Drug-drug interactions between psychotropic medications and oral contraceptives

Introduction: This is a comprehensive overview of pharmacokinetic drug-drug interactions (DDIs) involving oral contraceptives (OCs) and psychotropic medications. Areas covered: Medline and Embase from inception to April 2021 were searched for DDIs between OCs and psychotropic medications. They included case reports/series and cross-sectional, cross-over, placebo-controlled studies of patient cohorts and healthy females. We classified DDIs as: combined hormonal contraceptives (CHCs) acting as victim drugs (i.e. affected by psychotropic co-medications), CHCs as perpetrators, (i.e. affecting the activity of psychotropic co-medications), progestin-derivatives as victim drugs and progestin-derivatives affecting psychotropic co-medications. Alteration ratios reflecting changes in pharmacokinetic parameters before and after the DDI were estimated to approximate the extent of the DDI. Expert opinion: Women taking antiepileptic agents with strong to moderate enzyme-inducing properties (carbamazepine, phenobarbital, phenytoin) or those with moderate to mild enzyme-inducing properties (cenobamate, clobazam, eslicarbazepine, felbamate, oxcarbazepine, rufinamide, topiramate) should avoid OCs. Daily doses of cytochrome P450 1A2 substrates including clozapine may need to be reduced by 50% in women taking concomitant CHCs. Compared to CHCs, the propensity of progestin-only pills for DDIs has been investigated less. We provide a summary table for clinicians containing recommendations based on literature and package inserts; whenever evidence was available, we provided dose-correction factors.