Nervousness and depression attributed to oral contraceptives: A double-blind, placebo-controlled study☆

Abstract In a placebo-controlled, double-blind trial of 4 oral contraceptive agents, 398 women were observed over 1,523 cycles and were questioned each cycle regarding certain subjective and objective symptoms including nervousness, depression, and weight gain. The frequency of nervousness and depression in the pretreatment cycle was considerably higher than in the first cycle of treatment with either active agents or placebo. The data fail to show any statistically significant increase over the placebo level in the incidence of depression among oral contraceptive users. There was a somewhat ambiguous increase in nervousness during the first treatment cycle with the 2 high-estrogen preparations. Thirty per cent of the placebo-treated group reported a weight gain of 5 pounds or more during the 4 months of observation in comparison to 19, 20, 28, and 31 per cent of the subjects using the 4 active agents. It would seem that the majority of nervousness, depression, and weight gain noted in oral contraceptive users is either coincidental or associated with the psychological impact of taking these agents, rather than with any pharmacologic effect.