Patient-reported efficacy of adjunctive brexpiprazole in major depressive disorder in a phase 4, open-label, interventional study

Abstract

Objectives: In ENGAGE, patients with major depressive disorder (MDD) demonstrated improvements in patient-reported depression and life engagement while taking adjunctive brexpiprazole. This analysis aimed to further characterize patient perspectives on the effects of adjunctive brexpiprazole, using patient diary data from ENGAGE, and describe the development of a 'word of the day' activity. Methods: Prior to ENGAGE, word lists describing a 'good,' 'average,' and 'bad' day with depression were generated from semi-structured interviews with patients with MDD. ENGAGE (ClinicalTrials.gov identifier: NCT04830215) was an 8-week, phase 4, single-arm, open-label study of adjunctive brexpiprazole 0.5-2 mg/day in patients with MDD and inadequate response to antidepressant treatment. Patient diaries were completed periodically at home, comprising the Patient Global Impression-Severity of illness (PGI-S), Patient Global Impression-Improvement (PGI-I), and a 'word of the day' activity in which patients selected one word to describe how they felt that day. This analysis evaluated mean change in PGI-S scores (mixed model for repeated measures), mean PGI-I scores (descriptive statistics), PGI-S response and PGI-S sustained response (Kaplan-Meier), PGI-I response (normal approximation), and 'word of the day' (descriptive statistics). Results: In the interviews, 20 patients used 132 words to describe living with depression. Five words of each valence (positive, neutral, negative) were selected for ENGAGE. 122 patients were enrolled in ENGAGE; 120 had evaluable diary data. PGI-S score improved from baseline to week 8 (least squares mean change [standard error]: -1.5 [0.2]; nominal p<0.001; effect size: 1.04). PGI-I scores at week 8 indicated 'minimal improvement' to 'much improvement' (mean [standard deviation]: 2.6 [1.1]). At week 8, rates of PGI-S response, sustained PGI-S response, and PGI-I response were 86.0% (95% confidence interval: 77.1, 92.8), 67.9% (54.5, 80.6), and 47.1% (38.1, 56.0), respectively. On 'word of the day,' the proportion of positive and neutral words increased from baseline to week 8, and the proportion of negative words decreased. Conclusions: Patient-reported diary data revealed early and sustained improvements in depressive symptom severity during 8 weeks of adjunctive brexpiprazole treatment. 'Word of the day' may be an effective qualitative tool for future trials. PLAIN LANGUAGE SUMMARY Major depressive disorder is a common mental illness that involves low mood and a lack of interest or enjoyment in activities. For people who need medicine to treat their depression, 'antidepressant' treatment is part of the standard of care. However, some people continue to show depression symptoms despite taking an antidepressant. For these people, it is common practice to add an 'antipsychotic' medicine such as brexpiprazole on top of their antidepressant to further improve symptoms. Brexpiprazole added to an antidepressant can be effective in treating depression, though it is also important to capture patients' views on this. A recent study in people with depression used several patient-based measures to assess their views about brexpiprazole treatment (added to an antidepressant). In this study, patients said that their depression improved and that they felt more engaged with life after treatment with brexpiprazole (described in a previous paper). As part of this study, patients were also asked to fill out a diary of their personal impressions of their symptoms while taking brexpiprazole.The diary contained several questionnaires, including a list of words to describe how patients felt each day. Results showed that, after 8 weeks of treatment with brexpiprazole added to their antidepressant, patients' depression symptoms improved-from their own point of view.