Sleep architecture and cognitive changes in olanzapine-treated patients with depression: a double blind randomized placebo controlled trial.

BACKGROUND: Disturbance in sleep quality is a symptom of Major Depressive Disorder (MDD) and Bipolar Disorder (BD) and thus improving quality of sleep is an important aspect of successful treatment. Here, a prospective, double-blind, randomized, placebo-controlled study examined the effect of olanzapine (an atypical antipsychotic) augmentation therapy on sleep architecture, specifically slow wave sleep (SWS), in the treatment of depression. The effect of olanzapine augmentation therapy on other features of sleep (e.g., sleep continuity) and depression (e.g., illness severity and cognitive function) were also determined. METHODS: Patients currently experiencing a major depressive episode and who were on a stable medication were included. Sleep architecture was measured by overnight ambulatory polysomnography. Illness severity was determined using the Montgomery-Asberg Depression Rating Scale (MADRS). Cognitive function was examined using Cambridge Neuropsychological Test Automated Battery (CANTAB): Spatial Working Memory (SWM), Spatial Span (SSP), and Reaction Time (RTI) tasks. Polysomnographs, clinical measures and cognitive tests were administered at baseline, after 2-4 days of treatment and after 28-31 days of treatment. Twenty-five patients participated in the study (N = 10, N = 15 for placebo and olanzapine treated groups respectively). RESULTS: The primary objective of the study was to assess the objective (polysomnographic) changes in sleep quality, defined as changes in SWS, following olanzapine treatment for depression. Latency to but not duration of SWS was found to significantly differ between olanzapine- and placebo-treated participants (Hedge's g: 0.97, 0.13 respectively). A significant improvement in olanzapine-treated participants over placebo-treated participants was observed in secondary outcome measures, including sleep efficiency, total sleep time, and sleep latency. Secondary objectives assessed the subjective changes in sleep quality parameters and correlated them with measures of illness severity and changes in cognition. MADRS scores were significantly improved in olanzapine-treated participants over time but not more than placebo treatment. There was no significant difference between olanzapine- and placebo-treated participants in SWM, SSP or RTI tasks. CONCLUSIONS: Olanzapine augmentation treatment generally did not improve SWS but did improve sleep continuity and depression. Olanzapine may be one of few medications that improve sleep continuity, thus directly targeting symptoms of depression. TRIAL REGISTRATION: ClinicalTrials.gov, NCT00520507.

Effects of electroconvulsive therapy and repetitive transcranial magnetic stimulation on serum brain-derived neurotrophic factor levels in patients with depression.

OBJECTIVE: Brain-derived neurotrophic factor (BDNF) levels are decreased in individuals with depression and increase following antidepressant treatment. The objective of this study is to compare pre- and post-treatment serum BDNF levels in patients with drug-resistant major depressive disorder (MDD) who received either electroconvulsive therapy (ECT) or repetitive transcranial magnetic stimulation (rTMS). It is hypothesized that non-pharmacological treatments also increase serum BDNF levels. METHODS: This was a prospective, single-blind study comparing pre- and post-treatment serum BDNF levels of 29 patients with drug-resistant MDD who received ECT or rTMS treatment. Serum BDNF levels were measured 1 week prior to and 1 week after treatment using the sandwich ELISA technique. Depression severity was measured 1 week before and 1 week after treatment using the Hamilton Depression Rating Scale. Two-sided normal distribution paired t-test analysis was used to compare pre- and post-treatment BDNF concentration and illness severity. Bivariate correlations using Pearson's coefficient assessed the relationship between post-treatment BDNF levels and post-treatment depression severity. RESULTS: There was no significant difference in serum BDNF levels before and after ECT, although concentrations tended to increase from a baseline mean of 9.95-12.29 ng/ml after treatment (p = 0.137). Treatment with rTMS did not significantly alter BDNF concentrations (p = 0.282). Depression severity significantly decreased following both ECT (p = 0.003) and rTMS (p < 0.001). Post-treatment BDNF concentration was not significantly correlated with post-treatment depression severity in patients who received either ECT (r = -0.133, p = 0.697) or rTMS (r = 0.374, p = 0.126). It is important to note that these results are based on the small number of patients included in this study. CONCLUSION: This study suggests that ECT and rTMS may not exert their clinical effects by altering serum BDNF levels in patients with drug-resistant MDD. Serum BDNF concentration may not be a biomarker of ECT or rTMS treatment response.

Repetitive transcranial magnetic stimulation for treatment of elderly patients with depression - an open label trial.

BACKGROUND: RTMS has been developed as a novel tool for treating depression but the clinical significance of this treatment has been variable, especially in the older depressed subjects. METHODS: Medication-resistant depressed patients 60 years or older were treated for two weeks (10 sessions) with high-frequency rTMS delivered to the left dorsolateral prefrontal cortex at 100% of motor threshold. Each session consisted of 20 trains at 10Hz delivered in 8-second duration. The patients continued taking their psychotropic medications throughout the study. RESULTS: Nineteen of the 20 subjects completed the trial. One subject dropped out after 8 sessions because of discomfort. The average age of our patients was 66.8 years (6 males and 14 females). Six patients responded and there was a 31.6% mean reduction in Hamilton Depression Rating Scale (HDRS) scores from baseline at the end of the treatment. There was statistically significant decrease from baseline in both HDRS and HARS scores at the end of treatment. rTMS was generally well tolerated. CONCLUSION: These preliminary finding suggests that rTMS may be an effective treatment alternative to a subpopulation of medication resistant older depressed patients.