Diphenhydramine overdose and serotonin syndrome

I READ WITH INTEREST the case presented by Tanaka et al. recently published in your journal.1 They reported, for the first time, a case of central anticholinergic syndrome due to diphenhydramine overdose that shared some clinical features of serotonin syndrome. They managed their case with intravenous drip infusion of fluids and oral administration of lorazepam. The patient's abnormal vital signs, myoclonus, hyperreflexia, and mental status returned to normal within 2–3 days. It can be suggested that administration of cyproheptadine could have improved the patient's condition earlier. As you know, there are seven serotonin receptor families (5-HT1 to 5-HT7), which are further subdivided into groups based on different activities in neural and peripheral organ systems.2 As the authors themselves have also mentioned, serotonin syndrome is thought to be due to excessive stimulation at certain central nervous system 5-HT receptors (i.e. 5-HT-2A, 5-HT-1A, and 5-HT-3).3 Cyproheptadine is a first-generation, histamine-1 receptor-blocking agent with non-specific antagonist properties at 5HT-1A and 5HT-2A receptors.4 It has been shown that patients with mild to moderate symptoms of serotonin syndrome that are not hyperthermic typically respond to this pharmacological agent within 30 min to 2 h of administration.5, 6