Vol 6 n° 1 - Predictors of Response to Treatment in Neuropsychiatry
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3 9 ne of the elusive goals of pharmacotherapy is the ability to identify the relevant characteristics of a patient with a particular disorder in such a way as to per- mit selection of the best pharmacological agent: the med- ication with the greatest likelihood of effectiveness and the least likelihood of adverse or undesirable effects. Despite the considerable number of treatments in our psychotherapeutic armamentarium, any individual treat- ment applied to a group of persons with a given disorder will leave an unacceptably high percentage nonrespon- sive, again consequent to lack of efficacy or inability to tolerate the treatment.To increase the odds of therapeu- tic success, it is incumbent on clinicians to consider the multitude of factors that may influence response to a par- ticular medication, eg, prior response to that medication, family history of response, family history of psychiatric disorders, tolerance of side effects, personality style, his- torical  factors  (eg,  history  of  hypomania  or  suicide attempts), symptom  constellation  (eg, atypical  symp- toms), and coincident medical problems (eg, hepatic dys- function). An additional factor that increasingly may inform treatment decisions is sex. The following article will review both the theoretical evidence for, and the practical demonstrations of, the impact of gender and sex steroids on the response to treatment. The sexually dimorphic brain Two papers in the 1950s and 1960s were critical in demon- strating that the brain, like the gonads, was sexually dimor- phic. First, Phoenix et al1 showed that prenatal exposure of a female guinea pig to testosterone resulted in masculin- ization and defeminization of behavior upon reexposure to  testosterone  in  adulthood. This  ability  of  gonadal steroids, when administered perinatally, to change the repertoire  of  adult  behavioral  response  to  the  same steroid—a process Phoenix et al called “organization”— P h a r m a c o l o g i c a l   a s p e c t s Keywords: sex; psychotropic drug; pharmacokinetics; antidepressant; neuroleptic; pharmacodynamics Author  affiliations:  Behavioral  Endocrinology  Branch,  National  Institute  of Mental  Health,  National  Institutes  of  Health,  Department  of  Health  and Human Services, Bethesda, Md, USA Address  for  correspondence:  David  R.  Rubinow,  MD,  Building  10,  Room 3N238, 10 Center Dr MSC 1276, Bethesda MD 20892-1276, USA
(e-mail: rubinowd@intra.nimh.nih.gov) O Copyright © 2004 LLS SAS.  All rights reserved www.dialogues-cns.org Sex-dependent modulation of treatment response David R. Rubinow, MD; Molly Moore, BA The response to a psychotropic medication reflects char- acteristics of both the medication and the substrate, ie, the individual receiving the medication. Sex is an indi- vidual  characteristic  that  influences  all  elements  of the pharmacokinetic process—absorption, distribution, metabolism, and elimination. The effects of sex on these components of the pharmacokinetic process often coun- terbalance one another to yield minimal or varying sex- ual differences in blood levels achieved. However, sex also appears to influence pharmacodynamics, the tissue response to a given level of medication. Consideration by the practitioner of sex as a possible contributing fac- tor to treatment nonresponse will enhance the efficacy and precision of clinical interventions. © 2004, LLS SAS Dialogues Clin Neurosci. 2004;6:39-51.