males needed a significantly higher dose of fluspirilene.195 Because estrogen is hypothesized to have a neuroleptic-like effect through its modulation of dopamine receptors, a protective effect, of estrogens has been invoked to explain why female schizophrenic patients have better social adjustment, fewer and less BIBF 1120 manufacturer severe symptoms, and better treatment. response.196 If estrogen impacts neuroleptic response, it, would be expected that female response to neuroleptics would decline after menopause. A study examining this possibility found that, the daily neuroleptic dose for female schizophrenia patients remained constant Inhibitors,research,lifescience,medical from age

20 to 59, with no decline in efficacy corresponding to menopause.197 In a conflicting study, however, females under age 40 were on lower neuroleptic doses than their male peers, but. after age 40, the trend was reversed and female patients required Inhibitors,research,lifescience,medical higher doses than male patients over age 40.198 TTtie overall prevalence of schizophrenia is not sexually dimorphic, but. the age of onset,

is 3 to 6 years earlier in men than in women.199 This raises the possibility that any observed sex differences in response to neuroleptics may reflect differences Inhibitors,research,lifescience,medical in the evolution of the illness expressed at a tissue level. Conclusions There are myriad sex differences in neurobiology, affecting diverse processes from signal transduction to receptor distribution and receptor function to response to stressors. Not. surprisingly, multiple effects of sex on pharmacokinetics have also been Inhibitors,research,lifescience,medical identified.200 Given the multiple steps involved in the translation of a dose of ingested medication to its steady state plasma level, one might imagine that the effects of sex could cither Inhibitors,research,lifescience,medical summatc to produce dramatic sex differences or balance to result in negligible differences.

While considerably more work could and should be done to determine the role played by sex in the pharmacokinetics of psychotropic drugs, the data collected to date suggest that the effect is not likely to be large for most. classes of psychotropic agents. While pharmacodynamic differences are also likely to exist, data to date are exiguous and far from impressive. As befits the complexity of the brain, there are likely few instances in which sex alone comprises many a. large part of the variance in the response to psychotropic medications. Nonetheless, the practitioner must, realize that, under the t right circumstances, sex may strongly influence the response to medication, just as the serotonin transporter genotype (5-HTTLPR) and past, history of adverse life 1 events combine to predict, depression, despite the low predictive value of either of these factors in isolation.201 One size, undoubtedly, does not fit, all, and factors related to sex will provide the attentive careful clinician with possible explanations for an unsatisfactory therapeutic ) response.