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Selective Serotonin Reuptake Inhibitor Toxicity Medication

  • Author: Tracy A Cushing, MD, MPH, FACEP, FAWM; Chief Editor: Asim Tarabar, MD  more...
 
Updated: Oct 21, 2015
 

Medication Summary

Pharmacologic treatment of serotonin syndrome (SS) is largely based on anecdotal case reports and on animal models. Supportive care remains the basis of treatment; however, severe cases may benefit from the following interventions:

  • Adsorbent antidotes - Activated charcoal
  • Serotonin antagonists - Cyproheptadine
  • Sedatives and anticonvulsants - Lorazepam, diazepam, midazolam
  • Antihypertensives - Nitroprusside, esmolol
  • Paralytic neuromuscular blockade - Rocuronium, vecuronium
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Antidotes, Other

Class Summary

These agents inhibit gastrointestinal absorption of certain toxic agents or irritants. Cyproheptadine, chlorpromazine, and risperidone have been reported to possibly be useful in serotonin syndrome (SS) through blockage of postsynaptic serotonin receptors. No formalized dosing regimens have been established; the following recommendations are based on case reports and reviews of serotonin toxicity treatment.

Activated charcoal (Actidose-Aqua, Actidose with Sorbitol, EZ-Char, Requa Activated Charcoal)

 

Activated charcoal is used as an emergency treatment for poisoning caused by drugs and chemicals, preventing absorption of a drug by adsorbing the drug in the intestine. The network of pores present in activated charcoal absorbs 100-1000 mg of drug per gram of charcoal. Multidose charcoal may interrupt enterohepatic recirculation and enhance elimination by enterocapillary exsorption.

Theoretically, by constantly bathing the gastrointestinal tract with charcoal, the intestinal lumen serves as a dialysis membrane for reverse absorption of drug from intestinal villous capillary blood into the intestine. Activated charcoal does not dissolve in water.

For maximum effect, administer charcoal (1g/kg) within 30-60 minutes after poison ingestion. The addition of sorbitol results in hyperosmotic laxative action, which causes catharsis, further inhibiting intestinal absorption of toxic substances.

Cyproheptadine

 

Cyproheptadine is a first-generation H1-receptor antagonist in blood vessels, the gastrointestinal tract, and the respiratory tract, with some anticholinergic and antiserotoninergic properties. It has been shown in animal studies and case reports to reduce symptoms of SS.[25] It may be helpful in mild-to=moderate cases of SS.

Chlorpromazine (Thorazine)

 

Chlorpromazine is a dopamine antagonist developed initially as a typical antipsychotic, but it also has some antiserotonergic properties. Case reports have described chlorpromazine improving the symptoms of SS.[26]

Following charcoal administration, chlorpromazine is a better choice in treating toxicity because it can be administered intravenously while cyproheptadine is not available in an intravenous form. However, it is best to avoid chlorpromazine if the drugs inducing serotonin toxicity have significant cardiogenic or epileptogenic properties.

Risperidone (Risperdal)

 

Risperidone is a 5-HT2a antagonist, used mainly as an atypical antipsychotic in the treatment of schizophrenia because of its antidopaminergic properties. In animal models, risperidone has been shown to completely inhibit the onset of symptoms of SS. Other potent 5-HT2a antagonists, such as ritanserin and pipamperone, have been shown to prevent the onset of SS when given in prophylactic doses. However, medications with specific 5-HT1a antagonism, such as propranolol, have not been shown to prevent SS, suggesting that perhaps the 5-HT2a receptor is the more important receptor implicated in the pathophysiology of SS.[27, 28]

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Anxiolytics, Benzodiazepines

Class Summary

Benzodiazepines are considered a mainstay of serotonin syndrome (SS) treatment, particularly as a therapy for neuromuscular symptoms and seizures. They are also excellent for controlling agitated behavior.

Lorazepam (Ativan)

 

Lorazepam is a sedative with rapid onset and a relatively long half-life. By increasing the action of gamma-aminobutyric acid (GABA), which is a major inhibitory neurotransmitter in the brain, it may depress all levels of the central nervous system (CNS), including the limbic and reticular formation. Lorazepam's anticonvulsant effects last longer than those of diazepam or midazolam (4-6 h).

Diazepam (Valium, Diastat)

 

Diazepam modulates postsynaptic effects of GABA-A transmission, resulting in an increase in presynaptic inhibition. It appears to act on part of the limbic system, thalamus, and hypothalamus to induce a calming effect. Diazepam has also been found to be an effective adjunct for the relief of skeletal muscle spasm caused by upper motor neuron disorders.

Diazepam rapidly distributes to other body fat stores. Twenty minutes after the drug's initial IV infusion, diazepam's serum concentration drops to 20% of maximum concentration. Individualize the dosage and increase it cautiously to avoid adverse effects.

Clonazepam (Klonopin)

 

Clonazepam is a benzodiazepine with anticonvulsant properties that may be useful in the setting of myoclonus.

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Vasodilators

Class Summary

Antihypertensives are used for the treatment of autonomic instability and malignant hypertension as evidenced by end-organ damage to the brain, heart, and/or kidneys.

Nitroprusside (Nitropress)

 

Nitroprusside produces arterial and venous vasodilation. It decreases afterload and preload and may produce a reflex tachycardia.

Esmolol (Brevibloc)

 

Esmolol is a cardioselective beta- 1-receptor blocker with a short duration of action that decreases both afterload and cardiac output in the setting of tachycardia/hypertension, and it is easily titratable.

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Neuromuscular Blockers, Depolarizing

Class Summary

To control hyperreflexia, clonus, and hyperthermia, total neuromuscular paralysis may be required. Succinylcholine should be avoided in serotonin syndrome (SS), given the risk of hyperkalemia secondary to rhabdomyolysis.

Rocuronium (Zemuron)

 

Rocuronium is a nondepolarizing neuromuscular blocking agent with rapid to intermediate onset (depending on dose) and intermediate duration. It competes for cholinergic receptors at the motor end-plate to antagonize the action of acetylcholine, which in turn blocks neuromuscular transmission. Acetylcholinesterase inhibitors such as neostigmine and edrophonium antagonize action.

Vecuronium

 

Vecuronium is a prototypic, nondepolarizing neuromuscular blocking agent that reliably results in muscular paralysis. For intubation and maintenance of paralysis, a continuous infusion may be used.

Infants are more sensitive to neuromuscular blockade activity and, although the same dose is used, recovery is prolonged by 50%. Vecuronium is not recommended for use in neonates.

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Contributor Information and Disclosures
Author

Tracy A Cushing, MD, MPH, FACEP, FAWM Assistant Professor and Attending Physician, Department of Emergency Medicine, University of Colorado School of Medicine

Tracy A Cushing, MD, MPH, FACEP, FAWM is a member of the following medical societies: American College of Emergency Physicians, Society for Academic Emergency Medicine, Wilderness Medical Society

Disclosure: Nothing to disclose.

Coauthor(s)

Theodore I Benzer, MD, PhD Assistant Professor in Medicine, Harvard Medical School; Director of the ED Observation Unit, Director of Toxicology, Chair of Quality and Safety, Department of Emergency Medicine, Massachusetts General Hospital

Theodore I Benzer, MD, PhD is a member of the following medical societies: Alpha Omega Alpha, American College of Emergency Physicians

Disclosure: Nothing to disclose.

Monica Noori, MD Resident Physician, Department of Emergency Medicine, Denver Health

Monica Noori, MD is a member of the following medical societies: American College of Emergency Physicians, American Medical Association, Emergency Medicine Residents' Association

Disclosure: Nothing to disclose.

Chief Editor

Asim Tarabar, MD Assistant Professor, Director, Medical Toxicology, Department of Emergency Medicine, Yale University School of Medicine; Consulting Staff, Department of Emergency Medicine, Yale-New Haven Hospital

Disclosure: Nothing to disclose.

Additional Contributors

Howard Kim, MD Resident Physician, Department of Emergency Medicine, Denver Health Medical Center

Disclosure: Nothing to disclose.

Acknowledgements

John G Benitez, MD, MPH Associate Professor, Department of Medicine, Medical Toxicology, Vanderbilt University Medical Center; Managing Director, Tennessee Poison Center

John G Benitez, MD, MPH is a member of the following medical societies: American Academy of Clinical Toxicology, American Academy of Emergency Medicine, American College of Medical Toxicology, American College of Preventive Medicine, Society for Academic Emergency Medicine, Undersea and Hyperbaric Medical Society, and Wilderness Medical Society

Disclosure: Nothing to disclose.

Miguel C Fernandez, MD, FAAEM, FACEP, FACMT, FACCT Associate Clinical Professor, Department of Surgery/Emergency Medicine and Toxicology, University of Texas School of Medicine at San Antonio; Medical and Managing Director, South Texas Poison Center

Miguel C Fernandez, MD, FAAEM, FACEP, FACMT, FACCT is a member of the following medical societies: American Academy of Emergency Medicine, American College of Clinical Toxicologists, American College of Emergency Physicians, American College of Medical Toxicology, American College of Occupational and Environmental Medicine, Society for Academic Emergency Medicine, and Texas Medical Association

Disclosure: Nothing to disclose.

Francisco Talavera, PharmD, PhD Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Medscape Salary Employment

References
  1. Sternbach H. The serotonin syndrome. Am J Psychiatry. 1991 Jun. 148(6):705-13. [Medline].

  2. Boyer EW, Shannon M. The serotonin syndrome. N Engl J Med. 2005 Mar 17. 352(11):1112-20. [Medline].

  3. Olfson M, Marcus SC, Druss B, Elinson L, Tanielian T, Pincus HA. National trends in the outpatient treatment of depression. JAMA. 2002 Jan 9. 287(2):203-9. [Medline].

  4. Pirraglia PA, Stafford RS, Singer DE. Trends in Prescribing of Selective Serotonin Reuptake Inhibitors and Other Newer Antidepressant Agents in Adult Primary Care. Prim Care Companion J Clin Psychiatry. 2003 Aug. 5(4):153-157. [Medline]. [Full Text].

  5. Lawrence KR, Adra M, Gillman PK. Serotonin toxicity associated with the use of linezolid: a review of postmarketing data. Clin Infect Dis. 2006 Jun 1. 42(11):1578-83. [Medline].

  6. Kaplan H, Sadock B. Serotonin-specific reuptake inhibitors. Synopsis of Psychiatry. 8th ed. Williams and Wilkins; 1988. 1083-92.

  7. Hirsch M, Birnbaum R. Pharmacology of Antidepressants. UpToDate [serial online]. 2004. v 11.3.:

  8. Lane R, Baldwin D. Selective serotonin reuptake inhibitor-induced serotonin syndrome: review. J Clin Psychopharmacol. 1997 Jun. 17(3):208-21. [Medline].

  9. Flanagan RJ. Fatal toxicity of drugs used in psychiatry. Hum Psychopharmacol. 2008 Jan. 23 Suppl 1:43-51. [Medline].

  10. Gillman PK. The serotonin syndrome and its treatment. J Psychopharmacol. 1999. 13(1):100-9. [Medline].

  11. Birmes P, Coppin D, Schmitt L, Lauque D. Serotonin syndrome: a brief review. CMAJ. 2003 May 27. 168(11):1439-42. [Medline].

  12. Ener RA, Meglathery SB, Van Decker WA, Gallagher RM. Serotonin syndrome and other serotonergic disorders. Pain Med. 2003 Mar. 4(1):63-74. [Medline].

  13. Mason PJ, Morris VA, Balcezak TJ. Serotonin syndrome. Presentation of 2 cases and review of the literature. Medicine (Baltimore). 2000 Jul. 79(4):201-9. [Medline].

  14. White N, Litovitz T, Clancy C. Suicidal antidepressant overdoses: a comparative analysis by antidepressant type. J Med Toxicol. 2008 Dec. 4(4):238-50. [Medline]. [Full Text].

  15. Klein-Schwartz W, Benson BE, Lee SC, Litovitz T. Comparison of citalopram and other selective serotonin reuptake inhibitor ingestions in children. Clin Toxicol (Phila). 2012 Jun. 50(5):418-23. [Medline].

  16. Isbister GK, Bowe SJ, Dawson A, Whyte IM. Relative toxicity of selective serotonin reuptake inhibitors (SSRIs) in overdose. J Toxicol Clin Toxicol. 2004. 42(3):277-85. [Medline].

  17. US Food and Drug Administration. Celexa (citalopram hydrobromide): Drug Safety Communication – Abnormal Heart Rhythms Associated With High Doses. Available at http://www.fda.gov/Safety/MedWatch/SafetyInformation/SafetyAlertsforHumanMedicalProducts/ucm269481.htm. Accessed: August 24, 2011.

  18. Celexa (citalopram hydrobromide) [package insert]. St. Louis, Missouri: Forest Pharmaceuticals, Inc. August, 2011. Available at [Full Text].

  19. Targownik LE, Bolton JM, Metge CJ, Leung S, Sareen J. Selective serotonin reuptake inhibitors are associated with a modest increase in the risk of upper gastrointestinal bleeding. Am J Gastroenterol. 2009 Jun. 104(6):1475-82. [Medline].

  20. Mowry JB, Spyker DA, Cantilena LR Jr, McMillan N, Ford M. 2013 Annual Report of the American Association of Poison Control Centers' National Poison Data System (NPDS): 31st Annual Report. Clin Toxicol (Phila). 2014 Dec. 52 (10):1032-283. [Medline].

  21. 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 Sep. 96(9):635-42. [Medline].

  22. Chechani V. Serotonin syndrome presenting as hypotonic coma and apnea: potentially fatal complications of selective serotonin receptor inhibitor therapy. Crit Care Med. 2002 Feb. 30(2):473-6. [Medline].

  23. [Guideline] Nelson LS, Erdman AR, Booze LL, Cobaugh DJ, Chyka PA, Woolf AD, et al. Selective serotonin reuptake inhibitor poisoning: An evidence-based consensus guideline for out-of-hospital management. Clin Toxicol (Phila). 2007 May. 45(4):315-32. [Medline].

  24. Evans CE, Sebastian J. Serotonin syndrome. Emerg Med J. 2007 Apr. 24(4):e20. [Medline]. [Full Text].

  25. Graudins A, Stearman A, Chan B. Treatment of the serotonin syndrome with cyproheptadine. J Emerg Med. 1998 Jul-Aug. 16(4):615-9. [Medline].

  26. Gillman PK. The serotonin syndrome and its treatment. J Psychopharmacol. 1999. 13(1):100-9. [Medline].

  27. Nisijima K, Yoshino T, Yui K, Katoh S. Potent serotonin (5-HT)(2A) receptor antagonists completely prevent the development of hyperthermia in an animal model of the 5-HT syndrome. Brain Res. 2001 Jan 26. 890(1):23-31. [Medline].

  28. Nisijima K, Yoshino T, Ishiguro T. Risperidone counteracts lethality in an animal model of the serotonin syndrome. Psychopharmacology (Berl). 2000 May. 150(1):9-14. [Medline].

  29. Marx J, Hockberger R, Walls R. Rosen's Emergency Medicine. 5th ed. CV Mosby; 2002. 2087-2103.

 
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