An 11-year retrospective review of cyproheptadine use in serotonin syndrome cases reported to the California Poison Control System

Abstract

Summary What is known Cyproheptadine is a serotonin and histamine antagonist that has been suggested as a treatment for serotonin syndrome in case reports. Objective We sought to examine the differences between outcomes and treatment recommendations in patients who received and did not receive cyproheptadine for a probable serotonin syndrome. Methods A retrospective review of cases reported to the California Poison Control System between 2006 and 2017 involving cyproheptadine administration or consideration for treatment of a probable serotonin syndrome. Results and discussion A total of 1420 cases were identified and 288 cases met the inclusion criteria. Of these, 68 (23.1%) patients received cyproheptadine treatment and were significantly older (mean age 49.7 vs 33.5 years, P < 0.00001), intubated (n = 35, 51% vs n = 62, 28%, P < 0.05) and, although not statistically significant, were more frequently admitted to a critical care unit (n = 56, 82.3% vs n = 154, 70.0%, P = 0.09). There were no significant differences in serious outcomes (moderate or worse effects) or hospitalization rates (OR, 1.09, 95% CI, 0.49‐2.64 and OR, 1.99, 95% CI, 0.86‐4.58). There were eight fatalities, of which two patients received cyproheptadine. All fatalities were acute polypharmacy ingestions and had manifested severe symptoms (seizures, hypotension or hyperthermia) either prior to the administration or consideration of cyproheptadine therapy. Cyproheptadine was not administered in 138 (48%) cases primarily due to minimal clinical severity and patient improvement (43%), and not recommended in 82 (28%) cases for reasons from waiting for response to other supportive measures (30%), limited evidence of efficacy (28%) and undetermined diagnosis (14.6%). What is new and conclusion The benefits of and indications for cyproheptadine are uncertain and questionable for the management of a serotonin syndrome. Future recommendations on its use should be based on diagnostic criteria, severity of symptoms and management in conjunction with other supportive measures.

Doxepin Exacerbates Renal Damage, Glucose Intolerance, Nonalcoholic Fatty Liver Disease, and Urinary Chromium Loss in Obese Mice

“…Furthermore, doxepin may act as a nonselective serotonin receptor/reuptake inhibitor for the serotonin transporter [5]. Another beneficial effect of a strong serotonin antagonist such as doxepin is that it may counteract the most serious, even lethal, side effects of some antidepressants (e.g., serotonin syndrome, which has a ≤5.9% mortality rate), particularly when administered alongside serotonin reuptake inhibitors to treat mental disorders [6].…”

Antidepressant‐induced serotonin syndrome in older patients: a cross‐sectional study

“…In a recent systematic review, cyproheptadine use was reported to be 16% among 56 SS patients with a mean age of 42 24 . In contrast, in another previous study, 23% of 288 patients (mean age 49.7) were treated with cyproheptadine and reported no benefit for worse outcomes of SS in patient populations, concluding that the use of cyproheptadine is questionable 26 . Accordingly, in this study, 37% of patients with SS received cyproheptadine more frequently than in previous reports, and this might be the reason why none of our patients progressed severely.…”

Safety of Cyproheptadine, an Orexigenic Drug. Analysis of the French National Pharmacovigilance Data-Base and Systematic Review

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