Correspondence
Treatment of the Serotonin Syndrome with Cyproheptadine
N Engl J Med 1994; 331:1021-1022October 13, 1994
- Article
To the Editor:
The serotonin syndrome consists of behavioral, neuromuscular, and autonomic changes that result from increased activity of serotonin (5-hydroxytryptamine) in the central nervous system.1 Its symptoms and signs include confusion, fever, diaphoresis, hyperreflexia, ataxia, and myoclonus. The syndrome usually results from the concurrent use of two serotonergic medications, most often a monoamine oxidase inhibitor and either tryptophan or an inhibitor of serotonin reuptake, such as fluoxetine (Prozac) or sertraline (Zoloft). Because of the long-lasting serotonergic activity of both monoamine oxidase inhibitors and inhibitors of serotonin reuptake, however, the syndrome can occur when one drug is discontinued and the other is started weeks later. With supportive therapy alone, the syndrome usually resolves completely within 24 hours after discontinuation of the drug, but prolonged symptoms and even fatal outcomes have occurred.
Serotonin-receptor blockers can prevent the serotonin syndrome in animals, and would seem to be promising agents for the treatment of the syndrome in humans. The literature contains only one such case, that of a patient in whom the serotonin syndrome responded to treatment with methysergide but required three days to resolve completely.2 Cyproheptadine, an antihistamine with both antiserotonergic and anticholinergic properties, has been used successfully in animals, but we are unaware of its use in humans for this purpose. We used cyproheptadine to induce rapid and complete resolution of the serotonin syndrome.
The patient was a 26-year-old woman who had taken fluoxetine and sertraline for depression in the past without important adverse effects. She regularly took trazodone at bedtime to help her sleep but did not report taking any other medications. Eight weeks before presentation she began treatment with the monoamine oxidase inhibitor isocarboxazid (Marplan) in doses of up to 50 mg per day, but the medication was not helpful, and it was tapered over a period of three days and then discontinued. Eleven days after her last dose of isocarboxazid, she took a single 100-mg dose of sertraline. About two hours later restlessness and twitching of her legs developed. She called her psychiatrist, who immediately suspected the serotonin syndrome and referred her to the emergency department.
When examined there, the patient had profuse diaphoresis, incessant bouncing and stamping movements of her legs, tachycardia, and mild tachypnea, but her temperature and blood pressure were normal. She was calm and completely lucid. Physical examination revealed dilated (6 mm) but reactive pupils, generalized hyperreflexia, involuntary dancelike movements of the legs (chorea), and spasmodic contractions of her abdominal and lower back muscles, which threw her backward into lordotic postures (opisthotonos).
She was treated with small doses of diazepam, 5 mg intravenously, and propranolol, 1 mg intravenously, which had little or no effect. She then was given 4 mg of cyproheptadine orally. Within 30 minutes her symptoms subsided. About 1 hour later the symptoms began to worsen again; she was given a second 4-mg dose, and within 30 minutes her symptoms had resolved completely. Three hours after receiving the initial dose of cyproheptadine, urinary retention developed, which resolved three hours later. The patient's movement and urinary symptoms did not recur, and no new symptoms developed.
As the use of serotonergic antidepressant drugs continues to increase, psychiatrists and especially emergency physicians should expect to see increasing numbers of patients with the serotonin syndrome. From our experience with this patient, we suggest that cyproheptadine may be a safe, rapidly effective treatment. Physicians should be aware, however, of its anticholinergic effects (such as urinary retention), which may be potentiated by monoamine oxidase inhibitors.
2 ReferencesRichard I. Lappin, M.D., Ph.D.
Elizabeth L. Auchincloss, M.D.
New York Hospital, New York, NY 100211
Sternbach H . The serotonin syndrome. Am J Psychiatry 1991;148:705-713
Web of Science | Medline2
Sandyk R . L-Dopa induced “serotonin syndrome” in a Parkinsonian patient on bromocriptine. J Clin Psychopharmacol 1986;6:194-195
CrossRef | Web of Science | Medline
- Citing Articles (29)
Citing Articles
1
Alexandre Chan, Terence Rong De Ng, Kevin Yi-Lwern Yap. (2012) Clinically–relevant anticancer-antidepressant drug interactions. Expert Opinion on Drug Metabolism & Toxicology 8:2, 173-199
CrossRef2
K.Y.-L. YAP, W.L. TAY, W.K. CHUI, A. CHAN. (2011) Clinically relevant drug interactions between anticancer drugs and psychotropic agents. European Journal of Cancer Care 20:1, 6-32
CrossRef3
Ashley N. Webb, Prashant Joshi. 2011. Toxidromes and Their Treatment. , 1451-1462.
CrossRef4
L. F. MOHAMMAD-ZADEH, L. MOSES, S. M. GWALTNEY-BRANT. (2008) Serotonin: a review. Journal of Veterinary Pharmacology and Therapeutics 31:3, 187-199
CrossRef5
Erica L. Liebelt. (2008) An Update on Antidepressant Toxicity: An Evolution of Unique Toxicities to Master. Clinical Pediatric Emergency Medicine 9:1, 24-34
CrossRef6
Kevin C. Osterhoudt, Rakesh Mistry. (2007) A Boy With Tremor, Diaphoresis, and Altered Behavior. Pediatric Emergency Care 23:6, 419-421
CrossRef7
P Paruchuri, D Godkar, D Anandacoomarswamy, K Sheth, S Niranjan. (2006) Rare Case of Serotonin Syndrome With Therapeutic Doses of Paroxetine. American Journal of Therapeutics 13:6, 550-552
CrossRef8
Diane P. Calello, Kevin C. Osterhoudt, Fred M. Henretig. (2006) New and Novel Antidotes in Pediatrics. Pediatric Emergency Care 22:7, 523-530
CrossRef9
Daniel E. Rusyniak, Jon E. Sprague. (2005) Toxin-Induced Hyperthermic Syndromes. Medical Clinics of North America 89:6, 1277-1296
CrossRef10
Geoffrey K Isbister, Nick A Buckley. (2005) The Pathophysiology of Serotonin Toxicity in Animals and Humans. Clinical Neuropharmacology 28:5, 205-214
CrossRef11
Naeem Tahir. (2004) Serotonin Syndrome as a Consequence of Drug-Resistant Infections: An Interaction Between Linezolid and Citalopram. Journal of the American Medical Directors Association 5:2, 111-113
CrossRef12
Andis Graudins, Robert P Dowsett, Christopher Liddle. (2002) The toxicity of antidepressant poisoning: Is it changing? A comparative study of cyclic and newer serotonin-specific antidepressants. Emergency Medicine Australasia 14:4, 440-446
CrossRef13
N. J. Langford. (2002) Serotonin syndrome. Adverse Drug Reaction Bulletin &NA;:217, 831-834
CrossRef14
Theresa A. Zesiewicz, Sujatha Borra, Robert A. Hauser. (2002) Clozapine withdrawal symptoms in a Parkinson's disease patient. Movement Disorders 17:6, 1365-1367
CrossRef15
Koichi Nisijima, Tatuki Yoshino, Kunio Yui, Satoshi Katoh. (2001) Potent serotonin (5-HT)2A receptor antagonists completely prevent the development of hyperthermia in an animal model of the 5-HT syndrome. Brain Research 890:1, 23-31
CrossRef16
M. Chambost, L. Liron, D. Peillon, C. Combe. (2000) syndrome serotoninergique lors d’une intoxication par la fluoxetine chez une patiente prenant du moclobemide. Canadian Journal of Anesthesia/Journal canadien d'anesthésie 47:3, 246-250
CrossRef17
Steven Hamilton, Kevin Malone. (2000) Serotonin Syndrome During Treatment With Paroxetine and Risperidone. Journal of Clinical Psychopharmacology 20:1, 103-105
CrossRef18
Craig Castle, Paula Jablonski, Graeme Thomson, James Taylor, Anthony Kambourakis, Steven Troupakis. (1998) Interaction of sertraline and moclobemide induces the serotonin syndrome in the rat. Emergency Medicine 10:3, 234-239
CrossRef19
Ann Isaacs. (1998) Depression & your patient. American Journal of Nursing 98:7, 26-31
CrossRef20
Melinda S. Lantz, Eric N. Buchalter, Vincent Giambanco. (1998) Letter to the Editor: Serotonin syndrome following the administration of tramadol with paroxetine. International Journal of Geriatric Psychiatry 13:5, 343-345
CrossRef21
Joseph G. Rella, Robert S. Hoffman. (1998) Possible Serotonin Syndrome from Paroxetine and Clonazepam. Clinical Toxicology 36:3, 257-258
CrossRef22
Jacob T. Abraham, Richard Brown, Herbert Y. Meltzer. (1997) Clozapine treatment of persistent paroxysmal dyskinesia associated with concomitant paroxetine and sumatriptan use. Biological Psychiatry 42:2, 144-146
CrossRef23
Roger Lane, David Baldwin. (1997) Selective Serotonin Reuptake Inhibitor-Induced Serotonin Syndrome. Journal of Clinical Psychopharmacology 17:3, 208-221
CrossRef24
P. Ken Gillman. (1997) Serotonin Syndrome Treated With Chlorpromazine. Journal of Clinical Psychopharmacology 17:2, 128-129
CrossRef25
Pardeep K. Nijhawan, Gail Katz, Stephen Winter. (1996) Psychiatric illness and the serotonin syndrome. Critical Care Medicine 24:6, 1086-1089
CrossRef26
P ROBERT, J SENARD, M FABRE, C CABOT, B CATHALA. (1996) Syndrome sérotoninergique lors d'une intoxication aiguë aux antidépresseurs. Annales Françaises d’Anesthésie et de Réanimation 15:5, 663-665
CrossRef27
Gro Laier. (1996) The serotonin syndrome: Definition and eause. Nordic Journal of Psychiatry 50:3, 249-260
CrossRef28
E. -L. Sainio, K. Pulkki, S. N. Young. (1996) L-Tryptophan: Biochemical, nutritional and pharmacological aspects. Amino Acids 10:1, 21-47
CrossRef29
&NA;. (1994) Sertraline interaction. Reactions Weekly &NA;:524, 11
CrossRef
