Serotonin syndrome
Background
- Can be produced by any serotonergic medication
- 1 in 6 U.S. adults take at least one psychoactive medication[1]
- Majority of cases occur within therapeutic drug dosages
- Most common cause is ingestion of foods high in L-Tryptophan while taking an MAOI. Second most common is ingestion of both SSRI and MAOI[2]
- Most common cause of death is severe hyperthermia
Causative Agents[3]
Antidepressants
- SSRIs
- SNRIs
- Bupropion[4]
- Buspirone
- TCAs
- Lithium
- Mirtazapine
- Trazodone
- Valproic acid
- MAOIs (should have washout period of 2+ weeks prior to starting a SSRI)
- Phenelzine
- Selegiline
- Tranylcypromine
Drugs of Abuse
Analgesics
- Fentanyl
- Meperidine (Demerol)
- Methadone
- Tramadol
Antiemetics
Over the counter Medications
- Dextromethorphan
- Oral decongestants (Pseudoephedrine)
Herbal products
- St John’s Wort, Ginseng, Nutmeg, Yohimbe
Other Medications
- Triptans
- Ergot alkaloids
- Bromocriptine
- Linezolid
- Carbamazepine
- Cyclobenzaprine
- L-tryptophan, 5-hydroxytryptophan
- Methylene blue
Clinical Features
- Altered mental status: Agitated delirium. Patients generally hyperactive.
- Autonomic Instability: Hyperthermia, tachycardia, hypertension, diaphoresis, gastrointestinal illness [5]
- Often labile blood pressure, HR
- Neuromuscular Abnormalities: Clonus, ocular clonus, myoclonus, rigidity, hyperreflexia, tremor, seizures
- More pronounced in the lower extremities
- Clonus (inducible or spontaneous): most common finding[6]
- Important to identify because it does not occur in other conditions that mimic serotonin syndrome
- Hyperactivity as opposed to rigidity in neuroleptic malignant syndrome
Differential Diagnosis
Movement Disorders and Other Abnormal Contractions
- Chorea
- Neuroleptic malignant syndrome
- Serotonin syndrome
- Hypocalcemia
- Strychnine toxicity
- Acute tetanus
- Parkinson's disease
- Mono amine oxidase inhibitor toxicity
- Phencyclidine toxicity
- Anti-NMDA receptor encephalitis
- Huntington disease
- Wilson's disease
- CVA
- Schizophrenia
- Psychotic agitation
- Dementia
- Lewy body dementia
- Vascular dementia
- Frontotemporal dementia
- Dystonic reaction
- Extrapyramidal reaction
- Torticollis
- Idiopathic movement disorder
Altered mental status and fever
- Infectious
- Sepsis
- Meningitis
- Encephalitis
- Cerebral malaria
- Brain abscess
- Other
Evaluation
Hunter Toxicity Criteria Decision Rules
Serotonergic agent plus 1 of the following[7]:
- Spontaneous clonus
- Inducible clonus AND (agitation or diaphoresis)
- Ocular Clonus AND (agitation or diaphoresis)
- Tremor AND hyperreflexia
- Hypertonia AND temperature >38 AND (ocular clonus or inducible clonus)
84% Sn, 97% Sp
Serotonin syndrome vs Neuroleptic malignant syndrome
- History of a new serotonergic drug or a dose increase of a serotonergic drug are helpful
- Serotonin syndrome is usually much more acute in onset than NMS which may develop over days or weeks
- Presence of ‘lead pipe’ rigidity is typical of NMS, while serotonin syndrome typically manifests with tremor and hyperreflexia
- Elevations in CK, LFTs, and WBC, coupled with a low iron level, distinguishes NMS from serotonin syndrome among patients taking both neuroleptic and serotonin agonist medications simultaneously
Management
- Discontinue all serotonergic drugs
- Aggressive supportive care
- If pressors required, direct acting (e.g. norepinephrine, epi) preferred, MAO inhibition causes erratic response to dopamine
- Benzos
- Goal is to eliminate agitation, neuromuscular abnormalities, elevations in HR/BP
- In severe cases, large doses are required (diazepam IV 10-20 mg, titrated with 10 mg increments)
- Cyproheptadine[8]
- Give if benzodiazepines and supportive care fail to improve agitation and abnormal vitals
- Serotonin antagonist
- Also has antihistamine and anticholinergic properties that may exacerbate other mixed toxicology picture
- Give 12mg PO/NG; repeat with 2mg q2hr until clinical response is seen (max 32mg/d)
- Give 4mg q6hr x48hr if patient is responsive to initial dose
- Chlorpromazine[9]
- Phenothiazine with antiserotonergic effects
- 50mg to 100mg IM
- Avoid in:
- Hemodynamically unstable patients as can cause serious hypotension[10]
- Cases in which NMS may still be on the differential
- Dexmedetomidine[11][12]
- Small case series found this helpful in adolescent cases refractory to benzos
- Dantrolene generally not recommended as it can worsen serotonin toxicity[13]
- Treat hyperthermia
- Hyperthermia due to increase in muscular activity, not change in set point
- Intubate and paralyze if temperature > 41.1
- Standard cooling measures
- Fans, water sprays, ice packs, cooled crystalloids, cooling blankets
Disposition
- Severe cases may require intubation and ventilation in ICU
- 24hr admission for altered mental status or abnormal vital signs requiring further supportive care
- Discharge mild cases with minimal intervention required after 6 hrs of observation
See Also
References
- ↑ Moore TJ and Mattison DR. Adult Utilization of Psychiatric Drugs and Differences by Sex, Age, and Race. JAMA Intern Med. Published online December 12, 2016. doi:10.1001/jamainternmed.2016.7507.
- ↑ Stork CM. Serotonin Reuptake Inhibitors and Atypical Antidepressants. In: Flomenbaum N, Goldfrank L, Hoffman R, Howland MA, et al, eds. Goldfrank’s Toxicologic Emergencies. 8th Ed. New York, NY: McGraw-Hill; 2006: 1070-1082
- ↑ Brown CH. Drug-induced Serotonin Syndrome. US Pharm. 2010;35(11):HS-16-HS-21.
- ↑ Thorpe EL, Pizon AF, Lynch MJ, Boyer J. Bupropion induced serotonin syndrome: a case report. J Med Toxicol. 2010;6(2):168-171. doi:10.1007/s13181-010-0021-x
- ↑ Boyer, E. W. and Shannon, M. (2005) ‘The Serotonin Syndrome’, New England Journal of Medicine, 352(11), pp. 1112–1120. doi: 10.1056/nejmra041867
- ↑ Farkas, J. Serotonin Syndrome. The Internet Book of Critical Care. https://emcrit.org/ibcc/serotonin/. Published June 13th, 2019. Accessed December 31st, 2020.
- ↑ Dunkley EJ, Isbister GK, Sibbritt D, Dawson AH, Whyte IM. The Hunter Serotonin Toxicity Criteria: simple and accurate diagnostic decision rules for serotonin toxicity. QJM 2003;96:635-642
- ↑ Graudins, A., Stearman, A. and Chan, B. (1998) ‘Treatment of the serotonin syndrome with cyproheptadine’, The Journal of Emergency Medicine, 16(4), pp. 615–619. doi: 10.1016/s0736-4679(98)00057-2
- ↑ Gillman PK. The serotonin syndrome and its treatment. J Psychopharmacol 1999;13:100-109
- ↑ Frank C. Recognition and treatment of serotonin syndrome. Can Fam Physician. 2008 Jul; 54(7): 988–992.
- ↑ Rushton WF, Charlton NP. Dexmedetomidine in the treatment of serotonin syndrome. Ann Pharmacother. 2014; 48(12):1651-1654.
- ↑ Duggal HS, Fetchko J. Serotonin syndrome and atypical antipsychotics. Am J Psychiatry. 2002;159(4):672–3.
- ↑ Boyer EW, Shannon M. The serotonin syndrome. N Engl J Med. 2005 Mar 17; 352(11):1112-20.