: PE sann-positiv, n = 144; PE falsk positiv, n = 8; PE sann-negativ, n = 150; og PE falsk-negativ, n = 50. Sensitiviteten var 74%, spesifisitet var 95 %, positiv prediktiv verdi var 95 %, negativ prediktiv verdi var 75 %, og nøyaktighet var 84 %, med en prevalens på 55 %. Sensitiviteten hos pasienter med criterion 1 var 43 % og en spesifisitet på 99 %. Fortolkning: TUS er en ikke-invasiv metode for å diagnostisere perifer PE. I fraværet av CTPA, er TUS et egnet verktøy til å påvise PE ved sykesengen eller akuttsituasjoner. (...) (Findings: PE was diagnosed in 194 patients. On TUS, 144 patients had a total of 333 subpleural lesions (mean, 2.3 lesions per patient) averaging 15.5 x 12.4 mm in size. Additionally, a narrow pleural effusion was found in 49% of the patients. TUS yielded the following results under application of the strict criteria 1 and 2: PE true-positive, n = 144; PE false-positive, n = 8; PE true-negative, n = 150; and PE false-negative, n = 50. The sensitivity was 74%, specificity was 95%, positive predictive value was 95%, negative predictive was value 75%, and accuracy was 84%, at a prevalence of 55%. The sensitivity in patients with criterion 1 was 43% and a specificity of 99%. Interpretation: TUS is a noninvasive method to diagnose peripheral PE. In the absence of CTPA, TUS is a suitable tool to demonstrate a PE at the bedside and in the emergency setting.)

(Anm: pulmonary embolism (PE); lungeemboli; embolia arteriae pulmonalis; blodpropp til lungene, d e til lungepulsåra, kan ha opphav i årebetennelse i bein, armar eller i vena cava, har lett for å koma i dagane etter ein operasjon; små lungeemboliar treng ikkje gi plager, store emboliar kan gi brått innsettande brystsmerter, hoste, av og til med blodig oppspytt, tung pust, gjerne takykardi m v; kan føra til brå død; i tillegg til ein trombosetendens (s d) kan røyking og høgt blodtrykk disponera for lungeemboli; jf pulmonal angiografi, Q-skanning, V-skanning. EN pulmonary embolism. Kilde: Norsk medisinsk ordbok.)

(Anm: subpleural; subpleuralis; som er under eller like innanfor brysthinna (pleura). EN subpleural. Kilde: Norsk medisinsk ordbok.)

Fatal venous thromboembolism associated with antipsychotic therapy (Dødelig venøs tromboembolisme assosiert med antipsykotisk terapi)
Ann Pharmacother 2004;38(9):1435-8 (September 2004)
(...) CASE-SAMMENDRAG: En 47 år gammel kvinne behandlet med clozapine og paroxetine ble innlagt på sykehus med dyspné og hevelse i leggene. Pasienten ble diagnostisert med PE og ble behandlet intravenøst med heparin. Pasienten utviklet på dag 7 på sykehuset plutselig akutt åndedrettssvikt og døde. Obduksjon bekreftet eksistensen av massiv PE. (CASE SUMMARY: A 47-year-old woman treated with clozapine and paroxetine was admitted to the hospital with dyspnea and swelling of the leg. The patient was diagnosed as having PE and was treated with intravenous heparin. On hospital day 7, sudden acute respiratory failure developed and the patient died. Postmortem examination confirmed the existence of massive PE.)

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

(Anm: pulmonary embolism (PE); lungeemboli, se forklaring ovenfor.)

DISKUSJON: Kvinnen hadde ingen andre identifiserbare risikofaktorer enn inntak av en kombinasjon av clozapine og paroxetine, med en påvist forhøyet konsentrasjon av clozapine i blod. Bruk av Naranjo-sannsynlighetsskala viste en mulig sannsynlighet for at den uheldige reaksjonen var legemiddelrelatert. (DISCUSSION: The woman had no identifiable risk factors other than receiving a combination of clozapine and paroxetine, with a demonstrated elevated clozapine blood concentration. Use of the Naranjo probability scale revealed a probable likelihood that the adverse reaction was drug related.)

KONKLUSJONER: Forbindelsen mellom antipsykotiske legemidler og venøs blodproppsjukdom er tidligere blitt beskrevet, men er fremdeles et sjeldent funn. Dette tilfellet understreker viktigheten av overvåking og mulig avbrytelse av behandling når venøs trombose er mistenkt. Det bør grundig overvåkes, spesielt hos pasienter med risikofaktorer for trombose. Til slutt kan antidepressiva-antipsykotika kombinasjoner øke risikoen for sjeldne uheldige effekter, slik som venøs blodproppsjukdom, selv med fravær av andre risikofaktorer. (...) (CONCLUSIONS: The association of antipsychotic drugs and venous thromboembolism has been previously described, but is still a rare finding. This case highlights the importance of monitoring and possibly discontinuing treatment when venous thrombosis is suspected. There should be careful monitoring, especially in patients with risk factors for thrombosis. Finally, antidepressant-antipsychotic drug combinations can increase the risk of rare adverse effects, such as venous thromboembolism, even in the absence of other risk factors.)

(Anm: dyspné; tung pust, andpust, kort pust, vanskeleg andedrett, pustevanskar; kjensla av dyspné skal vera utløyst av impulsar frå pustemusklane og senene deira, impulsar frå hjerneborken og visstnok også frå kjemoreseptorar ved blodgassendringar. EN dyspnea ET [gr dyspnoia]. Kilde: Norsk medisinsk ordbok.)

(Anm: tromboembolisme; blodproppsjukdom, d e tiltetting av blodårer av blodlevrer, blodplateklumpar eller andre faste emne som vert førde med blodstraumen; jf trombose, emboli. EN thromboembolism. Kilde: Norsk medisinsk ordbok.)

SSRI-indusert benskjørhet (osteoporose) og hjertesykdom

Hazards: Antidepressant Linked to Fractures in Older People
nytimes.com 30.1.2007
Daily use of a common class of antidepressant may double the risk of fracture in people older than 50, a Canadian study reports. (...)

Depression and Inflammation may go Hand-in-Hand
ivanhoe.com 1.9.2006-- People who are depressed are more likely to have exaggerated inflammatory responses to stressful situations, according to the results of a study released this week. Now, researchers want to know if that inflammation is behind the link between depression and heart disease ... or if it's the actual cause of depression. (...)

Ny mekanism funnen bakom inflammation vid åderförkalkning
dagensmedicin.se 9.5.2006
En forskargrupp vid Karolinska institutet i Solna har upptäckt mekanismer kring den inflammatoriska processen vid bland annat åderförkalkning, något som kan bana väg för nya läkemedel.

Forskarna från Solna har upptäckt att ämnen som bildas vid en inflammatorisk process, som till exempel cytokiner, bidrar till att förstärka inflammationen i blodkärlen ytterligare på ett sätt som tidigare inte beskrivits.

De inflammatoriska substanserna får celler i blodkärlens väggar att uttrycka receptorer för leukotrien B4, LTB4, ett ämne som i sig är starkt inflammatoriskt. När cellerna sedan reagerar på LTB4 förstärks inflammationen ytterligare.

Det har tidigare inte varit känt att cellerna i blodkärlens väggar kan reagera på LTB4. Upptäckten ökar förståelsen för den inflammatoriska processen, och bidrar till utvecklingen av läkemedel som på sikt kan få användning för flera sjukdomar med kroniska inflammationer, som till exempel ledgångsreumatism, astma och åderförkalkning, enligt ett pressmeddelande från Karolinska institutet.

Forskarna har publicerat sin studie i senaste numret av den vetenskapliga tidskriften Pnas. (...)

(Anm: Cannabis smokers 'at risk of brittle bone disease' (Cannabis røkere “løper risiko for beinskjørhet”.) Independent 23.5.2005.)

Lykkepiller kan øke risiko for beinskjørhet
forskning.no 28.11.2005
400 000 nordmenn bruker i dag såkalte lykkepiller. Pillene kan gi varige skader på skjelettet. (...)

- Lykkepillen hemmer nemlig aktiviteten til de beinbyggende cellene. Samtidig øker den produksjonen av signalstoffer som stimulerer til økt nedbryting av beinmassen.

Det sier Björn I. Gustafsson, stipendiat ved NTNU og overlege ved St. Olavs Hospital. Han har påvist denne medisinske sammenhengen ved cellestudier, som en del av sitt doktorgradsarbeid.

Endrer kjemi, bryter ned bein
Ved bruk av lykkepiller (også kalt SSRI-medikamenter) økes mengden serotonin lokalt i hjernen. Serotonin er et viktig signalstoff i hjernen. Mesteparten av kroppens serotonin produseres av bestemte celler i kroppens mage- og tarmsystem.

Økt mengde av serotonin i hjernen har positiv effekt på depresjoner og andre psykiske lidelser. Men lykkepiller påvirker også nivået og funksjon av serotonin i resten av kroppen. (...)

Fin balanse
Ved normal beindannelse i en menneskekropp er det balanse mellom de beinproduserende osteoblastene og beinnedbrytende osteoklastene. Lykkepillene ser ut til å forrykke denne balansen.

Forskerne har funnet ut at kroppens serotonin stimulerer osteoblastene slik at det foregår en sunn reproduksjon av beinceller. Dette kan være en av mekanismene som hindrer de fleste i å utvikle beinskjørhet.

Trolig permanente skader
Skader på skjelettet er generelt permanente. Det finnes ikke legemidler som kan reversere skader forårsaket av andre medikamenter. Man vet at lykkepiller ”bygges inn” i beinmassen. Studier viser at mengden av pillens ulike substanser i kroppen øker lang tid etter at pasienten har sluttet med legemiddelet.

Barn på lykkepiller opplever hemmet vekst, noe som også er skjelettrelatert.

Helsebombe?
Nordmenn har i utgangspunktet en svært høy forekomst av beinskjørhet. Og nå tar i tillegg hele 400 000 av oss lykkepiller. Vi kan i verste fall sitte på en helsebombe, der forekomsten av beinskjørhet øker betraktelig i årene som kommer.

Det er ikke forsket på langtidsvirkninger for beinmassen av SSRI-medikamenter. Ingen vet ennå hvor store skader lykkepiller kan medføre, eller hvor mange som kan være i faresonen. Men forskere i Nederland og i USA arbeider nå med å framskaffe slike data.

Skader på hjerteklaffene
NTNU-forskningen har også påvist en sammenheng mellom serotonin i blodet og skader på hjerteklaffene. Dette kalles det carcinoide syndrom. Gustafsson viser for første gang at overproduksjon av serotonin er direkte årsak til at skad