Treatment of depression with cyproheptadine

We evaluated the antidepressant activity of cyproheptadine HCl in six patients diagnosed with major depression. This was a double-blind, placebo-controlled, crossover trial with treatment order balanced and randomly assigned. The patients received 4 weeks of treatment with cyproheptadine HCl 4 mg 4 times/day or placebo, followed by 4 weeks of cryproheptadine HCl 8 mg 4 times/day or placebo, followed by a crossover to cyproheptadine HCl or placebo. Each subject had a Hamilton Depression Rating Scale assessment and a 1-mg dexamethasone suppression test completed immediately before treatment and at 4-week intervals throughout the study. Two patients had nonsuppressible dexamethasone suppression tests and could not tolerate cyproheptadine due to anxiety and irritability. Four patients had suppressible dexamethasone suppression tests and had lower scores on the Hamilton Depression Rating Scale during treatment with cyproheptadine (p < 0.01, Student's t test for paired observations). Cyproheptadine HCl may be useful in treating a subset of patients with major depression who have a suppressible dexamethasone suppression test.