Cyproheptadine in treatment of chronic schizophrenia: a double-blind, placebo-controlled study

Objective: There is growing interest in investigating the role of 5-HT receptors in the physiopathology of schizophrenia in particular the negative symptoms. Indeed, newer atypical antipsychotics which interact with 5-HT receptors are more effective in the treatment of negative symptoms compared to typical neuroleptics. We undertook a trial to investigate whether the combination of haloperidol with cyproheptadine, a relatively safe serotonin-blocking agent was more effective than haloperidol alone. Methods: Thirty patients who met the DSM IV criteria for chronic schizophrenia completed the study. Patients were allocated in a random fashion, 15 each to haloperidol 30 mg/day plus cyproheptadine 24 mg/day and haloperidol 30 mg/day plus placebo. Results: Although both protocols significantly decreased the positive and negative symptom score over the trial period, the combination of haloperidol and cyproheptadine showed significant superiority over haloperidol alone in the treatment of the negative symptoms. Conclusion: Cyproheptadine is a relatively safe compound and may be of therapeutic benefit in treating negative symptoms of schizophrenia in combination with typical neuroleptics. However, a larger study to confirm our results is warranted.