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.).

Longitudinal changes of right ventricular deformation mechanics during trastuzumab therapy in breast cancer patients.

BACKGROUND: Trastuzumab improves dramatically the prognosis of HER2-positive breast cancer patients, but it may lead to cardiotoxicity with left ventricular (LV) systolic dysfunction. Its effects on right ventricular (RV) function have not however been elucidated. We sought to assess LV and RV deformation mechanics during treatment with trastuzumab in breast cancer patients. METHODS AND RESULTS: We studied 101 consecutive women (mean age 54.3 ± 11.4 years) receiving trastuzumab for 12 months; 62 of them (61.4%) had previously received anthracyclines and 26 (25.7%) were receiving taxanes concurrently with trastuzumab. Comprehensive two-dimensional echocardiography with speckle tracking imaging of LV and RV global longitudinal strain (GLS) and RV free wall longitudinal strain (FWLS) analyses were performed at baseline and every 3 months up to treatment completion. Cardiotoxicity was defined as a decrease of baseline LV ejection fraction > 10 percentage units to a value < 50%. At 3 months, only LV GLS was significantly reduced (-19.5 ± 2.7 to -18.7 ± 2.8, P = 0.0410), while at 6 months, LV GLS, RV GLS and RV FWLS had significantly declined reaching their lowest values (-17.9 ± 6.1, P = 0.002, -19.6 ± 5.2, P = 0.003 and -19.7 ± 5.6, P = 0.004, respectively). Ten women (9.9%) developed cardiotoxicity. A RV GLS percent change of -14.8% predicted cardiotoxicity with 66.7% sensitivity and 70.8% specificity (area under the curve 0.68, 95% confidence interval 0.54-0.81), classifying correctly 90% of women with cardiotoxicity. This cut-off is quite similar to the 15% change of LV GLS previously suggested as predictive of cardiotoxicity. CONCLUSIONS: Deformation mechanics of both the left and right ventricle follow similar temporal pattern and degree of impairment during trastuzumab therapy, confirming the global and uniform effect of trastuzumab on myocardial function.