Sex Differences in the Pharmacokinetics of Antidepressants: Influence of Female Sex Hormones and Oral Contraceptives

Women are twice as likely to develop depression as men. Moreover, the symptoms they experience also show sex differences: women tend to develop depression at an earlier age and show more severe symptoms than men. Likewise, the response to antidepressant pharmacotherapy appears to have sex differences. These differences can partially be explained by differences in pharmacokinetic properties (i.e., absorption, distribution, metabolism, and excretion) of drugs in males and females. More recent research has shown that sex hormones may influence all these previously named pharmacokinetic processes. As concentrations of sex hormones vary throughout the female lifespan, these hormonal variations can have effects on therapeutic responses to antidepressants as well as the occurrence of adverse events. The purpose of this paper is therefore to review the literature reporting on the effects of female sex hormones on the pharmacokinetics of antidepressants and to discuss and evaluate the implications of changes in levels of sex hormones throughout life for the treatment of depression.