Neuropsychological functioning in major depression and responsiveness to selective serotonin reuptake inhibitors antidepressants

Abstract 

Background: Only two thirds of patients with major depression (MD) respond to antidepressants. Thus, far applicable predictors of responsiveness to selective serotonergic reuptake inhibitors (SSRIs) have not been found. Cumulative evidence linking serotonergic depletion and cognition led us to hypothesize that the neuropsychological functioning of major depression patients may predict their responsiveness to SSRI antidepressants. Methods: Fifty-five patients meeting DSM-IV criteria for major depression and strict inclusion and exclusion criteria underwent an extensive clinical and neuropsychological assessment prior to the initiation of selective serotonergic treatment. Following 6 weeks of treatment, severity of depression was reassessed, yielding a responsiveness score by which classification of each subject as a responder or nonresponder was made. The study was double blind. Results: Logistic regression yielded neuropsychological indices, which significantly predicted the probability of depressed patients to respond favorably to SSRIs. Responders were characterized by better functioning in “simple” tasks and by worse functioning in “complex” tasks compared to nonresponders. No differences were found for more lateralized right or left hemisphere functions between responders and nonresponders. Limitations: Drug treatment comprised of SSRIs but was not standardized. Responsiveness was assessed following 6 weeks of treatment providing for initial amelioration rather than full remission. Placebo response was not controlled for. These limitations may influence the interpretation of the findings. Conclusions: The present findings suggest that responders and nonresponders to SSRIs might be distinguished by their neuropsychological functioning before treatment. If our findings are replicated, more efficient treatment might be practiced.

Keywords:  Serotonin, Major depression, Neuropsychological assessment, Prediction of treatment responsiveness