Serotonin syndrom (SS), kramper, parkinsonisme osv. (forhøyet kroppstemperatur)

Rykninger og kramper En 51 år gammel kvinne fikk utbetalt hele 2,2 millioner kroner i erstatning, etter at «lykkepiller» ga henne kroniske rykninger i ansiktet. (VG 22.05.2006)

- Sedan spred det sig så jag fick riktiga krampanfall i hela kroppen (tv4.se 12.11.2004)

Lexapro (Cipralex) Anna Nicole Smith’s 20-year-old son had been taking a common antidepressant... (intouchweekly.hollywood.com 19.9.2006)

Legemidler mot migrene og antidepressiva kan være en farlig kombinasjon (about.com 30.10.2007)

Ekstrem selvmordstendens som følge av serotonin syndrom
(Br J Psychiatry 1995;167:410)

Veteraner som tar PTSD-legemidler dør under søvn (wvgazette.com 25.5.2008)

En miks av legemidler kan være dødelig ...viser 7 349 tilfeller av serotonerg giftighet og 93 dødsfall (A Mix of Medicines That Can Be Lethal) (nytimes.com 27.2.2007)

Drug Packets Reportedly Found In Ledger's Home (wjz.com 23.1.2008)

Øker SSRI-preparater risiko for Parkinson og Alzheimers sykdom? (healthfinder.gov 27.4.2007)

Serotonin syndrom (serotonergt syndrom) underdiagnostiseres

Serotonin syndrom
nhi.no 22.6.2010
(...) Hva er serotonin syndrom?
Serotonin syndrom oppstår når du tar medisiner som forårsaker høye nivå av det kjemiske stoffet serotonin i kroppen din. Det kan skje når du øker dosen på et medikament som inneholder serotonin eller du starter med et nytt medikament i tillegg til dem du allerede tar. Visse illegale stoffer og kosttilskudd kan også utløse serotonin syndrom.

Serotonin er et kjemisk stoff som kroppen produserer og som behøves for at nervecellene og hjernen skal kunne fungere. Men for mye serotonin skaper problemer. Symptomer på serotonin syndrom spenner fra skjelvinger og diaré til alvorlige symptomer som muskelstivhet, feber og kramper. Alvorlig serotonin syndrom kan være fatalt dersom det ikke behandles. I de fleste tilfeller går et serotonin syndrom over av seg selv i løpet av et døgns tid dersom en stopper inntaket av medisinene som forårsaker symptomene, samt om nødvendig tar medisiner som blokkerer serotonin. (...)

Symptomer og tegn på serotonin syndrom
Symptomer på serotonin syndrom opptrer typisk innen minutter til få timer etter å ha tatt et nytt medikament, eller etter å ha økt dosen på et medikament du allerede bruker. Symptomer og tegn er oppfarenhet, uro, forvirring, rask puls, utvidete pupiller, tap av muskelkontroll, muskelkramper, sterk svette, diaré, hodepine, skjelvinger, gåsehud.

Alvorlig serotonin syndrom kan være livstruende. Tegn på alvorlig tilstand er høy feber, kramper, uregelmessig puls, bevisstløshet. (...)

Om å tenke utenfor boksen
Tidsskr Nor Legeforen 2010; 130:386 (25.2.2010)
Noen differensialdiagnoser er vanskeligere å huske på enn andre. Det kan være dem med uklare eller uspesifikke symptomer. Årsaken kan være at de er sjeldne eller at vi ikke er oppmerksomme nok. Fire ulike syndromer knyttet til sentralnervesystemet kan synes spesielt vanskelige å erkjenne. Ved siden av antikolinergt syndrom har vi akutt delirium, serotonergt syndrom og malignt nevroleptikasyndrom. Tenker vi ofte nok på disse potensielt dødelige tilstandene? (...)

(Anm: antikolinergt syndrom (SML-artikkel) (...) medisinsk forgiftningstilstand som er fremkalt av for sterk blokkering av signalsubstansen acetylkolin. Antikolinergt syndrom kan fremkalles ved overdosering av legemidler (nevroleptika, trisykliske antidepressiva) eller forgiftninger (f.eks. av fluesopp). Ved påvirkning av hjernen (sentralt syndrom) sees angst, uro, overaktivitet, forvirring, hallusinasjoner, muskelkramper og forstyrret hukommelse og orienteringsevne. Ved påvirkning av nervesystemet utenom hjernen (perifert syndrom) sees hjertebank, utvidede pupiller, varm og tørr hud, tørre slimhinner, vanskeligheter med vannlating og forstoppelse. Behandlingen består i fjerne årsaken (medikamentet) eller å tilføre motgift (fysostigmin). Kilde: Store norske leksikon.)

Doctors Fail to Recognize Life-Threatening Serotonin Syndrome (Leger mislykkes i å erkjenne livstruende serotonin syndrom)
opednews.com 4.5.2007
I tillegg til nylige rapporter om at legemidlene ikke virker bedre enn sukkerpiller, er det tilføyd en lang liste av uheldige hendelser linket til selektive serotoninreopptakshemmende antidepressiva som retter oppmerksomhet på fødselsdefekter, selvmord og vold. (In addition to recent reports that the drugs work no better than sugar pills, the latest warnings added to the long list of adverse events linked to selective serotonin reuptake inhibitor antidepressants have focused on birth defects, suicide risks and violence.)

Den massive overforskrivning av SSRI-er, som inkluderer Prozac, Seroxat (Paxil), Zoloft, Celexa (Citalopram) og Cipralex (Lexapro), har imidlertid i kombinasjon med mange andre legemidler medført at medisinske eksperter nå gir leger en slags informasjon om en livstruende tilstand kalt "serotonin syndrom". (...) (However, the massive over-prescribing of SSRIs, including Prozac, Paxil, Zoloft, Celexa and Lexapro in combination with many other drugs now has medical experts scrambling to educate doctors about a life-threatening condition known as "serotonin syndrome.")

Ifølge New York Times, ble det i 2005, det siste år statistikk er tilgjengelig, rapportert totalt 118 dødsfall. (...) (In 2005, the last year for which statistics are available, a total of 118 deaths were reported, according to the New York Times.)

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 (...)

Beskrivelse av serotonin syndrom

Serotonin syndrome
American Family Physician 1995;52:1475-82
Serotoninsyndrom er en potensielt livstruende komplikasjon grunnet psykofarmakologisk legemiddelterapi. Syndromet oppstår oftest ved samtidig bruk av ett eller flere legemidler som øker aktiviteten av serotonin i hjernestammen og blir ofte ikke oppdaget fordi det har en uspesifikk symptomatologi. Serotoninsyndrom er karakterisert ved en forandring i kognisjon, atferd, funksjonen av det autonome nervesystem og nevromuskulær aktivitet. (...) (Serotonin syndrome is a potentially lifethreatening complication of psychopharmacological drug therapy. The syndrome is produced most often by the concurrent use of two or more drugs that increase brainstem serotonin activity and is often unrecognised because of the varied and non-specific naure of its sympthomatlogy. Serotonin syndrome is characterized by alteration in cognition, bahavior, autonomic nervous system function and neuromuscular activity.)

Serotonin syndrom er en iatrogen forstyrrelse: Det opptrer kun ved legemiddelterapi som forøker serotoninnevrotransmisjonen i hjernen. Serotonin syndrom opptrer oftest når to eller flere serotonerge legemidler blir gitt samtidig. Men syndromet er også rapportert ved inntak av et enkelt legemiddel både ved terapeutisk bruk3 og ved overdose.4 (...) (Serotonin syndrome is an iatrogenic disorder: it only occurs in setting of drug therapy that has a net effect of augmenting brain serotonin neurotransmission. Serotonin syndrome most commonly occurs when two or more serotonergic are given concurrently. However, the syndrome has also been reprted with single drug exposure in both therapeutic settings3 and overdose setting.4)

Illustrerende tilfelle. En ellers sunn, men deprimert 18 år gammel mann opplevde en akutt alvorlig angst, sammentrekning av kjevemusklene, diffuse muskelsmerter, hodepine, karftig svetting, lysskyhet, vanskeligheter med å gå og hjertebank. Han klaget også på ukontrollerbar generell skjelving, rykninger og vridninger av hode. Symptomene startet omtrent to timer etter at han tok 20 mg av paroksetin (Seroxat). (...) (Illustrative Case. An otherwise healthy, but depressed, 18-year-old man experienced an acute onset of severe anxiety, jaw muscle tightness, diffuse muscle aches, headache, profuse sweating, photophofia, difficulty in walking and chest palpitations. He also complained of uncontrollable general shivering, leg twitches and head turning. His symptoms began approximately two hours after he took 20 mg of paroxetine (Paxil).)

Kort tid etter at symptomene startet ble pasienten undersøkt på sykehuslegevakten, hvor de fant at han var årvåken og orientert, men ekstremt redd. De vitale målinger viste en hjerterytme på 156 slag per minutt, blodtrykk på 172/111 mm Hg, åndedrettsrate på 28 per minutt og munntemperatur på 38,2 °C (100,8° F). Det var til stede en muskelstivhet, mest uttalt i de lavere ekstremiteter. Pupillene var 7 mm i diameter, med økt bilateral reaksjonsevne på lys. Det ble ikke observert nystagmus. De dype spenningsreflekser var diffust økt i både øvre og nedre ekstremiteter. Det kunne ses muskelrykninger bilateralt ved kne og ankler. Babinskis tegn var tilstede bilateralt. Rutinemessige blodprøver og elekrolytter var normale. (...) (Shortly after the onset of symptoms, the patient was evaluated in a hospital emergency department, where he was found to be alert and orientated but extremely apprehensive. Vital sign included heart rate of 156 beats per minute, blood pressure of 172/111 mm Hg, respiratory rate of 28 per minute and oral temperature of 38,2 °C (100,8° F). Diffuse musclel rigidity was present but was more pronounced in the lower extremeties. Pupils was 7 mm in diameter, with increased light reflex bilaterally. Nystagmus was not observed. Deep tendon reflexes were diffusely increased in both upper and lower extremities. Clonus was elicited bilaterally at the knee and ankle. Babinski’s sign was present bilaterally. Routine blood studies and electrolytes was normal.)

De nevromuskulære klager innbefattet rastløshet, ufrivillige rykkevise muskelrykninger (selv i søvne), tremor i ekstremiteter i hvile, tannklapring og ustødig gange. (...) (Neuromuscular complaints include restlessness, involuntary myoclonic jerks (even than sleeping), resting extremety tremor, teeth chattering and diffuse walking.)

Serotonin Syndrome: A Clinical Update (Serotoninsyndrom: En klinisk oppdatering)
Crit Care Clin 1997;13:763-83
(...) I sin mest alvorlige form utvikler SS seg hurtig til hjertestopp, koma eller multippel organsvikt, med disseminert intravaskulær (DIC).”… (In its most severe presentation, SS rapidly progresses to cardiac arrest, coma seizures, or multiple organ failure with disseminated intravascular coagulation.)

Ikke desto mindre kan SS klart bli livstruende og i noen tilfeller har dødsfall opptrådt til tross for tidlig og aggressiv behandling.10,15,36,37,85,106,110”… (Nonetheless, SS can clearly become life-theatening and in some cases deaths have occurred despite early and aggressive intensive care.10,15,36,37,85,106,110)

SS er en iatrogen legemiddelrelatert lidelse som ikke har noe kjent endogent motstykke. Det eksisterer kun som et direkte resultat av psykofarmakologisk legemiddelterapi. Den første redegjørelse for SS er en case-rapport publisert i 1955 hvor toksisk hjernebetennelse diskuteres. (...) (SS is an iatrogenic drug-related disorder that has no known endogenous counterpart. It exists only as a direct result of psychopharmacologic drug therapy. The earliest published account of SS is attributed to a 1955 case report discussing toxic encephalitis.73.)

Det eneste absolutte konsistente funnet blant tilfeller av SS er at pasienten har inntatt et legemiddel eller en kombinasjon av flere som øker serotoninaktiviteten i sentralnervesystemet (CNS). (...) (The The only absolutely consistent finding among cases of SS is the history of patient exposure to a drug or combination of drugs that increase CNS serotonin activity.)

SS er ikke relatert til kjønn og har blitt rapportert hos pasienter i alderen fra 9 (55) til 82 år.29 SS er idiosynkratisk i sin natur. Pasienter er ikke mer tilbøyelige å utvikle SS som følge av en overdose enn de er ved inntak av terapeutiske doser. I tilfeller hvor legemiddelnivåer er bestemt (iberegnet metabolitter), har nivåene vært terapeutiske eller lavere enn terapeutiske nivåer i 80 % til 90 % av tilfellene. Derfor ekskluderer ikke terapeutiske nivåer denne diagnosen. SS er blitt rapportert ved terapeutisk inntak av ett enkelt legemiddel; i kombinasjon med flere legemidler (85 % av tilfellene); overdose med ett enkelt legemiddel; overdose ved polyfarmasi; og misbruk av illegale midler. (...) (SS does not have a gender predilection and has been reported in patients ranging in age from 9 (55) to 82 years old.29 SS is idiosyncratic in nature. Patients are no more likely to develop SS following an overdose than they are while taking therapeutic doses. In cases where drug levels have been determined (including metabolites), drug levels have either been at therapeutic or below therapeutic levels in 80% to 90% of cases. Therefore, therapeutic drug levels do not exclude the diagnosis. SS has been reported in association with singel-drug therapy; combination-drug therapy (85% of cases); single-drug overdose; polydrug overdose; and recreational drug of abuse.)

SS kan teoretisk forårsakes av ethvert legemiddel eller kombinasjon av legemidler som effektmessig kan øke den serotonerge neurotransmisjon (Fig. 2). Dyremodeller for SS tyder på at det primært først og fremst opptrer via stimulering av postsynaptiske 5-HT1A reseptorer i hjernestammen.43,99,105. I tillegg er stimulering av postsynaptisk 5-HT2 reseptorer sannsynligvis også involvert selv om det er mindre viktig enn 5-HT1A reseptorer i forklaringen av hele SS37,45. (...) (SS can theoretically be produced by any drug or combination of drugs that has the net effect of increasing serotonergic neurotransmission (Fig. 2). Animal models of SS suggest that it primarily occurs via stimulation of postsynaptic 5-HT1A receptors in the brain stem.43,99,105. In addition, stimulation of postsynaptic 5-HT2 receptors, although less important than 5-HT1A reseptors, is probably also involved in explaining the full SS37,45.)

Tabell 1. SEROTONERGT POTENSIAL FOR FORSKJELLIGE MIDLER (utdrag) (Table 1. SEROTONERIGIC POTENTIAL OF VARIOUS DRUGS)

	Høyt	Middels	Lavt	Ikke

Klomipramin	x
Kokain		x
Deksfenfluramin	x
Fenfluramin	x
Fluoxetine (fluoksetin	x
Fluvoxamine (Fluvoksamine)	x
L-Dopa		x
LSD		x
Litium	x
MDMA	x
Melatonin			x
Meperidin	x
Moklobemid	x
Morfin				x
Nefazadon			x
Nortriptylin		x
Paroksetin	x
Seleglin	x
Sertralin	x
Trazodon		x
Venlafaksin	x

Midler som misbrukes, slik som 3,4-metylenedioksimetamfetamin (MDMA, ecstasy)15,27,97 og kokain, kan begge øke utløsningen av serotonin og blokkere opptaket. (...) (Drugs of abuse, such as 3,4-methylenedioxymethaphetamine (MDMA, ecstasy)15,27,97 and cocaine can both increase the release of serotonin and block it’s uptake.)

Rhabdomyolosis kan resultere i forlenget eller alvorlig muskelstivhet. Utbredt skjelving opptrådte i omtrent 25 % av innrapporterte tilfeller. Nystagmus og Babinskis tegn (respons fra strekkmuskler) er blitt rapportert med tilsvarende frekvens og har alltid vært bilateral. Mindre vanlig er nevromuskulære abnormaliteter som klapring av tenner, parestesi og ”hodevridninger”. (...) (Rhabdomyolosis can result from either prolonged or severe muscle rigidity. Generalized shivering occured in approximately 25% of reported cases. Nystagmus and Babinski’s sign (extensor response) have been reported with equal frequency and have always been bilateral. Less commonly reported neuromuscular abnormalities include teeth chattering, paresthesias, and head twitching.)

Atferdsforandringer, slik som angst og hypomani, kan til å begynne med bli feiltolket som akutt forverring av underliggende psykiatrisk sykdom. Anfall/kramper har inntruffet i 14 % av innrapporterte tilfeller med utbredte tonisk-kloniske kramper. De er vanligvis av kort varighet, men langvarige kramper er blitt rapportert36,58,79,101. Subjektive symptomer, slik som hodepine, søvnløshet, hallusinasjoner (visuelle) og svimmelhet, er mindre vanlig. (...) (Changes in behavior, such as anxiety and hypomania, may be initially misinterpreted as an exacerbation of underlaying psychiatric illness. Sizures have occured in 14% of reported cases and are generalized tonic-clonic in nature. They are usually short-lived, but refractory convultions have been reported36,58,79,101. Subjective symptoms, such as headache, insomnia, hallucinations (visual), and dizziness, are less commonly, elicited.)

vetting er et av kjennetegnene ved SS og er innrapportert i omtrent halvparten av tilfeller beskrevet i litteraturen. (...) (Diaphoresis is one of the hallmarks of SS and is reported in approximately half of all cases found in literature.)

Utvidede pupiller er blitt observert i omtrent en fjerdedel av rapporterte tilfeller, og har ikke reagert på lys. Rødming, diaré, økt spyttsekresjon og magesmerter opptrer relativt ”sjelden”. (...) (Dilated pupils have been seen in over a quarter of reported cases and have been unreactive to light. Flushed skin, diarrhea, salivation, and abdominal pain occure relatively infrequently.)

SS er assosiert med mange potensielt alvorlige komplikasjoner, slik som hypertermi, anfall/kramper, koma, disseminert intravaskulær koagulasjon (DIC), for lavt blodtrykk, ventrikulær takykardi og metabolsk acidose. (...) (SS is associated with many potentially severe complications, such as hyperthermia, seizures, coma, disseminated intravascular coagulation, hypotension, ventricular tachycardia, and metabolic acidosis.)

Metabolsk acidose er typisk påvist bare i tilfeller som involverer hypertermi, anfall/kramper, muskelstivhet eller multippel organsvikt. (...) (Metabolic acidosis is typically seen only in cases involving hyperthermia, seizures, muscle rigidity, or multiple organ failure.)

(Anm: metabolic acidosis; metabolsk acidose; syreopphoping pga sure stoffskifterestar; jf ketoacidose, mjølkesyreacidose; metabolsk acidose er også ein del av uremitilstanden; jf anion gap. EN metabolic acidosis. Kilde: Norsk medisinsk ordbok.)

(Anm: Metabolsk acidose er når syrebase-balansen (pH-nivået) i kroppsvæsken er for surt. Dette fenomenet ses særlig hos diabetikere og personer med nyresvikt. Endringer i bikarbonat-konsentrasjonen (base, alkali) er den primære årsaken til denne forstyrrelsen1,2. Normalt skal kroppsvæskene ha et pH-nivå på ca. 7,4. Ved høyere verdier (f.eks. 7,6) foreligger alkalose og ved lavere verdier (f.eks. 7,2) foreligger acidose. Metabolsk acidose skyldes at ulike kjemiske prosesser i kroppen medfører opphopning av syre. Manglende utlufting av avfallsgassen CO2 via lungene, gir også acidose, men da kalles det respiratorisk acidose, det vil si at årsaken er sviktende lungefunksjon. (nmi.no).)

Ekstrem selvmordstendens som følge av serotonin syndrom

Extreme suicidality following serotonin syndrom (Ekstrem selvmordstendens som følge av serotonin syndrom)
British Journal of psychiatry 1995;167:410
(...) Dette tilfellet tyder på at det, som et resultat av serotonin syndrome, kan ha oppstått økt sensitivitet selv ved forsiktig reintroduksjon av et legemiddel med serotonerge egenskaper (clomipramine). Selv om serotonin syndrom er sjelden forekommende, er det påkrevet at pasienter nøye følges i tiden etter at TSS er påvist”. (...) (This case suggests that, following serotonin syndrome, increased sensitivity to even cautious reinstatement of a drug with serotonergic properties (clomipramine), may occur. Although the serotonin syndrome is rare, careful study of patients in the aftermath of TSS is indicated.)

Hun gjorde gjentagende forsøk på å skade seg selv, og forsøkte å innta ulike objekter, mens hun uttalte ”Jeg føler meg så fryktelig dårlig at jeg vil dø” (...) (She made continues effort to lacerate herself and tried to ingest various objects, stating ”I feel so awful I must die”.).

(Anm: TSS: Toxic Serotonin Syndrome).

- Dødsfall grunnet serotonin syndrom etter inntak av Seroxat (paroxetine; paroksetin)

Serotonin syndrome after a massive overdose of controlled-release paroxetine.
Psychosomatics. 2010 Sep;51(5):437-42.
BACKGROUND: Serotonin syndrome is a condition resulting from an overabundance of serotonin at postsynaptic receptors. The syndrome usually responds to cyproheptadine and benzodiazepines. However, some patients do not respond to conventional treatment. (...)

RESULTS: The patient had initially presented with minor symptoms of serotonin syndrome, but these quickly progressed in severity, and he eventually died from resulting complications: a pulmonary embolism 9 days after admission, despite appropriate prophylaxis with enoxaparin.

CONCLUSION: The authors are the first to report on a paroxetine overdose of this magnitude, and they provide one of the few reports on a prolonged course of serotonin syndrome that was unresponsive to standard treatment. (...)

- Seroxat-dødsfall grunnet serotonin syndrom og hypertermi

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

- Metabolsk acidose og generaliserte epileptiske anfall sekundært ved overdose av citalopram: en caserapport

Metabolic acidosis and generalized seizures secondary to citalopram overdose: a case report. (Metabolsk acidose og generaliserte epileptiske anfall sekundært ved overdose av citalopram: en caserapport)
J Clin Pharm Ther. 2010 Aug 1;35(4):479-82.
Selective serotonin re-uptake inhibitors (SSRIs) are widely used in the community for treating many forms of mental illnesses. Citalopram, a newer generation SSRI, is commonly prescribed, but despite its low toxicity profile has a potential to cause seizures and dysarrythmias in overdose. Data on citalopram overdose-induced metabolic acidosis are scarce. There have been only three cases of metabolic acidosis reported in the literature due to citalopram overdose in humans and we are reporting the fourth one. We report a case of citalopram overdose with metabolic acidosis and generalized seizure. To our best knowledge, this is the first case reported in Saudi Arabia. (...)

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.)

SSRIer og giftighet

Toxicity, Selective Serotonin Reuptake Inhibitor
emedicine.com 18.5.2007
(...) The most serious drug-related adverse effect of SSRIs is the potential to produce serotonin syndrome (SS). Commonly prescribed SSRIs include sertraline (Zoloft), fluoxetine (Prozac), paroxetine (Paxil), and fluvoxamine (Luvox).

SS, characterized by mental status changes, neuromuscular dysfunction, and autonomic instability, is thought to be secondary to excessive serotonin activity in the spinal cord and brain.

Initial reports of such a syndrome date back to the 1950s; however, the full spectrum of the syndrome has only recently been appreciated. Increased use of SSRIs for a variety of neurobehavioral disorders has led to a greater clinical awareness of the syndrome. (...)

Frequency:
• In the US: Data from the 2004 annual report of the American Association of Poison Control Centers Toxic Exposures Surveillance System (AAPCC-TESS) reveal that 48,204 SSRI exposures (from a total of 103,155 antidepressant exposures) occurred; 11,680 exposures to SSRIs occurred in children aged 6-19 years, and 8187 exposures occurred in children younger than 6 years. (...)

History: SSRIs have a high toxic-to-therapeutic ratio, and fatalities are uncommon with pure SSRI overdoses. Because the enteric nervous system is richly innervated by serotonin, acute toxicity is frequently manifested by altered gastrointestinal motility and nausea. The most serious drug-related adverse effect of SSRI is the potential to produce SS. (...)

DIFFERENTIALS Section 4 of 10

Author Information Introduction Clinical Differentials Workup Treatment Medication Follow-up Miscellaneous Bibliography

Hyperthyroidism
Substance Abuse: Cocaine
Tetanus
Toxicity, Hallucinogens - LSD
Toxicity, Hallucinogens - PCP
Toxicity, Monoamine Oxidase Inhibitor
Toxicity, Tricyclic Antidepressant (...)

Other Problems to be Considered:
NMS
Hyperthermia (...)

Lab Studies:
• Rapid bedside glucose determination
• Serum pH
• Electrolytes, including calcium, magnesium, and phosphorus: Check for anion gap acidosis that may be present in co-ingestions.
• Serum salicylate and acetaminophen levels
• Creatine kinase (CK)
• Urinalysis and urine toxicological screen
• Urine pregnancy test when indicated
• Serotonin and 5-hydoxyindolacetic acid measurement: Although serotonin and its metabolite (5-hydroxyindolacetic acid) can be measured, this data would not be readily available and, therefore, would have limited clinical utility. (...)

Serotonin og aggresjon

Reduced serotonin 5-HT1A receptor binding in the temporal cortex correlates with aggressive behavior in Alzheimer disease
Brain Res. 2003 Jun 6;974(1-2):82-7
Previous studies have implicated brain serotonin 5-HT(1A) receptors in several CNS functions, including cognition, mood and emotional states. In Alzheimer disease (AD), cognitive impairment and behavioral symptoms are the main clinical features. However, the biochemical basis of such changes is poorly understood. Results from recent in vivo studies suggest that 5-HT(1A) receptors may be related to aggressive traits in healthy subjects. The present study investigated the state of 5-HT(1A) receptors in the postmortem neocortex of 33 AD patients prospectively assessed for cognition and behavioral symptoms, together with 20 matched controls, by saturation [(3)H]8-OH-DPAT binding assays. 5-HT(1A) receptor binding affinity (K(D)) and density (B(max)) were unchanged in the overall AD group compared with controls. Within the AD group, 5-HT(1A) receptor B(max) in the temporal cortex inversely correlated with aggression and dementia severity. However, multiple regression analyses showed that 5-HT(1A) receptor B(max) remained the best predictor for aggression, while temporal cortical neurofibrillary tangle grading was the best predictor for dementia severity. This suggests that 5-HT(1A) receptor alteration is directly related to aggression in AD, while dementia severity is more strongly related to the neurodegenerative process. Our data indicate further study of 5-HT(1A) receptors as a pharmacological target for the treatment of behavioral symptoms in AD. (...)

Zyprexa – ökad förekomst av cerebrovaskulära händelser (stroke och TIA) och ökad dödlighet i demensstudier
mpa.se 9.3.2004
Risperdal – förnyad aktualitet för tidigare information om ökad förekomst av cerebrovaskulära händelser i demensstudier
mpa.se 9.3.2004

PDR (Final labelling paroxetine)
fda.gov
(...) Kardio-vaskulære system: "frequent": forhøyet blodtrykk, besvimelse, takykardi; "infrequent": bradykardi, forstyrrelser i overføringen av impulser i hjertets ledningssystem, unormalt elektrokardiogram, lavt blodtrykk, migrene, forstyrrelse i perifer blodsirkulasjon; "rare": angina pectoris, arytmi, atrieflimmer, blokkert overledning i en del av hjertets ledningssystem, dårlig blodtilførsel til hjernen, hjerneslag, plutselig, sykelig forandring i hjernen på grunn av sirkulasjonsforstyrrelser (hjerneslag), hjertesvikt med opphopning av blod i deler av kretsløpet, lavt minuttvolum fra hjertet, hjerteinfarkt, forstyrrelse i blodforsyningen til hjertemuskelen, blekhet, betennelse i blodåre, lungeemboli, ekstraslag i hjertet forårsaket av elektriske impulser generert i atriene, trombose, sykelig utvidet vene, hodepine på grunn av sirkulasjonsforhold, ekstraslag i hjertet forårsaket av elektriske impulser generert i ventriklene. (Cardiovascular System: frequent: hypertension, syncope, tachycardia; infrequent: bradycardia, conduction abnormalities, electrocardiogram abnormal, hypotension, migraine, peripheral vascular disorder; rare: agina pectoris, arrhythmia, atrial fibrillation, bundle branch block, cerebral ischemia, cerebrovascular accident, congestive heart failure, low cardiac output, myocardial infarct, myocardial ischemia, pallor, phlebitis, pulmonary embolus, supraventricular extrasystoles, thrombosis, varicose vein, vascular headache, ventricular extrasystoles.)

TIA - Transitorisk ischemisk attack
viss.nu
(övergående syrebrist)
Definieras som neurologiska bortfall på basen av ischemi med kortare duration än 24 timmar. De flesta TIA har endast högst timslång duration. Malign TIA eller hopade TIA betyder två eller fler TIA inom de närmast föregående två veckorna och är ett hotfullt tillstånd.

TIA-attacker i allmänhet, innehåller oftast motoriska bortfallssymtom. Ett undantag utgör amaurosis fugax som oftast uppträder utan andra symtom. Patienter med enbart sensoriska symtom måste bedömas med stor försiktighet innan diagnosen TIA fastställs.

Nedan symptom är inte typiska för TIA:
- sensoriska symptom som successivt vandrar ex från handen till under- resp överarmen
- blås- eller tarminkontinens
- synförlust i samband med medvetanderubbning
- fokala symptom i samband med migrän
- enbart konfusion
- enbart minnesförlust
- enbart drop-attacker
Nedan symptom skall inte benämnas TIA:
- medvetslöshet utan andra
tecken på cirkulationsrubbning
i vertebrobasilaris-området
- toniska och/eller kloniska kramper
- symptom som successivt
breder ut sig i flera områden
av kroppen
- flimmerskotom

Serotonergt syndrom med dødelig utgang utløst av selektiv serotonin opptakshemmer
Tidsskr Nor Lægeforen 1999; 119: 647-50
(...) Serotonergt syndrom er en sjelden, men potensielt dødelig bivirkning av medikamenter som øker serotonerg neurotransmisjon. I takt med økt bruk av selektive reeopptakshemmere må vi forvente å se tilstanden hyppigere. Syndromet karakteriseres av forandret mental status med uro, konfusjon, og agitasjon, videre neuromuskulære symptomer som skjelvinger, myoklonus ataksi og hyperrefleksi. Dessuten sees autonome symptomer med feber, svette hypertensjon og takykardi. Årsaken er oftest interaksjon mellom ulike medikamenter, men syndromet kan opptre ved monoterapi, selv i terapeutiske doser. Vi beskriver et tilfelle med dødelig utgang etter inntak av paroxetin (Seroxat) i terapeutiske doser. (...)

Tilstanden kan imidlertid utvikle seg raskt, med dramatisk forverring av symptomene i løpet av timer. Årvåkenhet for symptomer er viktig for å unngå fatal utgang. (...)

Avgjørende for diagnosen er det utløsende medikament. Det verdt å merke seg at serumnivå av medikament oftest er i normalområdet (5). Forhøyet nivå er ikke et diagnostisk kriterium.

The toxicity of antidepressant poisoning: is it changing? A comparative study of cyclic and newer serotonin-specific antidepressants
Emerg Med (Fremantle). 2002;14:440-6)
MÅLSETTING: Å sammenlikne kliniske trekk for cycliske antidepressiva og nyere, ikke-cycliske, serotonin- spesifikke antidepressiv forgiftning. METODE: Sammenlignende, beskrivende studie av alle antidepressive overdose pasienter innlagt på et sykehus grunnet toksisitet fra februar 1997 til april 2001. Pasient data ble registrert prospektivt i en reservert toksikologisk database for subsequent analyse. (AIM: To compare the clinical features of cyclic antidepressant and newer, non-cyclic, serotonin-specific antidepressant poisoning. METHODS: Comparitive, descriptive study of all antidepressant overdose patients admitted to a hospital toxicology service from February 1997 to April 2001. Patient data were entered prospectively into a dedicated toxicology database for subsequent analysis.)

RESULTATER: Der var 256 innleggelser for antidepressiv forgiftning (17,5 % av alle innleggelsr grunnet forgiftning). Cykliske forgiftning med antidepressiva omfattet 43 % av antidepressiva innleggelser. Statistisk signifikante forskjeller mellom de to grupper inkluderte cycliske antidepressiva grupper hadde lenger median opphold (23,1 vs 15,9 h, P = 0.0008), større behov for endotrakeal intubasjon (31 % vs 4%, OR = 11,5, P < 0.0001) og høyere forekomst av anfaløl (7,2 % vs 0,7%, OR = 10.4, P = 0.01), hurtifgere median puls, lenger QRS-intervall ved innleggelse, og lenger intensiv opphold. Imidlertid, ikke-cycliske, serotonin-specifikke antidepressiv forgiftning involverte høyere doser av antidepressiva og var mer sannsynlig å ha inntatt andre legemidlker sammen med disse. Serotonin syndrom vart den eneste registrerte ikke-cycliske, serotonin-specifikke forgiftning (10,3 %, OR = 26.6, P = 0.0002). Patienter med serotonin syndrom hadde lenger median sykehusopphold (46 vs 16 h, P < 0.0002) sammenliknet med andre ikke-cycliske, serotonin-spesifikke pasiewnter. Der var ingen dødsfall i løpet av studieperioden. (RESULTS: There were 256 admissions for antidepressant poisoning (17.5% of all poisoning admissions). Cyclic antidepressant poisoning comprised 43% of antidepressant admissions. Statistically significant differences between the two groups included: cyclic antidepressant group had longer median length of stay (23.1 vs 15.9 h, P = 0.0008), greater need for endotracheal intubation (31% vs 4%, OR = 11.5, P < 0.0001) and higher incidence of seizures (7.2% vs 0.7%, OR = 10.4, P = 0.01), faster median pulse rate, longer QRS-interval on admission, and longer intensive care unit stays. However, non-cyclic, serotonin-specific antidepressant poisonings involved larger doses of antidepressants and were more likely to ingest other medications along with these. Serotonin syndrome was only seen in non-cyclic, serotonin-specific poisoning (10.3%, OR = 26.6, P = 0.0002). Patients with serotonin syndrome had a longer median hospital stay (46 vs 16 h, P < 0.0002) compared to other non-cyclic, serotonin-specific patients. There were no deaths during the study period.)

KONKLUSJONER: Cycliske antidepressiva omfatter fremdeles en signifikant andel av antidepressiv forgiftning og resultere i mmer signifikant sykelighet enn ikke-cyclisk, serotonin-spesifikk forgiftning. Klinikere bør også være oppmerksom på at ikke-cycliske, serotonin-spesifikk forgiftning kan resultere i utviklingen av serotonin syndrom. Det ar den mest signifikante giftige effekten registert som følge av ikke-cyckisk, serotonin-spesifikk forgiftning i denne studien.” (CONCLUSIONS: Cyclic antidepressants still comprise a significant proportion of antidepressant poisoning and result in more significant morbidity than non-cyclic, serotonin-specific poisoning. Clinicians should also be aware that non-cyclic, serotonin-specific poisoning may result in the development of serotonin syndrome. This was the most significant toxic effect noted following non-cyclic, serotonin-specific poisoning in this study.)

Antidepressant-Induced Adverse Reactions in a Patient with Hemorrhagic Stroke (October)
Ann Pharmacother. 2005 Aug 9; [Epub ahead of print]

Antidepressant-Induced Adverse Reactions in a Patient with Hemorrhagic Stroke (October).

OBJECTIVE: To report a case of antidepressant-induced adverse drug reactions in a patient with hemorrhagic stroke. CASE SUMMARY: A 56-year-old man developed life-threatening adverse reactions after fluoxetine was added to his previously prescribed regimen of buspirone and olanzapine. One week after starting fluoxetine 60 mg/day, the patient developed syndrome of inappropriate antidiuretic hormone secretion and serotonin syndrome concurrently. The patient had experienced a hemorrhagic stroke before the adverse drug reactions occurred. DISCUSSION: A patient with a history of hemorrhagic stroke developed serious adverse drug reactions when fluoxetine was added to his drug therapy. When the combination therapy was stopped, all adverse effects gradually disappeared and laboratory abnormalities were corrected. The likelihood that the adverse reactions were caused by fluoxetine is probable according to the Naranjo probability scale. In addition, a history of stroke may be a risk factor for the development of such reactions. CONCLUSIONS: Today, patients with depression after experiencing a stroke are treated more effectively, but antidepressant-induced adverse drug reactions may be serious. A growing number of patients are treated for post-stroke depression; they require close supervision and careful dosing of antidepressants to prevent full-blown adverse reactions from occurring. (...)

En miks av legemidler kan være dødelig

A Mix of Medicines That Can Be Lethal (En miks av legemidler kan være dødelig)
nytimes.com 27.2.2007
The death of Libby Zion, an 18-year-old college student, in a New York hospital on March 5, 1984, led to a highly publicized court battle and created a cause célèbre over the lack of supervision of inexperienced and overworked young doctors. But only much later did experts zero in on the preventable disorder that apparently led to Ms. Zion’s death: a form of drug poisoning called serotonin syndrome. (...)

When she became agitated, a symptom of serotonin toxicity, and tried to pull out her intravenous tubes, she was restrained, and the resulting muscular tension is believed to have sent her fever soaring to lethal heights.

Now, with the enormous rise in the use of serotonin-enhancing antidepressants, often taken in combination with other drugs that also raise serotonin levels, emergency medicine specialists are trying to educate doctors and patients about this not-so-rare and potentially life-threatening disorder. In March 2005, two such specialists, Dr. Edward W. Boyer and Dr. Michael Shannon of Children’s Hospital Boston, noted that more than 85 percent of doctors were “unaware of the serotonin syndrome as a clinical diagnosis.”

In their review in The New England Journal of Medicine, Dr. Boyer and Dr. Shannon cited a report based on calls to poison control centers around the country in 2002 showing 7,349 cases of serotonin toxicity and 93 deaths. (In 2005, the last year for which statistics are available, 118 deaths were reported.)

The experts fear that failure to recognize serotonin syndrome in its mild or early stages can result in improper treatment and an abrupt worsening of the condition, leading to severe illness or death. Even more important, in hopes of preventing it, they want doctors — and patients — to know just what drugs and drug combinations can cause serotonin poisoning.
(...)

A Diagnostic Challenge
Serotonin syndrome was first described in medical literature in 1959 in a patient with tuberculosis who was treated with meperidine. But it wasn’t given its current name until 1982.

Recognizing the early signs is tricky because it has varying symptoms that can be easily confused with less serious conditions, including tremor, diarrhea, high blood pressure, anxiety and agitation. The examining physician may regard early symptoms as inconsequential and may not think to relate them to drug therapy, Dr. Boyer and Dr. Shannon noted.

In its classic form, serotonin syndrome involves three categories of symptoms:
Cognitive-behavioral symptoms like confusion, disorientation, agitation, irritability, unresponsiveness and anxiety.

Neuromuscular symptoms like muscle spasms, exaggerated reflexes, muscular rigidity, tremors, loss of coordination and shivering.

Autonomic nervous system symptoms like fever, profuse sweating, rapid heart rate, raised blood pressure and dilated pupils.

Widespread ignorance of the syndrome is another diagnostic impediment. But even when doctors know about it, the strict diagnostic criteria may rule out “what are now recognized as mild, early or subacute stages of the disorder,” Dr. Boyer and Dr. Shannon wrote. (...)

Perhaps adding to the diagnostic challenge is the fact that a huge number of drugs — prescription, over the counter, recreational and herbal — can trigger the syndrome. In addition to selective serotonin reuptake inhibitors like Zoloft, Prozac and Paxil and serotonin/norepinephrine reuptake inhibitors like Effexor, the list includes tricyclic antidepressants and MAOIs (for monoamine oxidase inhibitors); narcotic painkillers like fentanyl and tramadol; over-the-counter cough and cold remedies containing dextromethorphan; the anticonvulsant valproate; triptans like Imitrex used to treat and prevent migraines; the antibiotic Zyvox (linezolide); antinausea drugs; the anti-Parkinson’s drug L-dopa; the weight-loss drug Meridia (sibutramine); lithium; the dietary supplements tryptophan, St. John’s wort and ginseng; and several drugs of abuse, including ecstasy, LSD, amphetamines, the hallucinogens foxy methoxy and Syrian rue. (...)

Serotonin syndrome can occur at any age, including in the elderly, in newborns and even in dogs. Since 1998, the poison control center at the American Society for the Prevention of Cruelty to Animals has gotten more than a thousand reports of the ingestion of antidepressant medications by dogs, which can develop symptoms rapidly and die. The syndrome can also occur weeks after a serotonin-raising drug has been discontinued. Some drugs remain active in the body for weeks, and the MAOIs disable an enzyme involved in serotonin metabolism that does not recover until weeks after the drugs are stopped. (...)

(Anm: The serotonin syndrome. N Engl J Med. 2005 Mar 17;352(11):1112-20.)

Warning issued over drug
canada.com 27.2.2007
Overdose of B.C.'s most widely prescribed antidepressant can cause seizure, death, official says (...)

"We are alerting doctors about our concerns to give them a heads-up that it is a potential concern because it appears it is more toxic than it was originally hoped it would be," Derek Daws, managing director of the B.C. Drug and Poison Information Centre said in an interview Monday, referring to the medication called venlafaxine, whose brand name is Effexor. (...)

The drug, a serotonin and norepinephrine reuptake inhibitor (SNRI) has been available in Canada since 1994 and was initially thought to have a safer overdose profile than other antidepressant drugs. (...)

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

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

Anna Nicole Smith told pal she couldn't 'go on'
dailyindia.com 11.2.2007
(...) Smith's pal also revealed that the model was on anti-depressants Xanax and Prozac plus slimming pills and strong pain-killers.

"She took the anti-depressants just so she could get up in a morning and she didn't always take them according to the directions. She'd just slug a couple down if she was getting anxious," the pal said. (...)

Two dead after fatal mix of prescription drugs
townsvillebulletin.news.com 13.11.2006
TWO men died and more became severely ill after a man incited them to take a mixture of two prescription pills, claiming it would give them a "high", police believe. (...)

A post-mortem found Mr Bateson had died from "serotonin syndrome" caused by ingesting two anti-depressants: venlafaxine (brand name Effexor) and moclobemide (Aurorix). (...)

Deprimerade patienter misstros av vården
tv4.se 12.11.2004
Karin Sörensen fick kramper men misstroddes av läkarna.

Patienter blir inte trodda när dom berättar om sina biverkningar av antidepressiva medel - som att de får självmordstankar, blir apatiska och känner sig beroende av medicinen. (...)

Karin Sörensen är av de drabbade
- Bemötandet var det värsta. Att inte bli trodd av läkarna. De sade att den här medicinen kommer att fungera, men sen när den inte fungerade så sade de aha, men då är det något annat än medicinen, säger hon. (...)

- Sedan spred det sig så jag fick riktiga krampanfall i hela kroppen. Och när jag talar om det för läkare så sade de att det kan inte vara medicinen men jag slutade med den och sen har jag aldrig haft krampen igen. (...)

Dementeras av läkare
Kilen är en intesseorganisation dit konsumenter kan rapportera läkemedelsbiverkningar. Många är desperata när de ringer om biverkningar som dementeras av läkare, trots att biverkningarna ibland finns nämnda i Fass, uppslagsboken för läkemedel.

- Det här är ju oerhört förvirrande för en patient att det står i Fass trots att doktorn säger att det inte är det. Och då förlorar man förtroendet för läkaren, man förlorar förtroendet för läkemedlet och man slutar en behandling som kanske kunnat hjälpa, säger Jan Albinson på Kilen. (...)

Lyckopiller får många att må ännu sämre
tv4.se 11.11.2006
Över en halv miljon svenskar använder antidepressiva läkemedel, så kallade lyckopiller. Men mer än hälften måste byta medicin för att biverkningarna är för svåra. (...)

Kända biverkningar är illamående, sexualstörningar och känslan av vara avskärmad från omgivningen. (...)

Watch for overdoses for antidepressant Effexor, U.S. urges
cbc.ca 25.10.2006
(...) The overdoses were most common when the drug was taken with alcohol or other drugs, the agency said.

Doctors should prescribe the "smallest quantity of capsules consistent with good patient management," the FDA said in releasing a letter from Wyeth.
The letter did not say how many overdoses have been reported. The most commonly reported events in overdoses were a faster-than-normal heart rate, changes in level of consciousness, widening of the pupils, seizures and vomiting. (...)

Antidepressant overdoses can be potentially fatal. The risks with Effexor may be higher than other selective serotonin reuptake inhibitors such as Prozac, Zoloft and Paxil, but less than with older antidepressants called tricyclics, the company said. (...)

Earlier this year, Health Canada warned women taking SSRIs who are pregnant or thinking of becoming pregnant that the drugs may carry potential risks to the baby.

Internal Links
Health Canada issues antidepressant warning for pregnant women
External Links
Wyeth letter to doctors, U.S. FDA (in .pdf format) (...)

Prozac plus Ecstasy a toxic combo
reuters.com 21.9.2006
- The combination of the antidepressant drug Prozac and the illegal "club drug" Ecstasy increases the risk of acute toxic effects of Ecstasy, and may explain the increasing number of Ecstasy-related deaths, according to research presented at the annual meeting of the American College of Clinical Pharmacology, held here this week. (...)

Troops With Stress Disorders Fit For Duty?
cbsnews.com 19.10.2006
(...) Meanwhile, Bryce Syverson is still in Iraq. He sent this e-mail home:

"Head about to explode from the blood swelling inside, the lightning storm that happened inside my head."

He wrote that it was the anti-depressants that were making him feel bad, so he told his father he may stop taking them.

"Who knows what could happen? There are soldiers depending on him, and other soldiers are expecting Bryce to react," his father says. "Who knows how he will react under live combat fire." (...)

THE DRUGS BEHIND DANIEL’S DEATH
intouchweekly.hollywood.com 19.9.2006
Anna Nicole Smith’s 20-year-old son had been taking a common antidepressant and a sleeping pill, and a combination of the two could have been behind his death, In Touch has learned exclusively.

Daniel Smith had prescriptions for both the insomnia drug Ambien and the antidepressant Lexapro for two months and the buildup over the weeks could have been just too much for his body to handle. Pharmacist Jennifer Athay tells In Touch a cocktail of the two drugs can be fatal. “There are cases where people have died,” she says.

Dr. Cyril Wecht, the pathologist brought in by Anna Nicole to conduct a second autopsy, says Daniel’s depression “had to do with a girlfriend.”

Daniel died on September 10 after flying to the Bahamas where Anna Nicole, 38, had just given birth to a girl she has named Hannah Rose. (...)

Autopsy Shows Smiths Son on Medication
forbes.com 18.9.2006
Anna Nicole Smith's son was on prescription anti-depression medication when he died at the hospital bedside of the former reality TV star, a pathologist who did a second autopsy on 20-year-old Daniel Smith said Monday.

Forensic pathologist Cyril Wecht said Daniel Smith was being treated for depression that began about four to six weeks earlier, but he did not know whether the medication played any role in his death, which came three days after his celebrity mother gave birth in the Bahamas.

Wecht, speaking by phone from Miami a day after conducting the autopsy in the Bahamas, said he's still awaiting toxicology tests to determine the cause of death. (...)

FDA warns on migraine drugs, antidepressants taken together
marketwatch.com 19.7.2006
WASHINGTON (MarketWatch) -- The Food and Drug Administration said Wednesday patients and doctors need to be aware of the possibility that taking certain types of migraine drugs and antidepressants at the same time could cause a potentially life-threatening problem known as serotonin syndrome. (...)

Serotonin toxicity associated with the use of linezolid: a review of postmarketing data
Clin Infect Dis. 2006 Jun 1;42(11):1578-83
(...) CONCLUSION: The use of linezolid with medications that increase concentrations of serotonin in the central nervous system may result in serotonin toxicity. Prescribers must weigh risks and benefits of this combination. Patients and prescribers should be cognizant of signs and symptoms of serotonin toxicity and should initiate appropriate measures if such symptoms develop.

FIKK 2,2 MILL. etter ansiktskramper
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. (...)

Expert in addiction medicines testifying
abbynews.com 21.10.2006
The trial of James Swanney - the former Abbotsford doctor charged with criminal negligence causing the death of patient Christena Constible in 2000 - continued Tuesday with an expert in addiction medicines testifying about normal practices for prescribing methadone.

Dr. Garth McIver, who has been involved with methadone maintenance for approximately a decade, testified that the preferred method of giving methadone to patients is by way of a "direct, witnessed ingestion by a pharmacist." (...)

That prompted objections from defence lawyer Terry Robertson, who said Constible's cause of death did not involve Paxil. He argued it was irrelevant to the case that Swanney gave Constible Paxil and said it may be prejudicial to Swanney's case if the witness disagreed with Swanney's decision to give the drug to Constible. (...)

Legemidler mot migrene og antidepressiva kan være en farlig kombinasjon

Migraine Meds and Antidepressants Can Be a Dangerous Combination (Legemidler mot migrene og antidepressiva kan være en farlig kombinasjon)
about.com 30.10.2007
According to data presented at the annual congress of the European College of Neuropsychopharmacology and reported on by Elsevier Global Medical News, approximately 700,000 Americans were at risk for serotonin syndrome in 2004 because they were using a triptan for migraine headaches along with a selective serotonin reuptake inhibitor (SSRI) or serotonin-norepinephrine reuptake inhibitor (SNRI) for depression.

The figure of 700,000 was obtained from the most recent data from the annual U.S. National Ambulatory Medical Care Survey. Based upon this data, about 50.4 million Americans were prescribed either an SSRI or SNRI in 2004, almost 3.9 million patients were prescribed a triptan, and 694,276 individuals were on both at the same time.

“The potential for coadministration could be even greater now", says Linda M. Robison of the pharmacoeconomics and pharmacoepidemiology research unit at Washington State University, Pullman, "given how much the use of the SSRI and SNRI antidepressants has increased since 2004, along with the increase that’s occurred in the use of triptans for treatment of migraine headaches.”

Serotonin syndrome is a potentially life-threatening condition in which there is an excess of serotonin in the central nervous system. Among its symptoms are: mental confusion, hypomania, agitation, headache, coma, shivering, sweating, fever, hypertension, tachycardia, nausea, diarrhea, myoclonus/clonus, hyperreflexia and tremor. Patients experiencing any of these symptoms should seek medical assistance immediately.

The SSRIs include the drugs Celexa, Lexpro, Luvox, Paxil, Prozac and Zoloft. The SNRIs include Cymbalta, Effexor, Pristiq, Serzone and the diet drug Meridia. (...)

(Anm: Serotonin syndrom (SS), kramper, parkinsonisme osv.)

Øker hyperthyreose dødsrisiko ved inntak av Ecstasy?

Does Hyperthyroidism Increase Risk of Death Due to the Ingestion of Ecstasy? (Øker hyperthyreose dødsrisiko ved inntak av Ecstasy?)
J Forensic Sci. 2007 May 25; [Epub ahead of print]
Ecstasy (3,4-methylenedioxymethamphetamine, MDMA) is a psychoactive amphetamine derivative widely used for recreational purposes. Deaths caused by acute drug intoxication with MDMA are rare but can often involve a severe hyperthermic episode. The factors underlying the increased risk of some ecstasy users to a fatal drug reaction are not known. We present a case report of a 24-year-old woman who developed fatal hyperthermia with multi-organ complications following MDMA use and was found at autopsy to have diffuse thyroid hyperplasia (Graves' disease). An antemortem blood MDMA concentration of 0.68 mg/L was measured in a sample obtained on admission to hospital. Although a cause and effect cannot be established, as the thyroid hormone is a major regulator of thermogenesis, we suggest that hyperthyroidism predisposed the subject to ecstasy-induced hyperthermia and that a pre-existing defect affecting temperature status could be one factor in explaining some ecstasy intoxication deaths. (...)

Øker SSRI-preparater risiko for Parkinson og Alzheimers sykdom?

Depression May Be Early Sign of Parkinson's Disease
healthfinder.gov 27.4.2007
(...) Eksperter sa at leger altfor ofte legger skylden på humørsvingers innflytelse på diagnoser. (Too often, doctors may blame mood change on impact of diagnosis, experts say.)

Han bemerket at tilleggsdata, ikke inkludert i den publiserte studie, indikerte at nyere brukere av antidepressiva -- de som hadde brukt legemidler i mindre enn ett år -- hadde tredoblet risiko for å utvikle Parkinsons sykdom enn mennesker som ikke brukte antidepressiva. (He noted that additional data, not included in the published study, indicated that newer users of antidepressants -- those who had been on the drugs for less than one year -- had a threefold higher risk of developing Parkinson's than people who had never used antidepressants.)

(Anm: En såkalt depresjon forårsaker ikke parkinsonisme, men legemidlene (SSRI-er) kan beviselig forårsake bevegelighetsforstyrrelser (ekstrapyramidale symptomer), dvs. mulige hjerneskader (inklusive parkinsonisme etc.).

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

Nytt håp i Alzheimer-gåten?
mozon.no 2.2.2007
Dårlig motorikk kan være et tegn på svekket hukommelse hos eldre. Videre forskning kan vise om det har sammenheng med Alzheimers sykdom. (...)

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. (...)

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

- They describe these effects as a "nightmare" and like "torture"

Antidepressants Now No. 1 Drug Prescribed For Women 18-44
nbc4.com 16.11.2007
High Number Of Prescriptions Worrying Some Experts (...)

But not everyone is so lucky. In fact, about two-thirds of people on these drugs experience side effects, which can be severe and devastating.

Internet bloggers are even sharing their experiences with antidepressants online. They describe these effects as a "nightmare" and like "torture." Common reactions include "weight gain, decreased sex drive and severe stomach cramping."

"Something is going on with these drugs," Zuckerman said. "Not everybody metabolizes them the same way. It doesn't have the same effect on every person and some people are harmed by them."

Casalihno is now exercising to combat her depression. She says a pill wasn't the answer for her.

"I was overloaded with everything and I wasn't really addressing the root of the problems," Casalihno said. (...)

Mitochondrial Toxicity Associated with Linezolid

Serotonin Toxicity as a Consequence of Linezolid Use in Revision Hip Arthroplasty
ORTHOPEDICS 2008; 31:1140
Linezolid is the first in a new group of antibiotics called oxazolidinones. As a potent antimicrobial, it has activity against methicillin-resistant Staphylococcus aureus (MRSA), vancomycin-resistant Enterococcus, penicillin-resistant Streptococcus pneumoniae, and macrolide-resistant Streptococci.1 It was originally developed as an antidepressant because it has a weak reversible monoamine oxidase inhibitor effect. There is obvious potential for linezolid to cause serotonin toxicity due to the monoamine oxidase inhibitors properties; however, phase III trials reported no event of this nature.1 Since its release into the worldwide pharmaceutical market, there have been a number of documented case reports of serotonin toxicity2-7 when used in combination with selective serotonin reuptake inhibitors. Common examples of selective serotonin reuptake inhibitors include venlafaxine, citalopram, escitalopram, fluvoxamine, paroxetine, and sertraline. (...)

(Anm: MRSA; Forkortelsen MRSA står for meticillinresistente Staphylococcus aureus. Det vil si gule stafylokokker som er blitt resistente mot de typer antibiotika som oftest brukes mot stafylokokkinfeksjoner.)

Mitochondrial Toxicity Associated with Linezolid (Mitokondrisk giftighet assosiert med Linezolid)
NEJM 2005;353:2305-2306 (November 24)
To the Editor: Linezolid belongs to a family of antimicrobial agents (oxazolidinones) that inhibit bacterial protein synthesis by preventing the fusion of 30S and 50S ribosomal subunits.¹Hyperlactatemia, metabolic acidosis, and peripheral neuropathy are adverse effects of linezolid,²^,³ which could be related to the drug's capacity for interference with mitochondrial function.⁴We studied mitochondria from three patients in whom asthenia and hyperlactatemia developed during a prolonged course of oral linezolid (600 mg every 12 hours).

Patient 1, a 25-year-old man with Enterococcus faecium infection of a knee prosthesis, received oral linezolid. After three months, mild . . . [Full Text of this Article] (...)

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

Neuroleptisk malignt syndrom (Neuroleptic Malignant Syndrome (NMS)

Antidepressant labels to carry new warning of life-threatening side effect
latimesblogs.latimes.com 5.2.2009
The FDA has ordered a wide range of antidepressants to carry new warnings of an unusual but potentially deadly side effect seen most often in the first few weeks of treatment or when a patient increases dosages. The labels of two classes of new-generation medications for depression -- selective serotonin reuptake inhibitors (SSRIs) and serotonin-norepinephrine reuptake inhibitors (SNRIs) must now notify patients that malignant neuroleptic syndrome has been linked to the use of these drugs.

Among the drug companies ordered to revise their labels to alert patients of the danger were those making Celexa, Cymbalta, Effexor, Lexapro, Paxil, Pexeva, Pristiq, Prozac, Venlafaxine and Zoloft. The orders were dated Feb. 4, but disseminated this morning in a public notice of FDA actions.

In malignant neuroleptic syndrome, patients experience muscle rigidity, extreme variations in body temperature and wild fluctuations of heart rate and blood pressure -- all signs of malfunction in the body's autonomic nervous system, which regulates involuntary body functions. Malignant neuroleptic syndrome has been associated with older antipsychotic medication such as haloperidol, lithium salts and risperidone. But the widespread use of SSRI and SNRI antidepressants has made this syndrome a more common and visible affliction.
With one in 10 Americans taking prescription antidepressants, medicines such as Zoloft, Prozac and Effexor are currently the most commonly prescribed class of drugs in the United States, just ahead of high-blood pressure medicine, according to the Centers for Disease Control. And SSRIs and SNRIs have become by far the most common types of antidepressant dispensed by pharmacies, driving a tripling of prescriptions since 1988.

Malignant neuroleptic syndrome is a rare but extremely dangerous condition that results in death in, by some estimates, 10% to 20% of cases. Until recently, it was so uncommon it was unlikely to be recognized in many emergency departments. But the widespread use of SSRIs and SNRI antidepressants had made this bizarre syndrome a more common affliction seen in emergency departments.

A Food and Drug Administration spokeswoman said this afternoon that she had not been notified of the labeling change and was unaware of what led to it. Watch this space. (...)

(Anm: neuroleptisk malignt syndrom (Neuroleptic Malignant Syndrome (NMS)) alvorleg skadeverknad som kan koma ved bruk av haloperidol, fenotiazin, tioxantin eller andre middel mot sinnssjukdom eller ved seponering av dopaminantagonistar: vedhaldande muskelknyting ev muskelveikskap, for stor varmeproduksjon, vasokonstriksjon i huda, svekka medvett, rask puls og skiftande blodtrykk, dehydrering, uttrøytting, feber m v; kan føra til døden; årsak er visstnok hemming av dopaminerge system sentralt; kan likna sterkt på serotoninergt syndrom; EN neuroleptic malignant syndrome. Kilde: Norsk medisinsk ordbok.)

- Veteraner som tar PTSD-legemidler dør under søvn

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

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

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

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

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

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

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

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

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

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

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

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

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

- 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. (...)

For Some Troops, Powerful Drug Cocktails Have Deadly Results (For noen soldater, har kraftige cocktailer av legemidler dødelige resultater)
nytimes.com 18.2.2011
In his last months alive, Senior Airman Anthony Mena rarely left home without a backpack filled with medications.

He returned from his second deployment to Iraq complaining of back pain, insomnia, anxiety and nightmares. Doctors diagnosed post-traumatic stress disorder and prescribed powerful cocktails of psychiatric drugs and narcotics.

Yet his pain only deepened, as did his depression. “I have almost given up hope,” he told a doctor in 2008, medical records show. “I should have died in Iraq.”

Airman Mena died instead in his Albuquerque apartment, on July 21, 2009, five months after leaving the Air Force on a medical discharge. A toxicologist found eight prescription medications in his blood, including three antidepressants, a sedative, a sleeping pill and two potent painkillers.

Yet his death was no suicide, the medical examiner concluded. What killed Airman Mena was not an overdose of any one drug, but the interaction of many. He was 23.

After a decade of treating thousands of wounded troops, the military’s medical system is awash in prescription drugs — and the results have sometimes been deadly. (...)

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

- Graviditetsrelaterte hjerneslag øker

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

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

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

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

- Større risiko for tilbakefall hos pasienter som bruker antidepressiva

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

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

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

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

Diverse artikler

Antipsychotics leading to neuroleptic malignant syndrome in pregnancy
Obstet Gynecol. 2012 Feb;119(2 Pt 2):436-8.
BACKGROUND: Neuroleptic malignant syndrome (NMS) is characterized by a tetrad of mental status changes, extrapyramidal symptoms, hyperpyrexia, and autonomic instability and can develop after the use of antipsychotics.

CASE: A young, multiparous woman presented at 26 weeks of gestation with acute psychosis and was treated with haloperidol until she developed rigidity of her extremities and then was switched to risperidone. She subsequently developed mental status changes, rigidity, hyperthermia, and autonomic instability, leading to a diagnosis of NMS. Risperidone was discontinued and, owing to ongoing psychosis, olanzapine was initiated. Subsequently, her symptoms resolved.

CONCLUSION: Neuroleptic malignant syndrome may complicate the treatment of pregnant women using antipsychotics. Clinicians should take into account the risks of untreated psychosis when discontinuing the offending agent and consider initiating alternative pharmacotherapy. (...)

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

Health Agencies Update
Serotonin Syndrome Update
JAMA. 2011;306(24):2661
Physicians should be particularly wary of using linezolid or methylene blue in patients taking selective serotonin reuptake inhibitors (SSRIs) or serotonin norepinephrine reuptake inhibitors (SNRIs) because the interaction might trigger serotonin syndrome, warns the US Food and Drug Administration (FDA). Such a combination may lead to a toxic buildup of serotonin in the brain and cause confusion, hyperactivity, impaired memory, and other problems.

Use of linezolid and methylene blue have been linked to adverse events in patients concurrently taking psychiatric medications.

The FDA had warned in July that linezolid (an antibiotic) or methylene blue (a drug used to treat methemoglobinemia that is also used as a marker or dye in some diagnostic procedures) can interact with drugs affecting the serotonin system. Since then, the agency learned that SSRIs and SNRIs are the psychiatric drugs most likely to trigger serotonin syndrome. The agency said it is not yet clear whether other psychiatric medications with weaker effects on the serotonin system are as likely to trigger these adverse events when used with linezolid or methylene blue. (...)

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

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

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

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

At least one death has been reported.

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

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

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

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

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

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

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

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

(Anm

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