Dataset Information

Switching from Inadequate Adjunctive or Combination Treatment Options to Brexpiprazole Adjunctive to Antidepressant: An Open-Label Study on the Effects on Depressive Symptoms and Cognitive and Physical Functioning.

ABSTRACT:

Background

Approximately 50% of patients with major depressive disorder do not respond adequately to their antidepressant treatment, underscoring the need for more effective treatment options. The objective of this study was to investigate the effect of adjunctive brexpiprazole on depressive symptoms in patients with major depressive disorder who were not responding to adjunctive or combination therapy of their current antidepressant treatments with several different classes of agents (NCT02012218).

Methods

In this 6-week, open-label, phase 3b study, patients with major depressive disorder who had an inadequate response to ?1 adjunctive or combination therapy, in addition to history of ?1 failure to monotherapy antidepressant treatment, were switched to adjunctive brexpiprazole. Efficacy was assessed by change from baseline to week 6 in Montgomery-Åsberg Depression Rating Scale total score. Patient functioning was assessed using the Sheehan Disability Scale and the Cognitive and Physical Functioning Questionnaire. Safety and tolerability were also assessed.

Results

A total of 51/61 (83.6%) patients completed 6 weeks of treatment with adjunctive brexpiprazole. Improvements in depressive symptoms were observed (least squares mean change from baseline to week 6 in Montgomery-Åsberg Depression Rating Scale total score, -17.3 [P < .0001]) as well as improvements in general and cognitive functioning (mean changes from baseline to week 6: Sheehan Disability Scale, -3.1 [P < .0001]; Massachusetts General Hospital-Cognitive and Physical Functioning Questionnaire, -9.2 [P < .0001]). The most common adverse event was fatigue (14.8%); akathisia was reported by 8.2% of patients.

Conclusions

In patients with major depressive disorder who had switched to open-label adjunctive brexpiprazole following inadequate response to previous adjunctive or combination therapy, improvements were observed in depressive symptoms, general functioning, cognitive function, and energy/alertness.

SUBMITTER: Fava M

PROVIDER: S-EPMC5412581 | biostudies-literature | 2017 Jan

REPOSITORIES: biostudies-literature

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Publications

Switching from Inadequate Adjunctive or Combination Treatment Options to Brexpiprazole Adjunctive to Antidepressant: An Open-Label Study on the Effects on Depressive Symptoms and Cognitive and Physical Functioning.

Fava Maurizio M Okame Takao T Matsushima Yuki Y Perry Pamela P Weiller Emmanuelle E Baker Ross A RA

The international journal of neuropsychopharmacology 20170101 1

<h4>Background</h4>Approximately 50% of patients with major depressive disorder do not respond adequately to their antidepressant treatment, underscoring the need for more effective treatment options. The objective of this study was to investigate the effect of adjunctive brexpiprazole on depressive symptoms in patients with major depressive disorder who were not responding to adjunctive or combination therapy of their current antidepressant treatments with several different classes of agents (N ...[more]

PMID: 27784751

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Project description:BackgroundThis systematic review and meta-analysis included double-blind, randomized, placebo-controlled trials of brexpiprazole adjunctive treatment (0.5-3 mg/d) for major depressive disorder where antidepressant treatment had failed.MethodsThe outcomes were the response rate (primary), remission rate (secondary), Montgomery Åsberg Depression Rating Scale score (secondary), Sheehan Disability Scale scores (secondary), Clinical Global Impression-Improvement/Severity scores, discontinuation rate, and individual adverse events. A subgroup meta-analysis of the data at week 6 compared outcomes by dose >2 mg/d or ≤2 mg/d (2 mg/d is the recommended dose).ResultsWe identified 9 studies (n = 3391). Compared with placebo, brexpiprazole (any dose) was superior for response rate (risk ratio [RR] = 0.93, 95% confidence interval [95% CI] = 0.89-0.97, number needed to treat = 17), remission rate (RR = 0.95, 95% CI = 0.93-0.98, number needed to treat = 25), Montgomery Åsberg Depression Rating Scale score (standardized mean difference = -0.20, 95% CI = -0.29, -0.11), Sheehan Disability Scale score (standardized mean difference = -0.12, 95% CI = -0.21, -0.04), and Clinical Global Impression-Improvement/Severity scores but was associated with a higher discontinuation rate, akathisia, insomnia, restlessness, somnolence, and weight increase. Doses >2 mg/d had a significantly higher RR for response rate than ≤2 mg/d (0.96 vs 0.89); moreover, compared with placebo, doses >2 mg/d were associated with higher incidences of akathisia (RR = 4.58) and somnolence (RR = 7.56) as well as were marginally associated with a higher incidence of weight increase (RR = 3.14, P = .06). Compared with placebo, doses ≤2 mg/d were associated with higher incidences of akathisia (RR = 2.28) and weight increase (RR = 4.50).ConclusionsBrexpiprazole adjunctive treatment is effective for major depressive disorder when antidepressant treatment fails. At 6 weeks, doses ≤2 mg/d presented a better risk/benefit balance than >2 mg/d.

Project description:To investigate the specific effect of adjunctive aripiprazole on sexual function in patients with major depressive disorder and a history of an inadequate response to antidepressant medication by controlling for improvement in depressive symptoms as measured by improvement in Montgomery-Asberg Depression Rating Scale (MADRS) total scores. For this post hoc analysis, data were pooled from 3 multicenter, randomized, double-blind, placebo-controlled aripiprazole augmentation studies (CN138-139: June 2004-April 2006; CN138-163: September 2004-December 2006; and CN138-165: March 2005-April 2008). Outpatients who met DSM-IV-TR criteria for a major depressive episode that had lasted ≥8 weeks with an inadequate response to prospective antidepressant treatment were randomized to adjunctive aripiprazole or placebo for 6 weeks. Sexual functioning was assessed using the Massachusetts General Hospital Sexual Functioning Inventory (MGH-SFI). To assess whether adjunctive aripiprazole improves sexual functioning directly, rather than as an indirect effect of improvement in depression symptoms, the mean change in MGH-SFI item scores and overall improvement scores was assessed using analysis of covariance, with double-blind baseline and change in MADRS total score as covariates. Correlations between MGH-SFI items and MADRS total score and prolactin levels were also assessed. The analysis included 1,092 subjects (n=737 female and n=355 male). In the total population, adjunctive aripiprazole demonstrated statistically significant greater improvements versus placebo on the MGH-SFI item "interest in sex" (-0.34 vs -0.18, P<.05). In males, no significant treatment differences were observed. In females, improvements in sexual functioning with adjunctive aripiprazole versus placebo were found on the MGH-SFI items "interest in sex" (-0.41 vs -0.21, P<.05) and "sexual satisfaction" (-0.44 vs -0.25, P<.05). Aripiprazole adjunctive to antidepressant treatment can have some beneficial effects on sexual functioning in patients with major depressive disorder who respond inadequately to standard antidepressant treatment; the benefits in women were specific to sexual interest and satisfaction and were independent of the improvement in depressive symptoms. clinicaltrials.gov Identifiers: NCT00095823, NCT00095758, and NCT00105196.

Project description:The neuroactive steroid metabolite of progesterone, allopregnanolone, is a positive allosteric modulator of γ-aminobutyric acid-A (GABAA) receptors and a putative treatment for mood disorders. This pilot study was performed to determine whether an oral allopregnanolone analog (ganaxolone) may be effective adjunctive therapy for persistent depression despite adequate antidepressant treatment in postmenopausal women. Ten postmenopausal women (mean ± SD age: 62.8 ± 6.3 years; range, 53-69 years) with persistent depression despite adequate antidepressant treatment (current DSM-IV-TR major depressive episode per the Structured Clinical Interview for DSM-IV-TR, Montgomery-Asberg Depression Rating Scale [MADRS] score ≥ 16, and treated with an adequately dosed antidepressant for ≥ 6 weeks) were studied from December 2016 to April 2018. Open-label ganaxolone (225 mg twice daily, increased to 450 mg twice daily if tolerated) was administered for 8 weeks, followed by a 2-week taper. Mean ± SEM total MADRS score (primary endpoint) decreased by 8 weeks (24.4 ± 1.6 to 12.8 ± 2.9, P = .015), and the decrease persisted over the 2-week taper (P = .019); of the 9 subjects who completed the full 8-week treatment period, 44% (4/9) experienced response (MADRS score decrease ≥ 50%) and remission (final MADRS score < 10), which persisted in 100% and 50% of subjects at 10 weeks, respectively. Secondary endpoints showed significant improvement, including Inventory of Depressive Symptomatology-Self-Report score (P = .003), MADRS reduced sleep subscale score (P < .001), total Symptoms of Depression Questionnaire (SDQ) score (P = .012), and scores on SDQ subscales for disruptions in sleep quality (P = .003) and changes in appetite and weight (P = .009) over 8 weeks. No significant effects were observed on quality of life or sexual function. All subjects experienced sleepiness and fatigue; 60% experienced dizziness. In this open-label, uncontrolled pilot study, adjunctive ganaxolone appears to exert antidepressant effects but produces sedation with twice-daily dosing. Ganaxolone may also improve sleep, which may be useful in patients with depression and insomnia. ClinicalTrials.gov identifier: NCT02900092.

Project description:ObjectiveEpisodes of major depressive disorder (MDD) characterized by high levels of anxiety symptoms are less likely to respond to some forms of antidepressant treatment (ADT). This report examines the effects of adjunctive brexpiprazole on depressive symptoms among patients with MDD and anxiety symptoms.Materials and methodsThis was a post hoc analysis of 1,171 patients from the 6-week, randomized, double-blind phases of three studies in adults with MDD and inadequate response to ADTs (NCT01360645, NCT01360632, NCT02196506). Data were pooled for brexpiprazole 2-3 mg/day and for placebo (adjunct to ADT). Montgomery-Åsberg Depression Rating Scale Total score changes were assessed in subgroups of patients with and without anxious distress (based on proxies for the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition criteria) and anxious depression (defined as a Hamilton Depression Rating Scale Anxiety/somatization factor score of ?7). Safety was assessed by the incidence of treatment-emergent adverse events (TEAEs).ResultsBenefits were seen for adjunctive brexpiprazole (compared with adjunctive placebo) in both anxiety definition subgroups. For patients with anxious distress, the least squares mean difference (95% CI) at week 6 was -3.00 (-4.29, -1.71; P<0.0001) and, for those without anxious distress, was -1.38 (-2.71, -0.05; P=0.043). For patients with anxious depression, the difference was -2.19 (-3.60, -0.78; P=0.0023), compared with -2.34 (-3.58, -1.10; P=0.0002) for those without anxious depression. The most common TEAEs among patients with anxiety symptoms receiving ADT + brexpiprazole were akathisia, headache, restlessness, somnolence, and weight increase. There were no clinically meaningful differences in the rates of these TEAEs according to the presence or absence of anxiety symptoms.ConclusionAdjunctive brexpiprazole 2-3 mg/day may be efficacious in reducing depressive symptoms, and was well tolerated, in patients with clinically relevant anxiety symptoms.

Dataset Information

Switching from Inadequate Adjunctive or Combination Treatment Options to Brexpiprazole Adjunctive to Antidepressant: An Open-Label Study on the Effects on Depressive Symptoms and Cognitive and Physical Functioning.

Background

Methods

Results

Conclusions

Publications

Switching from Inadequate Adjunctive or Combination Treatment Options to Brexpiprazole Adjunctive to Antidepressant: An Open-Label Study on the Effects on Depressive Symptoms and Cognitive and Physical Functioning.

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