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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 Tx

Risk Factors: Sternbach’s Criteria4: at least 3 of: AMS, restlessness, myoclonus, hyperreflexia, Antipyretic therapy
- drug related (higher potency agents, higher total daily dose, rapid dose escalation, concomitant drugs) diaphoresis, shivering, tremor, diarrhea, in coordination - not recommended b/c inc body temp d/t
- patient related (older age, , endogenous/acquired defects in MAOI activity, poor SSRI metabolizers) excessive muscular activity not change in
Radomski et al3 revised the Dx criteria hypothalamic temp set point
Mechanisms1,2,3,4 Ex of central/peripheral 5HT receptors overstim thru meds/drugs of abuse AMS (altered agitation, confusion, delirium, hallucinations, hyperactivity,
↑5HT production Dietary: tyramine, L-tryptophan & 5-hydroxytryptophan as 5HT precursor mental status) hypervigilance, hypomania, & pressured speech, coma Mild/ Moderate Sx
↑5HT release Amphetamine & derivatives Neuromuscular hyperreflexia, inc muscle tone, restlessness, rhabdomyolysis, - most resolves w/in 24-72 hrs
- Methylenedioxymethamphetamine (MDMA, ecstasy) abnormalities rigidity, shivering, tremor; spontaneous/ inducible/ ocular clonus - supportive care, Rx D/C, & Benzodiazepines
Cocaine, Fenfluramine, Levodopa Autonomic diarrhea, mydriasis, fever, flushing, inc bowel sounds, resp rate
MAOI, DM hyperactivity & tearing; HTN or hypoTN Severe Sx
Meperidine, Mirtazapine, Reserpine - Typically occur after inc dose, overdose, or addition of serotonergic Rx. - sedation, paralyzation & intubation
inhib of 5HT Amphetamine & derivatives Mostly 6 hrs after ingestion. - recommend admin of 5HT antagonists
reuptake Bromopheniramine, Chorpheniramine, Dextromethorphan (DM) - Can occur up to 6 weeks after d/c of long-acting Rx (Fluoxetine) or MAOi [Evidence Level D: anecdotal]
Cocaine, Fentanyl, Meperidine (Demerol), Propoxyphene - Mild 5HT Syndrome: more subacute or even chronic presentation. Sx might Cyprohepatadine H1RA w/ antiCh &
Pentazocine (Talwin) be dismissed or not attributed to meds (Periactin4) anti5HT charac
SSRI, TCA, Venlafaxine, Bupropion 4-8mg po q8h
Sibutramine (Meridia) Serotonin Syndrome VS. Neuroleptic Malignant Syndrome up to 48 h SE: drowsiness
SJW (Hypericum perforatum) Sudden, w/in 24 hr after Onset Slower, w/in 7 d following intro of or 30mg x1dose
Tramadol (Ultram), Trazodone, Nefazodone intro of serotonergic agent neuroleptic agent Chlorpromazine 5HT1A & 5HT2 RA
inhib of 5HT MAOi: Agitation, diarrhea Sx Dysphagia, hypersalivation, (Thorazine4) neuroleptic w/
metabolism - Linezolid incontinence 12.5mg x1dose antiCH effects
- Isocarboxazid, Phenelzine, Tranylcypromine Dilated pupils, myoclonus, Signs Hyperthermia (>38C), akinesia, up to 1mg/kg po
- Selegiline, hyperreflexia extrapyramidal “lead pipe” rigidity, or IM; repeat if Sx SE: hypoTN,
- Pargylene rhabdomyolysis returns dystonic/NMS
SJW 23 deaths until 1999 Mortality 15-20%
Postsynaptic 5-HT, receptor agonists Other Recommendations
receptor Buspirone, Carbamazepine - IV electrolytes = maintain diuresis >50-100
stimulation Lyseric acid diethylamid (LSD), Ecstacy mL/h to avoid myoglobinuria. Esp in
Meperidine, Li, Triptans diaphoretic pts.
Metoclopramide (inc long half-life of Fluoxetine by 4-6 days) - BZD (Lora/diazepam) for anxiety. BB may
Dihydroergotamine (DHE 45) benefit to block 5HT1A receptors(Propranolol).
Altered Rx elim SSRI inhibit Tramadol metabolism via CYP2D6 - Ziprasidone = most powerful blocker w/
moderate EPS.
References - Resuscitation (cool off, mech ventilation,
1. Pharmacist’s Letter. 2006; Vol 22, Number 220905. 9/06. antiepileptics, antiHTN agents) in serious
2. Taylor JJ, Wilson JW, and Estes LL. Linezolid and serotonergic drug interactions: a retrospective survey. cases.
CID 2006; 43: 180-187. - Most pt completely resolves w/in 24 hr after
3. Birmes P, Coppin D, Schmitt L, and Lauque D. Serotonin syndrome: a brief review. JAMC 2003; 168(11): admit (esp taking Cyproheptadine or CPZ). Sx
1439-1442. (Canadian Medical Association Journal: www.jamc.ca)
persists longer in 40% of pts.
4. Tisdale JE and Miller DA. Drug-induced diseases: prevention, detection, and management. ASHP 2005;
- Neuromuscular blockers for sustained
433-437.ISBN 1-58528-086-0.
myoclonus or severe hyperthermia.

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