brexpiprazole and Anxiety-Disorders

Anxiety symptoms are prevalent in major depressive disorder (MDD) and are associated with greater illness severity, suicidality, impaired functioning and poor response to antidepressant treatment (ADT). The efficacy and safety of brexpiprazole - a serotonin-dopamine activity modulator - as adjunctive treatment in patients with MDD was recently evaluated in two phase 3 studies. We here present a post-hoc analysis of the efficacy of adjunctive brexpiprazole in patients with MDD and symptoms of anxious distress, defined using proxies for DSM-5 criteria.. Eligible patients were randomized to 2mg brexpiprazole+ADT or placebo+ADT (NCT01360645); or 1mg brexpiprazole+ADT, 3mg brexpiprazole+ADT, or placebo+ADT (NCT01360632), respectively. Patients were defined as having anxious distress if they had ≥2 of the symptoms tension (MADRS item 3 score ≥3), restlessness (IDS item 24 score ≥2), concentration (MADRS item 6 score ≥3), or apprehension (HAM-D item 10 score ≥3). Primary efficacy endpoint was change in MADRS total score from baseline to Week 6.. 55% of the patients had anxious distress at baseline. Adjunctive brexpiprazole showed greater improvement than adjunctive placebo on the primary efficacy endpoint in both patients with (least square mean difference to placebo+ADT: 2mg+ADT: -2.95, p=0.0023; 3mg+ADT: -2.81, p=0.0027); and without anxious distress (1mg+ADT: -2.37, p=0.0093; 3mg+ADT: -2.23, p=0.0131). Brexpiprazole in patients with anxious distress was not associated with an increased incidence of activating adverse events (e.g., akathisia).. Adjunctive brexpiprazole 2-3mg may be efficacious in reducing depressive symptoms and is well tolerated, in patients with MDD and anxious distress.

Topics: Adult; Antidepressive Agents; Anxiety Disorders; Depression; Depressive Disorder, Major; Dopamine Agonists; Double-Blind Method; Drug Therapy, Combination; Female; Humans; Male; Middle Aged; Psychomotor Agitation; Quinolones; Serotonin Agents; Thiophenes; Treatment Outcome

Although the sedative and extrapyramidal side effects associated with first-generation antipsychotics are well known, some second-generation antipsychotics are also associated with substantial sedation and activation effects. In this Academic Highlights article, 4 experts on depression from the fields of psychiatry and primary care take a closer look at activation and sedation effects of atypical antipsychotics in patients with MDD. They examine the likelihood of each agent to cause these effects; the impact of these effects on patient functioning, quality of life, and treatment adherence; and the question of whether leveraging activation and sedation to address acute symptoms is ever advisable.

Topics: Adult; Antidepressive Agents; Antipsychotic Agents; Anxiety Disorders; Aripiprazole; Arousal; Comorbidity; Delayed-Action Preparations; Depressive Disorder, Major; Drug Approval; Drug Therapy, Combination; Female; Humans; Hypnotics and Sedatives; Male; Middle Aged; Practice Patterns, Physicians'; Quality of Life; Quetiapine Fumarate; Quinolones; Sleep Initiation and Maintenance Disorders; Thiophenes