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Am J Psychiatry. 1992 May;149(5):587-95.

Gender differences in pharmacokinetics and pharmacodynamics of psychotropic medication.

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Department of Psychiatry, Harvard Medical School, Boston, MA.



This review explores the theoretical background for and empirical evidence supporting gender-related differences in pharmacokinetics and pharmacodynamic properties of psychotropic medications.


The authors reviewed all English-language articles on this topic that involved original research using human subjects.


Limited evidence suggests that young women seem to respond better to and require lower doses of antipsychotic agents and benzodiazepines than young men. The administration of exogenous hormones interacts with medications, changing plasma levels and possibly conferring greater risks for toxicity. Young women may have an enhanced response to nontricyclic antidepressants.


Too little basic and clinical research has been conducted on sex differences in therapeutic effects and side effects of psychopharmacological treatments. Addressing these differences as well as similarities will lead to safer and more effective treatment for all patients.


A review of the English-language literature on original research with human subjects concerning sex differences in pharmacokinetics and psychotropic agents was attempted. With respect to absorption and bioavailability, women may secrete less gastric acid, and progesterone in the luteal phase slowed gastric emptying. Drugs with high affinity for adipose tissue (diazepam) would be distributed more in females with a lower ratio of lean body mass to adipose tissue. Yet, over time half-life may be prolonged with higher serum levels in patients with less lean body mass. The 1st-pass metabolism of drugs and later extensive metabolizing for systemic circulation are carried out in the liver. The menstrual cycle also affects gastric motility as dilution via fluid retention results in lower plasma levels. Estrogen may reduce monoamine oxidase activity and progesterone may increase it. Women taking oral contraceptives and diazepam during menstruation become relatively intoxicated. With respect to antipsychotic agents higher fluphenazine levels were found in women, and they required 1/2 the dose of fluspiriline as men. Women improved more after pimozide and chlorpromazine treatment than men. The incidence of severe tardive dyskinesia was higher in postmenopausal women possibly attributable to estrogen loss. Oral contraceptives reduced the clearance of benzodiazepines resulting in slower peak levels of diazepam while being off pills led to impairment of cognitive and psychomotor tasks. Temazepam and oxazepam also cleared more slowly in women. Among antidepressant agents MAO inhibitors produced better results in women than did tricyclic antidepressants. Lithium-induced hypothyroidism predominates in women as does thyroid disease, and possibly rapid-cycling bipolar illness is also linked to this condition.

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