Pharmacokinetics and pharmacodynamics: making clinical sense of sex differences in psychopharmacology

In psychopharmacology, there is a growing interest in potential sex differences regarding psychotropic drugs, currently used or under development. Preclinical research repeatedly identifies sex differences in pharmacokinetics and pharmacodynamics of psychotropic drugs. However, clinical research either does not consistently corroborate such findings or does not necessarily support their clinical significance.

This review succinctly presents the main sex differences in mental disorders (epidemiology, symptomatology), pharmacokinetics (absorption, distribution, metabolism, excretion) and pharmacodynamics (therapeutic effects and adverse drug reactions). The review is based on a curated collection of articles, mainly from the 2000 onwards, listed in the U.S. NLM of Congress, and offers insights on why clinical findings about sex differences in psychopharmacology are inconsistent or of varied clinical importance.

In psychopharmacology, sex differences in pharmacokinetics and pharmacodynamics are progressively discovered. Nevertheless, a significant knowledge gap still exists, resulting in an unclear clinical value of sex differences and perhaps suboptimal use of psychotropic drugs in the context of precision medicine. This review puts into context this knowledge gap and proposes how it can be addressed. Optimization of existing treatments and drug development can benefit by a better appreciation of potential sex differences in psychopharmacology.