An exception, however, is clozapine, the blood levels of which are 30% to 35% higher in women than in men when dosed by efficacy.142-145 Neuroleptic blood levels also do not. appear to differ in men and women even at the same dose. Nonetheless, exceptions include higher olanzapine see more plasma levels in women, even after controlling for body mass index,146 and higher mean plasma, levels of sertindole, which the authors attributed to a higher dose per weight, better absorption, and slower metabolism in women.137 In conclusion, for neuroleptics as for antidepressants Inhibitors,research,lifescience,medical and benzodiazepines, with several notable exceptions (eg, clozapine and olanzapine), plasma levels arc similar in men and women.

Pharmacodynamics While sexual dimorphisms in pharmacokinetics alter the exposure of a tissue to the medication administered, Inhibitors,research,lifescience,medical a considerable degree of variance in the observed effect. potentially resides in differences in the response of the tissue, ic, identical drug exposure of a tissue to a drug may elicit, very different, responses

across Inhibitors,research,lifescience,medical individuals. Differences in tissue response – the pharmacodynamics – may be quite dramatic, seen, for example, in different profiles of side effects or mood destabilization induced by identical levels of gonadal steroids in different, subpopulations of women.147 Antidepressants Most, studies of the effect, of sex on the efficacy of antidepressants have many more female subjects than male subjects, and thus are not adequately powered. Nonetheless, although there is the possibility of reporting bias (ie, selectively publishing studies demonstrating sex differences), substantial evidence suggests that males respond better to tricyclic antidepressants (TCAs) than females. An early study of 250 depressed Inhibitors,research,lifescience,medical patients Inhibitors,research,lifescience,medical by the Medical Research Council reported that imipramine is more effective in men than in women.45

A study of 60 depressed inpatients also found that men responded better to imipramine,148 as did a 4-week study of 55 depressed inpatients treated with imipramine149 and a. large study of 200 patients on imipramine.150 More recently, a. study of 230 depressed patients also described imipramine therapy as more effective in men.151 However, not surprisingly, some studies failed to observe sex differences in response to TCA treatment. An 8week, double-blind clinical trial of imipramine efficacy in 80 depressed patients found clinical mafosfamide improvement, was not significantly related to sex152; a 6-week clinical trial of imipramine and phenelzine efficacy found no sex difference in imipramine response rate153; a study of 29 depressed inpatients found no sex difference in response after 2 weeks of nortriptyline treatment154; an open-label trial of desipramine in 118 dysthymic patients found equal numbers of men and women responded to treatment after 10 weeks155; and a 4-week study of 66 depressed inpatients found no sex difference in treatment response to imipramine.