The serotonin syndrome



	Full Text (PDF)
	Alert me when this article is cited
	Alert me if a correction is posted
	Citation Map



	Email this article to a Colleague
	Similar articles in this journal
	Similar articles in PubMed
	Alert me to new issues of the journal
	Add to My Articles & Searches
	Download to citation manager



	Citing Articles via HighWire
	Citing Articles via Google Scholar



	Articles by Sternbach, H.
	Search for Related Content



	PubMed Citation
	Articles by Sternbach, H.

Am J Psychiatry 1991; 148:705-713
Copyright © 1991 by American Psychiatric Association

SPECIAL ARTICLES

The serotonin syndrome

H Sternbach
Department of Psychiatry, UCLA-Neuropsychiatric Institute, Los Angeles.

OBJECTIVE AND METHOD: A review of the literature on the serotonin syndrome in animals and human beings was conducted, and 12 reports of 38 cases in human patients were then analyzed to determine the most frequently reported clinical features and drug interactions, as well as the incidence, treatment, and outcome of this syndrome. FINDINGS: The serotonin syndrome is most commonly the result of the interaction between serotonergic agents and monoamine oxidase inhibitors. The most frequent clinical features are changes in mental status, restlessness, myoclonus, hyperreflexia, diaphoresis, shivering, and tremor. The presumed pathophysiological mechanism involves brainstem and spinal cord activation of the 1A form of serotonin (5-hydroxytryptamine, or 5- HT) receptor. The incidence of the syndrome is not known. Both sexes have been affected, and patients' ages have ranged from 20 to 68 years. Discontinuation of the suspected serotonergic agent and institution of supportive measures are the primary treatment, although 5-HT receptor antagonists may also play a role. Once treatment is instituted, the syndrome typically resolves within 24 hours, but confusion can last for days, and death has been reported. CONCLUSIONS: The serotonin syndrome is a toxic condition requiring heightened clinical awareness for prevention, recognition, and prompt treatment. Further work is needed to establish the diagnostic criteria, incidence, and predisposing factors, to identify the role of 5-HT antagonists in treatment, and to differentiate the syndrome from neuroleptic malignant syndrome.

This article has been cited by other articles:

N. Ahuja and A. J. Cole
Hyperthermia syndromes in psychiatry
Adv. Psychiatr. Treat., May 1, 2009; 15(3): 181 - 191.
[Abstract] [Full Text] [PDF]

G. Shanmugam, B. Kent, T. Alsaiwadi, and R. Baskett
Serotonin syndrome following cardiac surgery
Interactive CardioVascular and Thoracic Surgery, August 1, 2008; 7(4): 656 - 657.
[Abstract] [Full Text] [PDF]

C. Frank
Recognition and treatment of serotonin syndrome
Can Fam Physician, July 1, 2008; 54(7): 988 - 992.
[Full Text] [PDF]

G. M Alnwick
Misdiagnosis of Serotonin Syndrome as Fibromyalgia and the Role of Physical Therapists
Physical Therapy, June 1, 2008; 88(6): 757 - 765.
[Abstract] [Full Text] [PDF]

N Jackson, J Doherty, and S Coulter
Neuropsychiatric complications of commonly used palliative care drugs
Postgrad. Med. J., March 1, 2008; 84(989): 121 - 126.
[Abstract] [Full Text] [PDF]

S. Hartikainen, E. Lonnroos, and K. Louhivuori
Medication as a Risk Factor for Falls: Critical Systematic Review
J. Gerontol. A Biol. Sci. Med. Sci., October 1, 2007; 62(10): 1172 - 1181.
[Abstract] [Full Text] [PDF]

P. N. Karamanakos, P. Pappas, V. A. Boumba, C. Thomas, M. Malamas, T. Vougiouklakis, and M. Marselos
Pharmaceutical Agents Known to Produce Disulfiram-Like Reaction: Effects on Hepatic Ethanol Metabolism and Brain Monoamines
International Journal of Toxicology, September 1, 2007; 26(5): 423 - 432.
[Abstract] [Full Text] [PDF]

E. M. Altman and G. H. Manos
Serotonin Syndrome Associated With Citalopram and Meperidine
Psychosomatics, August 1, 2007; 48(4): 361 - 363.
[Full Text] [PDF]

K. J. Looper
Potential Medical and Surgical Complications of Serotonergic Antidepressant Medications
Psychosomatics, February 1, 2007; 48(1): 1 - 9.
[Abstract] [Full Text] [PDF]

B. J. Piper, H. L. Vu, M. G. Safain, A. J. Oliver, and J. S. Meyer
Repeated Adolescent 3,4-Methylenedioxymethamphetamine (MDMA) Exposure in Rats Attenuates the Effects of a Subsequent Challenge with MDMA or a 5-Hydroxytryptamine1A Receptor Agonist
J. Pharmacol. Exp. Ther., May 1, 2006; 317(2): 838 - 849.
[Abstract] [Full Text] [PDF]

F. J. Huyse, D. J. Touw, R. S. van Schijndel, J. J. de Lange, and J. P.J. Slaets
Psychotropic Drugs and the Perioperative Period: A Proposal for a Guideline in Elective Surgery
Psychosomatics, February 1, 2006; 47(1): 8 - 22.
[Abstract] [Full Text] [PDF]

H. Karunatilake and N. A Buckley
Serotonin Syndrome Induced by Fluvoxamine and Oxycodone
Ann. Pharmacother., January 1, 2006; 40(1): 155 - 157.
[Abstract] [Full Text] [PDF]

P. K. Gillman
Monoamine oxidase inhibitors, opioid analgesics and serotonin toxicity
Br. J. Anaesth., October 1, 2005; 95(4): 434 - 441.
[Abstract] [Full Text] [PDF]

Z. Bogdanovic, J. R Nalamati, J. K Kilcullen, and S. Dhuper
Antidepressant-Induced Adverse Reactions in a Patient with Hemorrhagic Stroke
Ann. Pharmacother., October 1, 2005; 39(10): 1755 - 1757.
[Abstract] [Full Text] [PDF]

G. Koren, D. Matsui, A. Einarson, D. Knoppert, and M. Steiner
Is maternal use of selective serotonin reuptake inhibitors in the third trimester of pregnancy harmful to neonates?
Can. Med. Assoc. J., May 24, 2005; 172(11): 1457 - 1459.
[Full Text] [PDF]

E. L. Moses-Kolko, D. Bogen, J. Perel, A. Bregar, K. Uhl, B. Levin, and K. L. Wisner
Neonatal Signs After Late In Utero Exposure to Serotonin Reuptake Inhibitors: Literature Review and Implications for Clinical Applications
JAMA, May 18, 2005; 293(19): 2372 - 2383.
[Abstract] [Full Text] [PDF]

S. Wee, K. G. Anderson, M. H. Baumann, R. B. Rothman, B. E. Blough, and W. L. Woolverton
Relationship between the Serotonergic Activity and Reinforcing Effects of a Series of Amphetamine Analogs
J. Pharmacol. Exp. Ther., May 1, 2005; 313(2): 848 - 854.
[Abstract] [Full Text] [PDF]

L. Bergeron, M. Boule, and S. Perreault
Serotonin Toxicity Associated with Concomitant Use of Linezolid
Ann. Pharmacother., May 1, 2005; 39(5): 956 - 961.
[Abstract] [Full Text] [PDF]

A. Haddow and M. Wilson
Clomipramine and neuroleptic malignant syndrome: Authors' reply
BMJ, April 2, 2005; 330(7494): 791 - 791.
[Full Text]

E. W. Boyer and M. Shannon
The Serotonin Syndrome
N. Engl. J. Med., March 17, 2005; 352(11): 1112 - 1120.
[Full Text] [PDF]

A. M Haddow, D. Harris, M. Wilson, and H. Logie
Clomipramine induced neuroleptic malignant syndrome and pyrexia of unknown origin
BMJ, December 4, 2004; 329(7478): 1333 - 1335.
[Full Text] [PDF]

A. B Khandat, J. I Nurnberger Jr, and A. Shekhar
Possible mirtazapine-induced rhabdomyolysis
Ann. Pharmacother., July 1, 2004; 38(7): 1321 - 1321.
[Full Text] [PDF]

G. H Manos and S. M Wechsler
Transient Ischemic Attack Reported with Paroxetine Use
Ann. Pharmacother., April 1, 2004; 38(4): 617 - 620.
[Abstract] [Full Text] [PDF]

D. J Houlihan
Serotonin Syndrome Resulting from Coadministration of Tramadol, Venlafaxine, and Mirtazapine
Ann. Pharmacother., March 1, 2004; 38(3): 411 - 413.
[Abstract] [Full Text] [PDF]

J. R. Oesterheld, S. C. Armstrong, and K. L. Cozza
Ecstasy: Pharmacodynamic and Pharmacokinetic Interactions
Psychosomatics, February 1, 2004; 45(1): 84 - 87.
[Abstract] [Full Text] [PDF]

L. I Velez, G. Shepherd, B. A Roth, and F. L Benitez
Serotonin Syndrome with Elevated Paroxetine Concentrations
Ann. Pharmacother., February 1, 2004; 38(2): 269 - 272.
[Abstract] [Full Text] [PDF]

M J Whipp and K E Waterfield
Serotonin syndrome in the differential diagnosis of spinal cord compression
Palliative Medicine, January 1, 2004; 18(1): 69 - 70.
[PDF]

M. E. Cates
Ziprasidone -- not an option for serotonin syndrome
Can. Med. Assoc. J., November 25, 2003; 169(11): 1147 - 1148.
[Full Text] [PDF]

S. D Karki and G.-R. Masood
Author's Reply
Ann. Pharmacother., October 1, 2003; 37(10): 1532 - 1533.
[Full Text] [PDF]

G. K Isbister
Comment: combination risperidone and SSRI-induced serotonin syndrome
Ann. Pharmacother., October 1, 2003; 37(10): 1531 - 1532.
[Full Text] [PDF]

E.J.C. Dunkley, G.K. Isbister, D. Sibbritt, A.H. Dawson, and I.M. Whyte
The Hunter Serotonin Toxicity Criteria: simple and accurate diagnostic decision rules for serotonin toxicity
QJM, September 1, 2003; 96(9): 635 - 642.
[Abstract] [Full Text] [PDF]

K. Laine, T. Heikkinen, U. Ekblad, and P. Kero
Effects of Exposure to Selective Serotonin Reuptake Inhibitors During Pregnancy on Serotonergic Symptoms in Newborns and Cord Blood Monoamine and Prolactin Concentrations
Arch Gen Psychiatry, July 1, 2003; 60(7): 720 - 726.
[Abstract] [Full Text] [PDF]

M. S H Lam and R. J Ignoffo
A guide to clinically relevant drug interactions in oncology
Journal of Oncology Pharmacy Practice, June 1, 2003; 9(2-3): 45 - 85.
[Abstract] [PDF]

P. Birmes, D. Coppin, L. Schmitt, and D. Lauque
Serotonin syndrome: a brief review
Can. Med. Assoc. J., May 27, 2003; 168(11): 1439 - 1442.
[Full Text] [PDF]

H. Connor
Serotonin syndrome after single doses of co-amoxiclav during treatment with venlafaxine
J R Soc Med, May 1, 2003; 96(5): 233 - 234.
[Full Text] [PDF]

I.M. Whyte, A.H. Dawson, and N.A. Buckley
Relative toxicity of venlafaxine and selective serotonin reuptake inhibitors in overdose compared to tricyclic antidepressants
QJM, May 1, 2003; 96(5): 369 - 374.
[Abstract] [Full Text] [PDF]

B. Mokhlesi, J. B. Leikin, P. Murray, and T. C. Corbridge
Adult Toxicology in Critical Care: Part II: Specific Poisonings
Chest, March 1, 2003; 123(3): 897 - 922.
[Full Text] [PDF]

J. E Jacob, M. L Wagner, and J. I Sage
Safety of Selegiline with Cold Medications
Ann. Pharmacother., March 1, 2003; 37(3): 438 - 441.
[Abstract] [Full Text] [PDF]

J.-J. Pan and W. W Shen
Serotonin Syndrome Induced by Low-Dose Venlafaxine
Ann. Pharmacother., February 1, 2003; 37(2): 209 - 211.
[Abstract] [Full Text] [PDF]

D. H. Arnold
Consultation With the Specialist: The Central Serotonin Syndrome: Paradigm for Psychotherapeutic Misadventure
Pediatr. Rev., December 1, 2002; 23(12): 427 - 432.
[Full Text] [PDF]

K. SATO, K. YOSHIDA, H. HIGUCHI, and T. SHIMIZU
Rapid Worsening of Depressive Symptoms in a Patient With Depression After Switching From a TCA to an SSRI
J Neuropsychiatry Clin Neurosci, August 1, 2002; 14(3): 357 - 357.
[Full Text] [PDF]

J. Chu, R. Y. Wang, and N. S. Hill
Update in Clinical Toxicology
Am. J. Respir. Crit. Care Med., July 1, 2002; 166(1): 9 - 15.
[Full Text] [PDF]

E H Wong, N N Chan, K H Sze, and K H Or
Serotonin syndrome in a renal transplant patient
J R Soc Med, January 6, 2002; 95(6): 304 - 305.
[Full Text] [PDF]

R. E. McCUE and M. JOSEPH
Venlafaxine- and Trazodone-Induced Serotonin Syndrome
Am J Psychiatry, December 1, 2001; 158(12): 2088 - 2089.
[Full Text]

S. B. Turkel, J. G. B. Nadala, and M. Z. Wincor
Possible Serotonin Syndrome in Association With 5-HT3 Antagonist Agents
Psychosomatics, June 1, 2001; 42(3): 258 - 260.
[Abstract] [Full Text]

H. C. MARGOLESE and G. CHOUINARD
Serotonin Syndrome From Addition of Low-Dose Trazodone to Nefazodone
Am J Psychiatry, June 1, 2000; 157(6): 1022 - 1022.
[Full Text]

S. A. Bernard and E. Bruera
Drug Interactions in Palliative Care
J. Clin. Oncol., April 1, 2000; 18(8): 1780 - 1799.
[Abstract] [Full Text] [PDF]

N. K Perry
Venlafaxine-induced serotonin syndrome with relapse following amitriptyline
Postgrad. Med. J., April 1, 2000; 76(894): 254 - 254.
[Abstract] [Full Text]

D. J. Fickbohm and P. S. Katz
Paradoxical Actions of the Serotonin Precursor 5-hydroxytryptophan on the Activity of Identified Serotonergic Neurons in a Simple Motor Circuit
J. Neurosci., February 15, 2000; 20(4): 1622 - 1634.
[Abstract] [Full Text] [PDF]

D. L. Laven and L. Oller
Drug Poisoning and Overdose for the Health Professional: Review of Select Over-the-Counter (OTC) and Prescription Medications
Journal of Pharmacy Practice, February 1, 2000; 13(1): 37 - 81.
[Abstract] [PDF]

M. J. Tueth and P. Zuberi
Life-Threatening Psychiatric Emergencies in the Elderly: Overview
J Geriatr Psychiatry Neurol, July 1, 1999; 12(2): 60 - 66.
[Abstract] [PDF]

R. J. Westphal
Serotonin Syndrome
Journal of the American Psychiatric Nurses Association, June 1, 1999; 5(3): 97 - 102.
[PDF]

C. E. Schwartz, J. F. Knudsen, B. Friedman, M. Chen, and J. E. Goldwasser
A Surfeit of Serotonin: Sumatriptan and Serotonergic Antidepressants
Arch Intern Med, May 24, 1999; 159(10): 1141 - 1142.
[Full Text] [PDF]

A Walubo and D Seger
Fatal multi-organ failure after suicidal overdose with MDMA, `Ecstasy': case report and review of the literature
Human and Experimental Toxicology, February 1, 1999; 18(2): 119 - 125.
[Abstract] [PDF]

P. K. Gillman
The serotonin syndrome and its treatment
J Psychopharmacol, January 1, 1999; 13(1): 100 - 109.
[Abstract] [PDF]

C. Kawanishi, T. Hanihara, Y. Shimoda, K. Suzuki, N. Sugiyama, H. Onishi, T. Miyakawa, Y. Yamada, and K. Kosaka
Lack of Association Between Neuroleptic Malignant Syndrome and Polymorphisms in the 5-HT1A and 5-HT2A Receptor Genes
Am J Psychiatry, September 1, 1998; 155(9): 1275 - 1277.
[Abstract] [Full Text]

J. E. Malberg and L. S. Seiden
Small Changes in Ambient Temperature Cause Large Changes in 3,4-Methylenedioxymethamphetamine (MDMA)-Induced Serotonin Neurotoxicity and Core Body Temperature in the Rat
J. Neurosci., July 1, 1998; 18(13): 5086 - 5094.
[Abstract] [Full Text] [PDF]

R. M. Lane
SSRI-Induced extrapyramidal side-effects and akathisia: implications for treatment
J Psychopharmacol, January 1, 1998; 12(2): 192 - 214.
[Abstract] [PDF]

R. J. Goldberg
Selective Serotonin Reuptake Inhibitors: Infrequent Medical Adverse Effects
Arch Fam Med, January 1, 1998; 7(1): 78 - 84.
[Abstract] [Full Text] [PDF]

P. J. Goodnick and B. J. Goldstein
Selective serotonin reuptake inhibitors in affective disorders -II. Efficacy and quality of life
J Psychopharmacol, January 1, 1998; 12(4_suppl): S21 - S54.
[Abstract] [PDF]

M. Pao
Serotonin Syndrome After Sertraline Overdose in a 5-Year-Old Girl
Arch Pediatr Adolesc Med, October 1, 1997; 151(10): 1064 - 1067.
[Abstract] [PDF]

H. Cohen, R. S. Hoffman, and M. A. Howland
Antidepressant Poisoning and Treatment: A Review and Case Illustration
Journal of Pharmacy Practice, August 1, 1997; 10(4): 249 - 270.
[Abstract] [PDF]

M. J Hodgman, T. G Martin, and E. P Krenzelok
Serotonin syndrome due to venlafaxine and maintenance tranylcypromine therapy
Human and Experimental Toxicology, January 1, 1997; 16(1): 14 - 17.
[Abstract] [PDF]

H. D. Hayes
A 61-Year-Old Man With Parkinson's Disease
JAMA, July 10, 1996; 276(2): 103 - 104.
[Abstract] [PDF]

C.J. Hawley, S. Ratnam, H.A. Pattinson, S.J. Quick, and D. Echlin
Safety and tolerability of combined treatment with moclobemide and SSRIs: a preliminary study of 19 patients
J Psychopharmacol, January 1, 1996; 10(3): 241 - 245.
[Abstract] [PDF]

J. Littrell
Clinical Practice Guidelines for Depression in Primary Care: What Social Workers Need to Know
Research on Social Work Practice, April 1, 1995; 5(2): 131 - 151.
[Abstract] [PDF]

R. Lane, D. Baldwin, and S. Preskorn
The SSRIs: advantages, disadvantages and differences
J Psychopharmacol, January 1, 1995; 9(2_suppl): 163 - 178.
[Abstract] [PDF]

D. E. King, D. H. Finestone, and J. G. Peden
Combination Antidepressant Therapy in Primary Care
Arch Fam Med, December 1, 1994; 3(12): 1088 - 1092.
[Abstract] [PDF]

R. I. Lappin and E. L. Auchincloss
Treatment of the Serotonin Syndrome with Cyproheptadine
N. Engl. J. Med., October 13, 1994; 331(15): 1021 - 1022.
[Full Text]

C.J. Hawley, A.G. Roberts, and M.H. Walker
Tolerability of combined treatment with lithium and paroxetine: 19 cases treated under open conditions
J Psychopharmacol, January 1, 1994; 8(4): 266 - 267.
[Abstract] [PDF]

D. Ames and W. C. Wirshing
Ecstasy, the Serotonin Syndrome, and Neuroleptic Malignant Syndrome--A Possible Link?
JAMA, February 17, 1993; 269(7): 869 - 869.
[Abstract] [PDF]

R. Friedman
Ecstasy, the Serotonin Syndrome, and Neuroleptic Malignant Syndrome--A Possible Link?-Reply
JAMA, February 17, 1993; 269(7): 869 - 870.
[Abstract] [PDF]

Get information about faster international access.