A single blind comparison of lithium and lamotrigine for the treatment of bipolar II depression.

BACKGROUND: Treatment studies are lacking for patients with bipolar II disorder (BDII). The objective of this study was to compare lamotrigine (LTG) and lithium (Li) monotherapy for the treatment of BDII depression. METHODS: Patients with BDII acute depression were randomized to open-label monotherapy with LTG or Li, and evaluated by trained raters blinded to treatment. Patients were titrated to 200 mg/day of LTG over 8 weeks or at least 900 mg/day of Li over 2 weeks (serum level 0.6-1.2 mEq/L), and seen biweekly for 16 weeks. The primary outcome variable was change in the Hamilton Depression Rating Scale 17-item (Ham-D(17)), evaluated using mixed effects random regression. RESULTS: Both groups showed significant improvement from baseline to endpoint on the Ham-D(17) (p<0.0001), with no between group differences (p=0.95). Seventy-two percent of the population was rapid cycling by DSM-IV criteria. No differences in response were noted between rapid cyclers and non-rapid cyclers. Early termination for any cause was 42%. The Li group reported significantly more side effects, although drop-out due to side effects did not differ between groups. LIMITATIONS: This study was limited by an open treatment design, a lack of placebo arm, and uneven treatment groups. CONCLUSIONS: Lamotrigine and lithium were effective monotherapy for BDII depression, with comparable response and remission rates. Naturalistic design and lack of placebo limit conclusions, though patient history indicated long standing depression unlikely to be alleviated by time. Patients who received Li reported more side effects, but this did not appear to impact drop-out rates.

Vagus nerve stimulation therapy in a patient with treatment-resistant depression: a case report of long-term follow-up and battery end-of-service.

This is the first case report of a patient who received long-term (69-month) adjunctive vagus nerve stimulation (VNS) therapy for treatment-resistant depression (TRD) and reached VNS battery end-of-service (EOS). The patient is a 41-year-old female with depression who entered a study of adjunctive VNS therapy for TRD. Her Hamilton Rating Scale for Depression (HAM-D) scores dropped from a mean of 33.5 (pre-implantation baseline period) to 16 at the end of the 12-week acute-phase treatment period, and then fluctuated from <7 (normal range) to scores in the moderately depressed range (approximately 20) during long-term follow-up. Three and one-half years after VNS implantation, the patient's HAM-D scores began to increase from a score of 18 to a peak score of 27 approximately 16 months later (5-years post-implantation). The patient subsequently reported that she could no longer feel stimulation from the device and device interrogation 2 weeks later indicated battery EOS. The patient was hospitalized due to worsened depression, the pulse generator was replaced, and medication adjusted. HAM-D scores through the subsequent 9 months of follow-up returned to a pattern of fluctuations within the range noted during the long-term follow-up period prior to VNS battery EOS.

A double-blind, placebo-controlled study of the omega-3 fatty acid docosahexaenoic acid in the treatment of major depression.

OBJECTIVE: This study was an evaluation of the omega-3 fatty acid docosahexaenoic acid (DHA) for the treatment of major depression. METHOD: Thirty-six depressed patients were randomly assigned to receive DHA, 2 g/day, or placebo for 6 weeks. Response was defined a priori as a > or =50% reduction in the score on the Montgomery-Asberg Depression Rating Scale. Thirty-five participants were evaluable; 18 received DHA, and 17 received placebo. RESULTS: Response rates were 27.8% in the DHA group and 23.5% in the placebo group. The difference in response rates between groups did not reach statistical significance. CONCLUSIONS: This trial failed to show a significant effect of DHA monotherapy in subjects with major depression.

Olanzapine in the treatment of apathy in previously depressed participants maintained with selective serotonin reuptake inhibitors: an open-label, flexible-dose study.

BACKGROUND: We report a clinical trial of olanzapine in the treatment of prominent apathy in the absence of depression in patients on long-term treatment with selective serotonin reuptake inhibitors (SSRIs) for nonpsychotic major depression. METHOD: Participants were 21 men and women who met DSM-IV criteria for major depressive disorder in full remission (Montgomery-Asberg Depression Rating Scale [MADRS] score < or = 12) who had been taking an SSRI for at least 3 months. Data are presented (last observation carried forward) based on 20 enrolled participants who completed at least 1 follow-up visit. Participants had significant symptoms of apathy, defined as a Clinical Global Impressions-Severity of Illness scale (CGI-S) score > or = 3, an Apathy Evaluation Scale (AES) score > 30, and a MADRS item 8 (inability to feel) score > or = 2. Participants with a personal or family history of psychosis were excluded. Olanzapine was titrated in 2.5-mg increments at weekly intervals, until CGI-S score improved > or = 2 points from baseline or > or = 1 point with dose-limiting side effects, and participants continued in the protocol for 8 weeks at a stable dose following this improvement. RESULTS: Improvement was clinically evident and demonstrable on all symptom assessments: AES (mean +/- SD change in score = -21.3 +/- 8.7; p < .0001), CGI-S (-2.7 +/- 0.9; p < .0001), MADRS (-5.6 +/- 5.9; p = .001), and MADRS item 8 (-2.2 +/- 1.4; p < .0001). The mean dose of olanzapine was 5.4 +/- 2.8 mg/day. CONCLUSION: These preliminary data suggest that olanzapine may be effective in treating apathy syndrome in nonpsychotic patients taking SSRIs.

A 1-year pilot study of vagus nerve stimulation in treatment-resistant rapid-cycling bipolar disorder.

OBJECTIVE: Vagus nerve stimulation (VNS) appears to be an effective treatment option for patients with treatment-resistant unipolar and bipolar depression. The aim of the present study was to investigate the efficacy of VNS in a group of patients with treatment-resistant rapid-cycling bipolar disorder (RCBD) who were excluded from previous trials. METHOD: Nine outpatients with a DSM-IV-TR diagnosis of treatment-resistant RCBD were treated for 40 weeks with open-label VNS. The first patient was enrolled in June 2001, and the last patient completed the study in July 2005. Patients recorded their depression and mania mood symptoms on a daily basis throughout the study using the National Institute of Mental Health prospective life charting methodology and daily mood ratings. Patients were assessed every 2 weeks during the 2-month baseline period before device activation, every 2 weeks for the remaining 40 weeks of the study, and at the end of the study with the 24-item Hamilton Rating Scale for Depression (HAM-D-24), the 10-item Montgomery-Asberg Depression Rating Scale (MADRS), the Young Mania Rating Scale (YMRS), the Clinical Global Impressions (CGI) scale, the Global Assessment of Functioning (GAF) scale, and the 30-item Inventory of Depressive Symptomatology Self-Report (IDS-SR-30). Any adverse events or device complications were also recorded at each visit. The prospective life charts were analyzed by calculating the area under the curve. Statistical analysis was performed with a mixed-model repeated-measures regression analysis for repeated measures of the various rating scales. Significant p values were < or = .05. RESULTS: Over the 12-month study period, VNS was associated with a 38.1% mean improvement in overall illness as compared to baseline (p = .012), as well as significant reductions in symptoms as measured by the HAM-D-24 (p = .043), MADRS (p = .003), CGI (p = .013), and GAF (p < .001) rating scales. Common adverse events were voice alteration during stimulation and hoarseness. CONCLUSION: These data suggest that VNS may be an efficacious and well-tolerated treatment option for patients with treatment-resistant RCBD. Currently, no comparison is available in the literature. Larger randomized trials are needed to verify these findings.

Prospective predictors of suicide and suicide attempts in 1,556 patients with bipolar disorders followed for up to 2 years.

OBJECTIVES: Bipolar disorders are associated with high rates of suicide attempts (SAs) and completions. Several factors have been reported to be associated with suicide in persons with bipolar disorder, but most studies to date have been retrospective and have not utilized multivariate statistics to account for the redundant prediction among variables submitted for analysis. METHODS: This study examined the association between baseline clinical and demographic variables and subsequent SAs and completions through 2 years of follow-up of participants in the Systematic Treatment Enhancement Program for Bipolar Disorder using a pattern-mixture model. RESULTS: Of the sample with complete data (n = 1,556), 57 patients (3.66%) experienced an SA or completion (CS). Several variables predicted suicidality (SA + CS) in this data set when considered alone, but after controlling for redundant prediction from other baseline characteristics, only history of suicide [odds ratio (OR) = 4.52, p < 0.0001] and percent days depressed in the past year (OR = 1.16, p = 0.036) were significantly associated with SAs and completions. A secondary analysis included a greater number of variables but a smaller sample size (n = 1,014). In the secondary analyses, only prior SAs predicted prospective suicidality (OR = 3.87, p = 0.0029). CONCLUSIONS: These results indicate that patients with bipolar disorder who present with a history of SAs are over four times as likely to have a subsequent SA or completion. Further studies are needed to evaluate and prevent future attempts in this high-risk cohort.

Omega-3 fatty acids for the prevention of postpartum depression: negative data from a preliminary, open-label pilot study.

Based on the putative relationship between depleted omega-3 fatty acids and postpartum depression, we initiated an open-label pilot study of omega-3 fatty acid supplementation with the aim of preventing postpartum depression. Euthymic pregnant females with a past history of depression in the postpartum period were started on 2960 mg of fish oil (1.4:1 eicosapentaenoic acid:docosahexaenoic acid) per day between the 34th to 36th week of pregnancy and assessed through 12 weeks postpartum. Four of seven participants had a depressive episode during the study period. No participants withdrew from the study due to adverse events. This preliminary, small, open-label pilot study failed to show promising results for the use of omega-3 fatty acid monotherapy beginning at 34 to 36 weeks gestation for the prevention of postpartum depression in patients with a prior postpartum depression history. Controlled studies are lacking.