Cyproheptadine serotonin syndrome

McDaniel WW Serotonin syndrome early management with cyproheptadine. Ann Pharma-cother 200i 35 870-873. 

Graudins, A., Stearman, A., and Chan, B. (1998) Treatment of the serotonin syndrome with cyproheptadine./ Emerg Med 16 615-619. 

Horowitz, B.Z. and Mullins, M.E. (1999) Cyproheptadine for serotonin syndrome in an accidental pediatric sertraline ingestion. Pe-diatr Emerg Care 15 325-327. 

Serotonin syndrome SSRIs, second generation antidepressants, MAOIs, linezolid, tramadol, meperidine, fentanyl, ondansetron, sumatriptan, MDMA, LSD, St. John s wort, ginseng Hypertension, hyperreflexia, tremor, clonus, hyperthermia, hyperactive bowel sounds, diarrhea, mydriasis, agitation, coma onset within hours Sedation (benzodiazepines), paralysis, intubation and ventilation consider 5-HT2 block with cyproheptadine or chlorpromazine... 

The major clinical applications of cyproheptadine are in the treatment of the smooth muscle manifestations of carcinoid tumor and in cold-induced urticaria. The usual dosage in adults is 12-16 mg/d in three or four divided doses. It is of some value in serotonin syndrome, but because it is available only in tablet form, cyproheptadine must be crushed and administered by stomach tube in unconscious patients. 

Serotonin syndrome after a single dose of sertraline 100 mg has been reported in a 16-year-old girl (6). It responded to a single 4 mg dose of the serotonin antagonist cyproheptadine. 

There was therapeutic benefit from cyproheptadine in a case of serotonin syndrome in a 2-year-old girl who accidentally swallowed ten 50 mg tablets of sertraline (7). 

Treatment of an overdose of the atypical antidepressants and SSRIs is directed primarily toward decontamination of the gastrointestinal tract with activated charcoal, symptomatic treatment, and general supportive care. Management of the serotonin syndrome involves discontinuation of the serotinergic agent and supportive therapy. Beu-zodiazepines, propranolol, and cyproheptadine, a serotonin antagonist, have been used successfully. ... 

Serotonin syndrome. Anecdotal case reports suggest benefit with cyproheptadine (Periactin ), 4 mg orally (PO) every hour for 3- doses (see p 430) or methysergide, 2 mg PO every 6 hours for 3-4 doses. 

B. Specific drugs and antidotes. For suspected serotonin syndrome, anecdotal reports claim benefit from cyproheptadine (Periactin), 4 mg orally every hour for 3 doses, or methysergide (Sansert), 2 mg orally every 6 hours for 3 doses, presumably because of the serotonin antagonist effects of these drugs. 

Graudins A et al Treatment of the serotonin syndrome with cyproheptadihe. J Emerg Med 1998 16(4) 615-619. [PMID 9696181] (Case series of five patients treated successfully with cyproheptadine 4-8 mg orally.)... 

I. Pharmacology. Cyproheptadine is a first-generation, histamine-1 blocker with nonspecific serotonin (5-HT) antagonism. The administration of cyproheptadine to patients with serotonin syndrome appears to antagonize excessive stimulation of 5-HTia and 5-HT2 receptors, resulting in improvements in clinical symptoms (based on anecdotal case reports). 

Information seems to be limited to these reports but it would now be prudent to be alert for a reduction in efiicacy or an adverse response if cyproheptadine is given with any MAOI or RIMA. The manufacturer of cyproheptadine actually contraindicates concurrent used with MAOIs. However, there appears to be no reason why cyproheptadine cannot be used to treat the serotonin syndrome occurring in a patient on an MAOI. 

Graudins A, StearmanA, ChanB. Treatment ofthe serotonin syndrome with cyproheptadine. JEmergMed 99S) 16, 615-19. 

Four elderly patients taking sertraline developed symptoms characteristic of the serotonin syndrome within 2 to 4 days of also taking St John s wort 300 mg, either two or three times daily. The symptoms included dizziness, nausea, vomiting, headache, anxiety, confusion, restlessness, and irritability. Two of them were treated with oral cyproheptadine 4 mg either two or three times daily, and the symptoms of all of them resolved within a week. They later resumed treatment with sertraline without problems. A search of Health Canada s database of spontaneous adverse reactions from 1998 to 2003 found 2 cases of suspected serotonin syndrome as a result of an interaction between sertraline and St John s wort. ... 

A 21-year-old man developed the serotonin syndrome when he took one tablet of paroxetine only one day after stopping desipramine, which he had taken for 5 days. He recovered after treatment with cyproheptadine. A woman taking paroxetine 30 mg daily developed the serotonin syndrome (tachycardia, delirium, bizarre movements, myoclonus) within 2 hours of taking a single 50-mg dose of imipramine. She recovered when treated with intravenous fluids, sedation and cyproheptadine. ... 

There is no specific antidote to duloxetine, but if serotonin syndrome ensues, specific treatment (such as with cyproheptadine and/or temperature control) may be considered. In a case of acute overdose, treatment should consist of general measures employed in the management of overdose with any drug. 

Cyproheptadine, a serotonin and histamine receptor- and muscarinic cholinergic receptorblocking agent, has been used in the treatment of postgastrectomy dumping syndrome and the intestinal hypermotility seen with carcinoid. 

---