Jiri Kozeny

Amygdala volumes in mood disorders — Meta-analysis of magnetic resonance volumetry studies

BACKGROUND The amygdala plays an important role in the regulation of emotions and has been implicated in the pathophysiology of mood disorders. Studies of amygdala volumes in mood disorders have been conflicting, with findings of increased, decreased and unchanged amygdala volumes in patients relative to controls. We present the largest meta-analysis of amygdala volumes in mood disorders and the first one to investigate modifying effects of clinical, demographic and methodological variables. METHODS We reviewed 40 magnetic resonance imaging studies investigating amygdala volumes in patients with unipolar or bipolar disorders. For meta-analysis we used standardized differences in means (SDM) and random effect models. In the search for sources of heterogeneity, we subdivided the studies based on diagnosis, setting, age, medication status, sex, duration of illness, slice thickness, interrater reliability of tracing and anatomical definitions used. RESULTS The volumes of the left and right amygdala in bipolar (N=215) or unipolar (N=409) patients were comparable to controls. Bipolar children and adolescents had significantly smaller left amygdala volumes relative to controls (SDM=-0.34, 95%CI=-0.65; -0.04, z=-2.20, p=0.03), whereas bipolar adults showed a trend for left amygdala volume increases (SDM=0.46, 95%CI=-0.03; 0.96, z=1.83, p=0.07). Unipolar inpatients had significantly larger left (SDM=0.35, 95%CI=0.03; 0.67, z=-2.17, p=0.03) amygdala volumes than controls, with no significant amygdala volume changes in unipolar outpatients. LIMITATIONS Heterogeneity of included studies. CONCLUSIONS The absence of overall differences in amygdala volumes, in the presence of significant and sometimes mirror changes in patient subgroups, demonstrates marked heterogeneity among mood disorders. Amygdala volume abnormalities may not be associated with mood disorders per se, but rather may underlie only some dimensions of illness or represent artifacts of medication or comorbid conditions.

Low frequency (1-Hz), right prefrontal repetitive transcranial magnetic stimulation (rTMS) compared with venlafaxine ER in the treatment of resistant depression: a double-blind, single-centre, randomized study.

BACKGROUND Previous studies have shown effectiveness of repetitive transcranial magnetic stimulation (rTMS) in the treatment of depression. This double-blind study compared efficacy of l Hz rTMS over the right prefrontal dorsolateral cortex with venlafaxine ER in the treatment of resistant depression. METHODS A total of 60 inpatients with depressive disorder (DSM-IV criteria), who previously did not respond to at least one antidepressant treatment, were randomly assigned to 1 Hz rTMS with placebo and venlafaxine ER with sham rTMS for 4 weeks. The primary outcome measure was score change in the Montgomery-Asberg Depression Rating Scale (MADRS). We also used Clinical Global Impression (CGI) and Beck Depressive. Inventory-Short Form (BDI-SF). The response was defined as a >or=50% reduction of MADRS score. RESULTS There were no significant differences between treatment groups in MADRS (p=0.38), BDI-SF (p=0.56) and CGI (p=0.17) scores from baseline to endpoint. Response rates for rTMS (33%) and venlafaxine (39%) as well as remission (MADRS score<or=10 points) rates (19% vs. 23%) and drop-out rate did not differ between treatment groups. There were significant reductions of MADRS, CGI and BDI-SF scores in both groups. LIMITATIONS Small sample size. No placebo arm was included for ethical reasons, because both treatments have previously been reported to be more effective than placebo. Relatively short duration of antidepressant treatment. CONCLUSION The findings of this study suggest that, at least in the acute treatment, the right sided rTMS produces clinically relevant reduction of depressive symptomatology in patients with resistant depression comparable to venlafaxine ER. Larger sample sizes are required to confirm these results.

The early improvement of depressive symptoms as a potential predictor of response to antidepressants in depressive patients who failed to respond to previous antidepressant treatments. Analysis of naturalistic data.

INTRODUCTION Current studies suggest that improvement of depressive symptoms after 2 weeks of treatment could predict the subsequent response. The aim of our study was to compare the predictive effect of early improvement (EI) after 1 and 2 weeks of treatment in patients who had failed to respond to previous antidepressant treatments (≥1 unsuccessful antidepressant trial). METHOD Seventy-one subjects were treated (≥4 weeks) with various antidepressants chosen according to the judgment of attending psychiatrists. We used three definitions of EI (MADRS reduction ≥20, 25, 30%) at both time points. Areas under curve (AUC) were calculated to compare predictive effect of EI. RESULTS We found lower MADRS scores in weeks 1 and 2 in responders (≥50% reduction of MADRS, n=35) compared to nonresponders. AUCs of MADRS reduction for response prediction at week 1 and 2 were not significantly different (0.73 vs 0.8; p=0.24). CONCLUSION The results indicate that improvement of depressive symptoms in the treatment of resistant patients may occur after the first week of treatment. The predictive potential might be comparable to that found after the second week of antidepressant intervention and be clinically meaningful.

Antidepressant monotherapy compared with combinations of antidepressants in the treatment of resistant depressive patients: A randomized, open-label study

Abstract Objective. This randomized, 6-week, open-label study compared efficacy of CAD and antidepressant monotherapies (ADM) that had been chosen according to clinical judgment of the attending psychiatrist. Methods. A total of 60 inpatients (intent-to-treat analysis) with depressive disorder (≥ 1 unsuccessful antidepressant treatment) were randomly assigned to the interventions. The responders who completed the acute phase of study, were evaluated for relapse within 2 months of follow-up treatment. The primary outcome measure was change in the Montgomery–Åsberg Depression Rating Scale (MADRS) and response was defined as a ≥ 50% reduction of MADRS score. Results. Mean changes in total MADRS score from baseline to week 6 for patients in both treatment modalities were not different (ADM = 13.2 ± 8.6 points; CAD = 14.5 ± 9.5 points; P = 0.58). The analysis of covariance performed for significantly higher value of imipramine equivalent dose in CAD group showed only a non-significant between-group difference for total MADRS change (P = 0.17). There were also no differences between groups in response rate (ADM = 48%; CAD = 58%) and number of drop-outs in acute treatment as well as proportion of responders’ relapses in the follow-up. Conclusion. Both treatment modalities produced clinically relevant reduction of depressive symptomatology in acute treatment of patients with resistant depression and their effect was comparable.