Qs Serotonin Syndrome

Quang Bui – May Contain Errors & Frustrating Abbrev. & Summative References – Page 1 of 1 – Serotonergic Syndrome – Filed As QS serotonin syndrome.doc – As of 04/2009

Serotonergic Syndrome: Pathophysiology

S/Sx

Risk Factors: Sternbach’s Criteria4: at least 3 of: AMS, restlessness, myoclonus, hyperreflexia, - drug related (higher potency agents, higher total daily dose, rapid dose escalation, concomitant drugs) diaphoresis, shivering, tremor, diarrhea, in coordination - patient related (older age, , endogenous/acquired defects in MAOI activity, poor SSRI metabolizers) Radomski et al3 revised the Dx criteria Mechanisms1,2,3,4 Ex of central/peripheral 5HT receptors overstim thru meds/drugs of abuse AMS (altered agitation, confusion, delirium, hallucinations, hyperactivity, mental status) hypervigilance, hypomania, & pressured speech, coma ↑5HT production Dietary: tyramine, L-tryptophan & 5-hydroxytryptophan as 5HT precursor Neuromuscular hyperreflexia, inc muscle tone, restlessness, rhabdomyolysis, ↑5HT release Amphetamine & derivatives abnormalities rigidity, shivering, tremor; spontaneous/ inducible/ ocular clonus - Methylenedioxymethamphetamine (MDMA, ecstasy) Cocaine, Fenfluramine, Levodopa Autonomic diarrhea, mydriasis, fever, flushing, inc bowel sounds, resp rate MAOI, DM hyperactivity & tearing; HTN or hypoTN Meperidine, Mirtazapine, Reserpine Typically occur after inc dose, overdose, or addition of serotonergic Rx. inhib of 5HT Amphetamine & derivatives Mostly 6 hrs after ingestion. reuptake Bromopheniramine, Chorpheniramine, Dextromethorphan (DM) Can occur up to 6 weeks after d/c of long-acting Rx (Fluoxetine) or MAOi Cocaine, Fentanyl, Meperidine (Demerol), Propoxyphene Mild 5HT Syndrome: more subacute or even chronic presentation. Sx might Pentazocine (Talwin) be dismissed or not attributed to meds SSRI, TCA, Venlafaxine, Bupropion Sibutramine (Meridia) Serotonin Syndrome VS. Neuroleptic Malignant Syndrome SJW (Hypericum perforatum) Sudden, w/in 24 hr after Onset Slower, w/in 7 d following intro of Tramadol (Ultram), Trazodone, Nefazodone intro of serotonergic agent neuroleptic agent inhib of 5HT MAOi: Agitation, diarrhea Sx Dysphagia, hypersalivation, metabolism Linezolid incontinence Isocarboxazid, Phenelzine, Tranylcypromine Dilated pupils, myoclonus, Signs Hyperthermia (>38C), akinesia, Selegiline, hyperreflexia extrapyramidal “lead pipe” rigidity, Pargylene rhabdomyolysis SJW 23 deaths until 1999 Mortality 15-20% Postsynaptic 5-HT, receptor agonists receptor Buspirone, Carbamazepine stimulation Lyseric acid diethylamid (LSD), Ecstacy Meperidine, Li, Triptans Metoclopramide (inc long half-life of Fluoxetine by 4-6 days) Dihydroergotamine (DHE 45) Altered Rx elim SSRI inhibit Tramadol metabolism via CYP2D6 References 1. Pharmacist’s Letter. 2006; Vol 22, Number 220905. 9/06. 2. Taylor JJ, Wilson JW, and Estes LL. Linezolid and serotonergic drug interactions: a retrospective survey. CID 2006; 43: 180-187. 3. Birmes P, Coppin D, Schmitt L, and Lauque D. Serotonin syndrome: a brief review. JAMC 2003; 168(11): 1439-1442. (Canadian Medical Association Journal: www.jamc.ca) 4. Tisdale JE and Miller DA. Drug-induced diseases: prevention, detection, and management. ASHP 2005; 433-437.ISBN 1-58528-086-0.

Tx Antipyretic therapy - not recommended b/c inc body temp d/t excessive muscular activity not change in hypothalamic temp set point Mild/ Moderate Sx - most resolves w/in 24-72 hrs - supportive care, Rx D/C, & Benzodiazepines Severe Sx - sedation, paralyzation & intubation - recommend admin of 5HT antagonists [Evidence Level D: anecdotal] Cyprohepatadine H1RA w/ antiCh & (Periactin4) anti5HT charac 4-8mg po q8h up to 48 h SE: drowsiness or 30mg x1dose Chlorpromazine 5HT1A & 5HT2 RA (Thorazine4) neuroleptic w/ 12.5mg x1dose antiCH effects up to 1mg/kg po or IM; repeat if Sx SE: hypoTN, returns dystonic/NMS Other Recommendations - IV electrolytes = maintain diuresis >50-100 mL/h to avoid myoglobinuria. Esp in diaphoretic pts. - BZD (Lora/diazepam) for anxiety. BB may benefit to block 5HT1A receptors(Propranolol). - Ziprasidone = most powerful blocker w/ moderate EPS. - Resuscitation (cool off, mech ventilation, antiepileptics, antiHTN agents) in serious cases. - Most pt completely resolves w/in 24 hr after admit (esp taking Cyproheptadine or CPZ). Sx persists longer in 40% of pts. - Neuromuscular blockers for sustained myoclonus or severe hyperthermia.