Subcallosal cingulate deep brain stimulation for treatment-resistant unipolar and bipolar depression.

CONTEXT: Deep brain stimulation (DBS) may be an effective intervention for treatment-resistant depression (TRD), but available data are limited. OBJECTIVE: To assess the efficacy and safety of subcallosal cingulate DBS in patients with TRD with either major depressive disorder (MDD) or bipolar II disorder (BP). DESIGN: Open-label trial with a sham lead-in phase. SETTING: Academic medical center. Patients  Men and women aged 18 to 70 years with a moderate-to-severe major depressive episode after at least 4 adequate antidepressant treatments. Ten patients with MDD and 7 with BP were enrolled from a total of 323 patients screened. Intervention  Deep brain stimulation electrodes were implanted bilaterally in the subcallosal cingulate white matter. Patients received single-blind sham stimulation for 4 weeks followed by active stimulation for 24 weeks. Patients then entered a single-blind discontinuation phase; this phase was stopped after the first 3 patients because of ethical concerns. Patients were evaluated for up to 2 years after the onset of active stimulation. MAIN OUTCOME MEASURES: Change in depression severity and functioning over time, and response and remission rates after 24 weeks were the primary efficacy end points; secondary efficacy end points were 1 year and 2 years of active stimulation. RESULTS: A significant decrease in depression and increase in function were associated with chronic stimulation. Remission and response were seen in 3 patients (18%) and 7 (41%) after 24 weeks (n = 17), 5 (36%) and 5 (36%) after 1 year (n = 14), and 7 (58%) and 11 (92%) after 2 years (n = 12) of active stimulation. No patient achieving remission experienced a spontaneous relapse. Efficacy was similar for patients with MDD and those with BP. Chronic DBS was safe and well tolerated, and no hypomanic or manic episodes occurred. A modest sham stimulation effect was found, likely due to a decrease in depression after the surgical intervention but prior to entering the sham phase. CONCLUSIONS: The findings of this study support the long-term safety and antidepressant efficacy of subcallosal cingulate DBS for TRD and suggest equivalent safety and efficacy for TRD in patients with BP. Trial Registration  clinicaltrials.gov Identifier: NCT00367003.

A double blind, placebo-controlled pilot study of galantamine augmentation of antidepressant treatment in older adults with major depression.

OBJECTIVE: Depression in older adults is often associated with cognitive abnormalities and may predict later development of a primary cognitive disorder. This double-blind, randomized, placebo-controlled pilot study was designed to assess the safety and efficacy of galantamine augmentation of antidepressant treatment for depressive and cognitive symptoms in older adults with major depression. METHODS: Thirty-eight, non-demented older adults (age >50) with major depression were randomized to receive galantamine or placebo augmentation of standard antidepressant pharmacotherapy (venlafaxine XR or citalopram). Mood and cognitive status were monitored for 24 weeks using the 24-item Hamilton Rating Scale for Depression and the Repeatable Battery for the Assessment of Neuropsychological Status. RESULTS: Both groups showed significant improvements in mood and cognition over 24 weeks, but no significant difference was found in change over time between groups. An exploratory post-hoc analysis suggested that patients randomized to galantamine had lower depression scores compared to patients in the placebo group after 2 weeks of treatment. Dropout was high with more subjects randomized to antidepressant plus galantamine withdrawing early from the study. CONCLUSIONS: This pilot study failed to demonstrate a benefit for galantamine augmentation of antidepressant medication in the treatment of depression in older adults. Future studies should explore strategies for reducing dropout in such longitudinal trials and more carefully assess time to response with cholinesterase inhibitor augmentation.