Adjunctive brexpiprazole for elderly patients with major depressive disorder: An open‐label, long‐term safety and tolerability study

Abstract

ObjectivesThe objective of this study was to evaluate the long‐term safety and tolerability of flexible‐dose brexpiprazole adjunct to antidepressant treatment (ADT) in elderly patients with major depressive disorder (MDD).MethodsElderly patients (≥65 years) with MDD and inadequate response to ≥1 ADT during the current episode were recruited to a 26‐week, interventional, open‐label study (NCT02400346) at outpatient centers in the USA and Europe. All patients received brexpiprazole 1 to 3 mg/day adjunct to their current ADT. Safety outcomes included adverse events (AEs), movement disorder scales, and standard safety assessments (vital signs, laboratory safety parameters, physical examination, electrocardiograms). Exploratory efficacy outcomes included the Montgomery–Åsberg Depression Rating Scale (MADRS), Clinical Global Impressions‐Severity of Illness (CGI‐S), and Social Adaptation Self‐Evaluation Scale (SASS).ResultsOf the 132 treated patients, 88 (66.7%) completed the study and 44 (33.3%) withdrew, including 24 who withdrew because of AEs (18.2%). Overall, 102 patients (77.3%) experienced ≥1 treatment‐emergent AE (TEAE), which were mostly mild or moderate in severity. Treatment‐emergent AEs with the highest incidence were fatigue (15.2%) and restlessness (12.9%). The most common TEAE leading to withdrawal was fatigue (3.0%). No consistent clinically relevant findings were seen with regard to movement disorder scales or standard safety assessments. Mean (standard error) efficacy score changes from baseline to week 26 were: MADRS total, −14.5 (0.9); CGI‐S, −1.8 (0.1); and SASS, 3.2 (0.5).ConclusionsLong‐term (26‐week) treatment with adjunctive brexpiprazole was generally well tolerated in elderly patients with MDD and inadequate response to prior ADT. Improvements were observed in depressive symptoms and social functioning.

Efficacy and safety of brexpiprazole in acute management of psychiatric disorders: a meta-analysis of randomized controlled trials

“…Efficacy of Brexpiprazole as adjunct therapy in the management of Major Depressive Disorder 7 RCTs for brexpiprazole role in MDD were included, where brexpiprazole was compared with placebo (including one trial (Hobart et al, 2018) In a total of 3401 patients treated with brexpiprazole compared to 3514 patients who received placebo, the overall risk ratio for trial discontinuation due to adverse effects is 0.90 [0.74 to 1.10], p=0.30 (Figure 4A). There is variation among the studies with some favoring brexpiprazole, while others favoring placebo; with a moderate to high heterogeneity (I 2 = 53%).…”

“…The scant evidence regarding long term usage of brexpiprazole highlighted its association with mild or moderate in severity side effects such as weight increase (17.7%) -mean increase in body weight was 2.7 kg, somnolence (8.0%), headache (7.2%), akathisia (6.7%), increased appetite (6.3%), insomnia (6.3%), fatigue (6.1%) and anxiety (5.2%) (Hobart, Zhang, Skuban et al, 2019). In elderly, adjunctive brexpiprazole was generally well tolerated with improvements in depressive symptoms and social functioning (Lepola et al, 2018). Therefore, it is recommended that further research using different doses with long-treatment is conducted for a more comprehensive understanding of brexpiprazole role in the management of psychiatric conditions.…”

Brexpiprazole for the maintenance treatment of adults with schizophrenia: an evidence-based review and place in therapy

“…At this time, there are very few safety data in patients with schizophrenia >65 years old, although this population has been studied in a 26-week open-label safety trial for adjunctive brexpiprazole use in the treatment of depression;29 in this analysis, no new concerns were identified, but the average dose was 1.8 mg, so it may not be appropriate to extrapolate these results to elderly patients with schizophrenia.…”

Efficacy and safety of brexpiprazole as adjunctive treatment in major depressive disorder: overview of four short-term studies

“…Furthermore, an exploratory open-label study found that physiologic measures of sleep and daytime alertness were improved in patients with sleep disturbances treated with adjunctive brexpiprazole [31]. Elderly patients (≥65 years) with MDD have shown improvements in depressive symptoms, social functioning, and quality of life during open-label treatment with adjunctive brexpiprazole [32]. The benefits of brexpiprazole in anxious, irritated, and sleep-disturbed patients is consistent with its partial agonism at 5-HT 1A and D 2 /D 3 receptors, and its antagonism at 5-HT 2A and α 1 receptors [8,30,31].…”