Toward Hormone-Aware Psychopharmacology: Gender-Specific Pharmacokinetics and Pharmacodynamics of Psychoactive Drugs in Women
DOI:
https://doi.org/10.35451/jfm.v9i1.3989Keywords:
Sex differences, Psychotropic drugs, Pharmacokinetics, Hormonal contraceptives, Premenstrual dysphoric disorderAbstract
Background: Biological sex differences are important determinants of responses to psychotropic drugs. Women exhibit significant pharmacokinetic and pharmacodynamic variability due to fluctuations in reproductive hormones. Objective: This narrative review aims to analyze the impact of hormonal phases on mental health therapy in women. Methods: A narrative literature review was conducted on publications from 2021 to 2026. Results: During the third trimester of pregnancy, plasma concentrations of selective serotonin reuptake inhibitors (SSRIs) and serotonin–norepinephrine reuptake inhibitors (SNRIs) decrease substantially, by up to 90% for paroxetine, followed by a postpartum rebound that may increase the risk of toxicity. Additionally, estrogen-containing oral contraceptives induce the UGT1A4 enzyme, reducing lamotrigine concentrations by more than 50% and increasing the risk of toxicity during hormone-free intervals. For antipsychotic therapy, women achieve serum drug concentrations 56–72% higher than men at standard doses, increasing the risk of hyperprolactinemia and QT interval prolongation. Furthermore, the underlying mechanisms of premenstrual dysphoric disorder are associated with impaired GABA-A receptor δ-subunit plasticity in response to the neurosteroid allopregnanolone. Conclusion: Psychopharmacological prescribing for women should adopt a hormone-aware approach, incorporating therapeutic drug monitoring and dose adjustments based on life stages to optimize treatment efficacy and safety.
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Copyright (c) 2026 Revanda Nafa Mustofa, Reynatha C.A. Pangsibidang, M.S.Farm., apt. Rinda Dwi Sartika, M.Farm.
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