Does prior antidepressant treatment of major depression impact brain function during current treatment?
ABSTRACT The relationship between prior antidepressant treatment and prefrontal brain functional response to subsequent treatment with antidepressant medication or placebo is unknown. Eighty-nine adults with Major Depressive Disorder (MDD), characterized as antidepressant-experienced or antidepressant-naive, received one week of single-blind placebo treatment prior to eight weeks of randomized treatment with medication (fluoxetine or venlafaxine; n=47) or placebo (n=42) in one of three similar placebo-controlled trials. Brain function was assessed at baseline, end of placebo lead-in, and during randomized treatment using quantitative electroencephalography (qEEG). The authors assessed change in prefrontal theta-band cordance (PFC) in antidepressant-experienced vs. antidepressant-naive subjects. Treatment history groups differed significantly on PFC change during the placebo lead-in even when controlling for clinical and demographic variables (F(1,62)=4.27, p=.04). As assessed in linear mixed models that examined treatment history (antidepressant-experienced or antidepressant-naive), treatment assignment (medication or placebo), and their interaction as predictors, treatment history also predicted PFC change during the randomized phase of treatment even when controlling for pretreatment clinical and demographic and symptom improvement during treatment (F(1,5o)=5.20, p=.03). The interaction was not significant. Post hoc analyses showed that antidepressant-experienced subjects treated with placebo showed PFC changes that did not differ from PFC changes seen in the medication group. Results suggest that prefrontal brain functional changes during treatment for MDD may differ depending upon prior treatment with antidepressant medication.
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ABSTRACT: This post hoc analysis aimed to determine whether patients with major depressive disorder (MDD) in duloxetine trials who were antidepressant naive or who were previously exposed to antidepressants exhibited differences in efficacy and functioning. Data were pooled from 15 double-blind, placebo- and/or active-controlled duloxetine trials of adult patients with MDD conducted by Eli Lilly and Company. The individual studies took place between March 2000 and November 2009. Data were analyzed using 4 pretreatment subgroups: first-episode never treated, multiple-episode never treated, treated previously only with selective serotonin reuptake inhibitors (SSRIs), and previously treated with antidepressants other than just SSRIs. Measures included the 17-item Hamilton Depression Rating Scale (HDRS-17) total and somatic symptom subscale scores, Montgomery-Asberg Depression Rating Scale (MADRS) total score, and Sheehan Disability Scale total score. Response rates (50% and 30%) were based on the HDRS-17 total score and remission rates on either the HDRS-17 or MADRS total score. Response and remission rates were significantly greater (P < .05 in 11 of 12 comparisons) for duloxetine versus placebo in the 4 subgroups. A trend of greater response and remission occurred for first-episode versus multiple-episode patients; both groups were generally higher than the antidepressant-treated groups. Mean changes in efficacy measures were mostly significantly greater (P < .05 in 13 of 16 comparisons) for duloxetine versus placebo within each pretreatment subgroup, with some (P < .05 in 2 of 24 comparisons) significant interaction effects between subgroups on HDRS-17 total and somatic symptoms scores. Duloxetine was generally superior to placebo on response and remission rates and in mean change on efficacy measures. Response and remission rates were numerically greater for first-episode versus multiple-episode and drug-treated patients. Mean change differences on efficacy measures among the 4 subgroups were inconsistent. Duloxetine showed a similar therapeutic effect independent of episode frequency and antidepressant pretreatment.
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ABSTRACT: Brain oscillatory activity from the midline prefrontal region has been shown to reflect brain dysfunction in subjects with Major Depressive Disorder (MDD). It is not known, however, whether electrodes from this area provide unique information about brain function in MDD. We examined a set of midline sites and two other prefrontal locations for detecting cerebral activity differences between subjects with MDD and healthy controls. Resting awake quantitative EEG (qEEG) data were recorded from 168 subjects: 47 never-depressed adults and 121 with a current major depressive episode. Individual midline electrodes (Fpz, Fz, Cz, Pz, and Oz) and prefrontal electrodes outside the hairline (Fp1, Fp2) were examined with absolute and relative power and cordance in the theta band. We found that MDD subjects exhibited higher values of cordance (p=0.0066) at Fpz than controls; no significant differences were found at other locations, and power measures showed trend-level differences. Depressed adults showed higher midline cordance than did never-depressed subjects at the most-anterior midline channel. Salient abnormalities in MDD may be detectable by focusing on the prefrontal midline region, and EEG metrics from focused electrode arrays may offer clinical practicality for clinical monitoring.Journal of Psychiatric Research 06/2014; 53. DOI:10.1016/j.jpsychires.2014.01.018 · 4.09 Impact Factor
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ABSTRACT: Major depressive disorder (MDD) is an emergent cause of personal and socio-economic burden, both for the high prevalence of the disorder and the unsatisfying response rate of the available antidepressant treatments. No reliable predictor of treatment efficacy and tolerance in the single patient is available, thus drug choice is based on a trial and error principle with poor clinical efficiency. Among modulators of treatment outcome, genetic polymorphisms are thought to explain a significant share of the inter-individual variability. The present review collected the main pharmacogenetic findings primarily about antidepressant response and secondly about antidepressant induced side effects, and discussed the main strengths and limits of both candidate and genome-wide association studies and the most promising methodological opportunities and challenges of the field. Despite clinical applications of antidepressant pharmacogenetics are not available yet, previous findings suggest that genotyping may be applied in the clinical practice. In order to reach this objective, further rigorous pharmacogenetic studies (adequate sample size, study of better defined clinical subtypes of MDD, adequate covering of the genetic variability), their combination with the results obtained through complementary methodologies (e.g., pathway analysis, epigenetics, transcriptomics, and proteomics), and finally cost-effectiveness trials are required. © 2013 Wiley Periodicals, Inc.American Journal of Medical Genetics Part B Neuropsychiatric Genetics 09/2013; 162(6). DOI:10.1002/ajmg.b.32184 · 3.27 Impact Factor