Co-administration of combined oral contraceptives and psychotropic drugs - risk of contraceptive failure and adverse events.

Background: Combined oral contraceptives (COCs) and psychotropic drugs (PDs) are commonly used drugs in the female population. Yet, the quantity and quality of previous studies on drug interactions between these two medications is limited.

Objectives: To provide a detailed overview of the concomitant use of COCs and PDs and its potential risk of contraceptive failure and adverse events (AEs) in routine clinical practice.

Study design: A pooled analysis of four large, prospective, multinational cohort studies comprising new users of COCs with and without concomitant PD intake. We used exact matching (variable 1:10 ratio) on region, smoking status, age, and Body Mass Index (BMI) groups. Contraceptive failure and selected AEs occurring within six months after COC initiation were expressed by incidence rates per 100 women-years, crude, and adjusted Cox regression hazard ratios with 95% confidence intervals (CIs) separately for Europe and the United States.

Results: After matching, 8081 COC+PD users (Europe: 2271, United States: 5810) and 70,009 COC-only users (Europe: 22,685, United States: 47,324) were considered for analysis. No significant difference was found for the risk of contraceptive failure between COC+PD and COC-only users. The hazard ratios adjusted for age, BMI, medical history, oral contraceptive user status (i.e., first-time ever user, switcher, restarter after intake break), and education level were 1.4 (95% CI, 0.56 - 3.52) for Europe and 0.8 (95% CI, 0.55 - 1.09) for the United States. The risk of adverse events was 1.5-fold higher in COC+PD users than in COC-only users (Europe: 1.5 [95% CI, 1.13 - 2.02]; United States: 1.5 [95% CI, 1.22 - 1.88]). Most AEs were related to the digestive and genitourinary systems.

Conclusions: No difference in the risk of contraceptive failure was found for COC+PD and COC-only users, while COC+PD users tend to experience more AEs.