Pharmacokinetic and pharmacodynamic effects of psychotropic medications: Differences between sexes

Abstract

The gender based or gender sensitive pharmacology is a new research area. Differences among sexes are observed in several parameters of their pharmacokinetic which may relate to alteration of their pharmacodynamic as well. Most psychotropics are given per os, and the greater part of their absorption takes place in the small intestine. Premenopausal women have slower gastric emptying times and lower gastrointestinal blood flow which probably reduces the extent of drug absorption. The distribution of drugs is influenced by the relative lower body mass index, the lower blood volume and flow and the greater percentage of body fat of women. Further, the elimination and renal clearance is reduced in women and the hepatic metabolism differ between sexes. Besides, women differ from men in physiological conditions which may have an impact on the psychotropic medication and dosage required for efficacy and response. Women are exposed to monthly hormonal fluctuations (menstruation), pregnancy, puerperium, menopause and use of contraceptives or synthetic hormonal replacement therapies. Throughout of these conditions changes may occur in total body water, in renal clearance, cardiovascular and autoimmune system, which may cause fluctuations in the activity of the psychotropics, changes in the central neurotransmitters, in the number and sensitivity of the receptors, and the general metabolism as well. Despite the fact that women are the primer consumers of psychotropic medication, taking more psychotropics as well as more multiple medications than men, little attention has been paid to sex differences in psychopharmacology. Till recently women were under-represented or excluded from most of the pharmacological clinical trials. The treatment guidelines for psychotropic medication are based on studies verified and investigated almost exclusively in men. Results from such studies were generalized and recommended for use in the clinical practice without any critique and justification between the sexes. In conclusion, women compared to men, tend to have a greater bioavailability and slower elimination of drugs leading to higher concentrations of free circulating drugs in serum and causing more side effects and adverse reactions to the psychotropic medication than men do. In general, women require lower doses of antidepressants, antipsychotics and benzodiazepines than men. For safety and efficacy reasons and despite the fact that research is still being carried out to determine the exact differences in pharmacodynamic of several psychotropics between genders, the clinician must be aware of the reported effect of the recommended medications on serum levels and organ tissues both for men and women.