All antidepressants have side effects, though all patients do not experience all of them or to same degree.[3] Serotonin reuptake inhibitors (SSRIs) are a family of antidepressants considered to be the current standard of drug treatment for major depression. Fluoxetine was the first selective serotonin reuptake inhibitor to be widely available for the treatment of depression and numerous other neuropsychiatric disorders. Fluoxetine is generally safe and well-tolerated. Common adverse effects reported, with the recommended dose of 20 mg/day, are related to the gastrointestinal system and the nervous system. The approved dose range is up to 80 mg/day, but adverse events are more common when higher doses are used.[4] It is an inhibitor of cytochrome P450 (CYP) 2D6 and other CYP enzymes, which increases the potential for drug interactions, though most of them are not clinically important.

SSRI group of antidepressants have fewer adverse events than the tricyclic antidepressants or MAOIs.[5] Serotonin syndrome is a potentially life-threatening complication of SSRI therapy. The syndrome is produced most often by the concurrent use of two or more drugs that increase brainstem serotonin activity and is often unrecognized due to the nonspecific nature of its symptoms. The physiopathological hypothesis is principally supported by excess stimulation of the central (5HT1a) serotonin receptors. This syndrome is characterized by alterations in cognition, behavior, autonomic nervous system function, and neuromuscular activity.[6] The symptoms can be mild (may or may not concern the patient); moderate (toxicity which causes significant distress and deserves treatment, but is not life-threatening); or severe (a medical emergency characterized by rapid onset of severe hyperthermia, muscle rigidity, and multiple organ failure). Diagnosis of serotonin toxicity is often made on the basis of the presence of at least 3 of the 10 clinical features described by Sternbach (agitation, diaphoresis, diarrhea, hyperreflexia, in-coordination, confusion, hypomania, myoclonus, and shivering).[7] Prevention of the syndrome and its early discovery is essential. Several non-selective anti-serotonin therapies have been tested without much success. Withdrawal of the imputable drug often resolves the symptoms within 24 hours. Symptomatic and supportive care remains the pillar of the treatment. While reviewing literature on the treatment of serotonin syndrome, the authors gathered evidence suggestive of efficacy of chlorpromazine and cyproheptadine to treat it. The evidence for cyproheptadine is less substantial, perhaps because the dose of cyproheptadine necessary to ensure blockade of brain 5-HT2 receptors is 20–30 mg, which is higher than that used in the cases reported to date (4–16 mg).[8] Our patient responded to a dose of 20 mg cyproheptadine and 5 mg diazepam. There are few case reports supporting serotonin syndrome caused by fluoxetine but none in a postoperative patient or with the use of fentanyl.[9,10]