Duration of Adjunctive Antidepressant Maintenance in Bipolar I Depression.

BACKGROUND: Antidepressants are used to treat acute depression in patients with bipolar I disorder, but their effect as maintenance treatment after the remission of depression has not been well studied. METHODS: We conducted a multisite, double-blind, randomized, placebo-controlled trial of maintenance of treatment with adjunctive escitalopram or bupropion XL as compared with discontinuation of antidepressant therapy in patients with bipolar I disorder who had recently had remission of a depressive episode. Patients were randomly assigned in a 1:1 ratio to continue treatment with antidepressants for 52 weeks after remission or to switch to placebo at 8 weeks. The primary outcome, assessed in a time-to-event analysis, was any mood episode, as defined by scores on scales measuring symptoms of hypomania or mania, depression, suicidality, and mood-episode severity; additional treatment or hospitalization for mood symptoms; or attempted or completed suicide. Key secondary outcomes included the time to an episode of mania or hypomania or depression. RESULTS: Of 209 patients with bipolar I disorder who participated in an open-label treatment phase, 150 who had remission of depression were enrolled in the double-blind phase in addition to 27 patients who were enrolled directly. A total of 90 patients were assigned to continue treatment with the prescribed antidepressant for 52 weeks (52-week group) and 87 were assigned to switch to placebo at 8 weeks (8-week group). The trial was stopped before full recruitment was reached owing to slow recruitment and funding limitations. At 52 weeks, 28 of the patients in the 52-week group (31%) and 40 in the 8-week group (46%) had a primary-outcome event. The hazard ratio for time to any mood episode in the 52-week group relative to the 8-week group was 0.68 (95% confidence interval [CI], 0.43 to 1.10; P = 0.12 by log-rank test). A total of 11 patients in the 52-week group (12%) as compared with 5 patients in the 8-week group (6%) had mania or hypomania (hazard ratio, 2.28; 95% CI, 0.86 to 6.08), and 15 patients (17%) as compared with 35 patients (40%) had recurrence of depression (hazard ratio, 0.43; 95% CI, 0.25 to 0.75). The incidence of adverse events was similar in the two groups. CONCLUSIONS: In a trial involving patients with bipolar I disorder and a recently remitted depressive episode, adjunctive treatment with escitalopram or bupropion XL that continued for 52 weeks did not show a significant benefit as compared with treatment for 8 weeks in preventing relapse of any mood episode. The trial was stopped early owing to slow recruitment and funding limitations. (Funded by the Canadian Institutes of Health Research; ClinicalTrials.gov number, NCT00958633.).

Melancholic Versus Non-Melancholic Depression: a Prospective Study.

BACKGROUND: The binarian model views melancholia as a distinct depressive class, whereas the unitarian model views it as a more severe expression of depression. This study aims to investigate the sociodemographic, clinical, and course differences between melancholic and non-melancholic depression. METHODS: This prospective observational study was carried out at Kasturba Hospital, Manipal, India from November 2010 to September 2011. We recruited consecutive inpatients aged 18 to 60 years who have a diagnosis of depressive disorder (based on ICD-10), with or without any psychiatric or physical comorbidities. Patients were categorised into melancholia and non-melancholia using the CORE questionnaire, with scores of ≥8 indicating the presence of melancholic depression. In addition, patients were evaluated using the Hamilton Depression Rating Scale, Hamilton Anxiety Rating Scale, Somatoform Symptom Checklist, Columbia Suicide Severity Rating Scale, Clinical Global Impression, and Presumptive Stressful Life Events Scale at baseline and at 1, 3, and 6 months. RESULTS: Of 87 inpatients with a diagnosis of depression, 50 met the inclusion criteria and 37 were excluded. Compared with patients with non-melancholic depression, patients with melancholic depression had higher depression score (30.8 vs 23.8, p < 0.001), had higher number of patients with psychotic depression (39.1% vs 7.4%, p = 0.007), had higher overall illness severity score (5.9 vs 4.8, p < 0.001), and had higher number of patients with suicidal ideation and suicidal behaviour. Regarding the course of melancholia, the number of melancholic patients decreased from 23 at baseline to eight at 1 month, three at 3 months, and three at 6 months. Scores of non-interactiveness, retardation, and agitation decrease significantly over 3 months. CONCLUSIONS: The construct and course of melancholia may be viewed as a part of depression, more in line with severe depression. Melancholia increases the risk for suicidal ideation and suicidal behaviour.