Risk of switch in mood polarity to hypomania or mania in patients with bipolar depression during acute and continuation trials of venlafaxine, sertraline, and Bupropion as adjuncts to mood stabilizers
ABSTRACT The authors examined the comparative risks of switches in mood polarity into hypomania or mania during acute and continuation trials of adjunctive antidepressant treatment of bipolar depression.
One hundred fifty-nine patients with bipolar I disorder or bipolar II disorder participated in a total of 228 acute (10-week) randomized trials of bupropion, sertraline, or venlafaxine as an adjunct to a mood stabilizer. Patients in 87 of these trials entered continuation treatment for up to 1 year. Antidepressant response and the occurrence of subthreshold brief hypomania (emergence of brief hypomania [at least 1 but <7 days] or recurrent brief hypomania) and threshold switches (emergence of full-duration hypomania [> or =7 days] or mania) were blindly assessed by using clinician-rated daily reports of mood-associated dysfunction on the National Institute of Mental Health Life Chart Method.
Threshold switches into full-duration hypomania and mania occurred in 11.4% and 7.9%, respectively, of the acute treatment trials and in 21.8% and 14.9%, respectively, of the continuation trials. The rate of threshold switches was higher in the 169 trials in patients with bipolar I disorder (30.8%) than the 59 trials in patients with bipolar II disorder (18.6%). The ratio of threshold switches to subthreshold brief hypomanias was higher in both the acute (ratio=3.60) and continuation trials (ratio=3.75) of venlafaxine than in the acute and continuation trials of bupropion (ratios=0.85 and 1.17, respectively) and sertraline (ratios=1.67 and 1.66, respectively). In only 37 (16.2%) of the original 228 acute antidepressant trials, or in only 23.3% of the patients, was there a sustained antidepressant response in the continuation phase in the absence of a threshold switch.
Adjunctive treatment with antidepressants in bipolar depression was associated with substantial risks of threshold switches to full-duration hypomania or mania in both acute and long-term continuation treatment. Of the three antidepressants included in the study, venlafaxine was associated with the highest relative risk of such switching and bupropion with the lowest risk.
[Show abstract] [Hide abstract]
ABSTRACT: Background: To evaluate the effectiveness of quetiapine extended release once daily in bipolar depression. Methods: Double-blind, placebo-controlled study in acutely depressed adults with bipolar For If disorder, with or without rapid cycling. Patients were randomized to 8 weeks of quetiapine extended release (XR) 300 mg daily monotherapy or placebo. The primary outcome measure was changed from baseline to Week 8 in MADRS total score. Results: Quetiapine XR 300 mg once daily (N=133) showed significantly greater improvement in depressive symptoms compared with placebo (N=137) from Week 1 (p < 0.001) through to Week 8 (p < 0.001). Mean change in MADRS total score at Week 8 was 17.4 in the quetiapine XR group and -11.9 in the placebo group (p<0.001). Response (>= 50% reduction in MADRS total score) and remission (MADRS total score <= 12) rates at Week 8 were significantly higher with quetiapine XR compared with placebo (p <0001 and p < 0.05, respectively). Quetiapine XR improved core symptoms of depression. The most common adverse events associated with quetiapine XR were dry mouth, somnolence, and sedation. Greater weight gain was observed in patients on quetiapine XR relative to placebo. Limitations: Fewer patients with bipolar II disorder included, only one fixed dose tested and the lack of an active comparator. Conclusions: Quetiapine XR (300 mg) once daily monotherapy was signiticantly more effective than placebo for treating episodes of depression in bipolar l disorder, throughout the 8-week study, with significance observed as early as Day 7. Adverse events were consistent with the known effects of queliapine. Published by Elsevier B.V.Journal of Affective Disorders 10/2014; 168:485-493. DOI:10.1016/j.jad.2014.07.007 · 3.71 Impact Factor
[Show abstract] [Hide abstract]
ABSTRACT: The severity of bipolar disorder can be assessed using the daily prospective National Institute of Mental Health׳s Life Chart Method (LCM-p). Also for scientific research the LCM-p, has been used frequently. However, processing and analyzing the LCM-p for research purposes, are challenging because of the multitude of complex measures that can be derived from the data. In the current paper we review the different LCM-p course variables (mood episodes, average severity, proportion of time ill and mood switches) and their definitions. Strengths and limitations and the impact of the use of different LCM-p course measures and definitions on the research results are described. A systematic review of original papers on the LCM was conducted using 9 electronic databases for literature between January 1996 and December 2014. Papers using other prospective charting procedures were not evaluated in the current study. The initial literature search led to 1352 papers of which 21 were eventually selected. A relatively wide variety of definitions of LCM-p course variables was used across the studies. Especially for the calculation of number of episodes and mood switch no univocal definition seems to exist. Across studies several different durations and severity criteria are applied to calculate these variables. We describe which variables and definitions are most suitable for detecting specific bipolar disease course characteristics and patterns. In the absence of a golden standard for the calculation of LCM-p course variables, researchers should report the exact method they applied to their LCM-p data, and clearly motivate why this is their method of first choice considering their research aim. Copyright © 2015 Elsevier B.V. All rights reserved.Journal of Affective Disorders 01/2015; 175C:260-268. DOI:10.1016/j.jad.2015.01.005 · 3.76 Impact Factor