Serotonin Syndrome ================== See Also: Malignant Hyperthermia vs. Neuroleptic Malignant Syndrome Can be caused by triptans for migraines alone: [Soldin, O. P., J. M. Tonning, et al. (2008). "Serotonin Syndrome Associated with Triptan Monotherapy." N Engl J Med 358(20): 2185-2186.] þ Cyproheptadine (e.g., Periactin): - dose 4 mg PO, may repeat x4 (though some argue for 20-30 mg) [Gillman PK. The serotonin syndrome and its treatment. J Psychopharmacol 1999; 13:100-9. Serotonin syndrome is caused by drug induced excess of intrasynaptic 5- hydroxytryptamine. The clinical manifestations are mediated by the action of 5-hydroxytryptamine on various subtypes of serotonin receptors. There is no effective drug treatment established. The history of the treatment of serotonin syndrome with 5-hydroxytryptamine blocking drugs is reviewed. A literature search was undertaken using both Medline and a manual search of the older literature. Reports of cases treated with the 5-HT2 blockers cyproheptadine and chlorpromazine were identified and analysed. There is some evidence suggesting the efficacy of chlorpromazine and cyproheptadine in the treatment of serotonin syndrome. The evidence for cyproheptadine is less substantial, perhaps because the dose of cyproheptadine necessary to ensure blockade of brain 5-HT2 receptors is 20-30 mg, which is higher than that used in the cases reported to date (4-16 mg).] - atypical antihistamine with anti-serotonin effects - recent case reports of efficacy [Mullins ME, Horowitz BZ. Serotonin syndrome after a single dose of fluvoxamine [letter; comment]. Ann Emerg Med 1999; 34:806-7.] [Horowitz BZ, Mullins ME. Cyproheptadine for serotonin syndrome in an accidental pediatric sertraline ingestion. Pediatr Emerg Care 1999; 15:325-7.] [Lappin RI, Auchincloss EL. Treatment of the serotonin syndrome with cyproheptadine [letter]. N Engl J Med 1994; 331:1021-2.] [Chan BS, Graudins A, Whyte IM, Dawson AH, Braitberg G, Duggin GG. Serotonin syndrome resulting from drug interactions. Med J Aust 1998; 169:523-5.] [Graudins A, Stearman A, Chan B. Treatment of the serotonin syndrome with cyproheptadine. J Emerg Med 1998; 16:615-9.] þ Differentiating from NMS: - SS has +++ reflexes, NMS not - SS is rapid, NMS develops over 3-9 days - SS is associated with serotonergics and NSM with neuroleptics - SS rigidity is mild, while NMS has "lead-pipe" rigidity - SS has clonus and nystagmus, NMS does not þ Symptoms of Serotonin Syndrome: - Altered Mental Status: akathisia, agitation, confusion, incoordination, mania, coma. - Autonomic instabiity: hyperthermia, tachypnea, diarrhea, mydriasis, diaphoresis, shivering, tachycardia, variable BP - Neuromuscular abnormalities: nystagmus, myoclonus, rigidity, tremor, hyperreflexia, clonus, seizures. þ Serotonin Syndrome caused by: - excess serotonin in CNS, - decreased reuptake - blocked metabolism, - upregulated receptors þ Specific initiators - excess or OD of SSRI (selective serotonin reuptake inhibitors) or SNRI (Serotonin-Norepinephrine Reuptake Inhibitors) or "Novel Antidepressnts" - can be caused by a single OD of an SSRI: [Gill M, LoVecchio F, Selden B. Serotonin syndrome in a child after a single dose of fluvoxamine [see comments]. Ann Emerg Med 1999; 33:457-9. Serotonin syndrome, a potentially fatal iatrogenic complication of psychopharmacologic therapy, is most commonly reported with combinations of serotonergic medications. Serotonin syndrome is characterized by alterations in cognition, behavior, autonomic, and central nervous system function as a result of increased postsynaptic serotonin receptor agonism. We present the first reported case of serotonin syndrome after a single dose of fluvoxamine in a pediatric patient after ingestion of a single supratherapeutic dose of fluvoxamine.] - Drug Interactions: + MOA inhibitor (Selegiline (Deprenyl) is supposed to be selective MAO-B inhibitor) + SSRI + SRI (Clomipramine, imipramine, TCAs, DM, Demerol, Talwin) (Ref: Tintinalli 4th ed. p 749, Rosen 3rd ed. p 2625) + herbal medicines including St. Johnswort [Med Ltr 2000;42(1081):56] + Agonists such as tryptophan, buspirone, lithium + N.B.: lithium upregulates 5-HT receptors [Ohman R, Spigset O. Serotonin syndrome induced by fluvoxamine-lithium interaction [letter]. Pharmacopsychiatry 1993; 26:263-4.] [Mekler G, Woggon B. A case of serotonin syndrome caused by venlafaxine and lithium. Pharmacopsychiatry 1997; 30:272-3.] [Sobanski T, Bagli M, Laux G, Rao ML. Serotonin syndrome after lithium add-on medication to paroxetine. Pharmacopsychiatry 1997; 30:106-7.] + cocaine + antibiotics such as Rifampin [Markowitz JS, DeVane CL. Rifampin-induced selective serotonin reuptake inhibitor withdrawal syndrome in a patient treated with sertraline [letter]. J Clin Psychopharmacol 2000; 20:109-10.] + tramadol [Kesavan S, Sobala GM. Serotonin syndrome with fluoxetine plus tramadol. J R Soc Med 1999; 92:474-5.] [Lantz MS, Buchalter EN, Giambanco V. Serotonin syndrome following the administration of tramadol with paroxetine [letter]. Int J Geriatr Psychiatry 1998; 13:343-5.] [Egberts AC, ter Borgh J, Brodie-Meijer CC. Serotonin syndrome attributed to tramadol addition to paroxetine therapy. Int Clin Psychopharmacol 1997; 12:181-2.] [Reeves RR, Bullen JA. Serotonin syndrome produced by paroxetine and low-dose trazodone [letter]. Psychosomatics 1995; 36:159-60.] + erythromycin [Lee DO, Lee CD. Serotonin syndrome in a child associated with erythromycin and sertraline. Pharmacotherapy 1999; 19:894-6.] + Demerol (meperidine) [Weiner AL. Meperidine as a potential cause of serotonin syndrome in the emergency department. Acad Emerg Med 1999; 6:156-8.] + MDMA (ecstasy) [Mueller PD, Korey WS. Death by "ecstasy": the serotonin syndrome? Ann Emerg Med 1998; 32:377-80.] + sumatriptan and other migraine treatments [Mathew NT, Tietjen GE, Lucker C. Serotonin syndrome complicating migraine pharmacotherapy. Cephalalgia 1996; 16:323-7.] + trazodone [Goldberg RJ, Huk M. Serotonin syndrome from trazodone and buspirone [letter]. Psychosomatics 1992; 33:235-6.] þ Serotonin Syndrome Scale: [Hegerl U, Bottlender R, Gallinat J, Kuss HJ, Ackenheil M, Moller HJ. The serotonin syndrome scale: first results on validity. Eur Arch Psychiatry Clin Neurosci 1998; 248:96-103.] þ SS morbidity: - hyperthermia and rigidity may lead to rhabdomyolysis þ Differential Diagnoses: - various ODs, including PCP. þ Rx - Agressive cooling - paralytics - Dantrolene - Benzodiazepines - questionable approaches: + dopamine antagonists: + methysergide + propanolol + chlorpromazine Spirko BA, Wiley JF, 2nd. Serotonin syndrome: a new pediatric intoxication. Pediatr Emerg Care 1999; 15:440-3. þ Serotonin Syndrome may be same as neuroleptic malignant syndrome - NMS: + long term neuroleptics + withdrawal of dopamine agonists + rigidity rather than myoclonus - ? if central hyperthermic hyperexcitability syndrome found in both SS and NMS