brexpiprazole and Psychomotor-Agitation

Limited efficacy on negative and cognitive symptoms and adverse effects of current antipsychotics raise the need of developing new antipsychotics. Brexpiprazole, a new antipsychotic drug approved by the U.S. Food and Drug Administration in July 2015 for the treatment of schizophrenia, is a novel serotonin-dopamine receptor modulator with partial agonist activity at serotonin 1A (5-HT

Topics: Antipsychotic Agents; Cognition; Dopamine; Humans; Psychomotor Agitation; Quinolones; Receptors, Dopamine D2; Schizophrenia; Serotonin; Thiophenes

To assess the efficacy, safety, and tolerability of brexpiprazole as adjunctive treatment in adults with major depressive disorder (MDD) and an inadequate response to prior antidepressant treatment (ADT).. Patients with a current major depressive episode after prior treatment with 1-3 ADTs entered an 8- or 10-week prospective treatment phase in which they received double-blind placebo adjunct to open-label ADT. Inadequate responders were randomized (2:2:1) to brexpiprazole 2-3 mg/day, placebo, or quetiapine extended-release (XR) 150-300 mg/day, adjunct to the same ADT, for 6 weeks. The primary efficacy endpoint was the change from baseline (randomization) to week 6 in Montgomery-Åsberg Depression Rating Scale (MADRS) total score. The key secondary efficacy endpoint was the change in Sheehan Disability Scale (SDS) mean score.. Adjunctive brexpiprazole showed a greater improvement in MADRS total score than adjunctive placebo (least squares mean difference [95% confidence interval] = -1.48 [-2.56, -0.39]; p = .0078), whereas adjunctive quetiapine XR did not separate from placebo (-0.30 [-1.63, 1.04]; p = .66). Adjunctive brexpiprazole failed to separate from placebo on the SDS mean score (-0.23 [-0.52, 0.07]; p = .13), but did improve functioning on two of the three SDS items (family life and social life). The most frequent treatment-emergent adverse events in patients receiving brexpiprazole were akathisia (6.1%), somnolence (5.6%), and headache (5.6%).. Adjunctive brexpiprazole 2-3 mg/day improved symptoms of depression compared with adjunctive placebo in patients with MDD and an inadequate response to ADTs, and was well tolerated with no unexpected side effects.

Topics: Adult; Antidepressive Agents; Depressive Disorder, Major; Double-Blind Method; Drug Therapy, Combination; Female; Headache; Humans; Male; Middle Aged; Prospective Studies; Psychomotor Agitation; Quetiapine Fumarate; Quinolones; Thiophenes; Treatment Outcome

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

Topics: Alzheimer Disease; Antipsychotic Agents; Humans; Psychomotor Agitation; Quinolones; Thiophenes

Brexpiprazole (also known as OPC-34712 or Lu-AF41156) is a novel molecular compound chemically and structurally similar to aripiprazole. This drug is currently under review by the U.S. Food and Drug Administration as a monotherapy for schizophrenia and an adjunct to antidepressant medication for major depressive disorder. Additional clinical trials include studies of brexpiprazole in attention-deficit/hyperactivity disorder and posttraumatic stress disorder, and for agitation associated with dementia of the Alzheimer's type. Brexpiprazole is an example that illustrates how pharmacological drug diversity may be translated to multipurpose uses.

Topics: Antipsychotic Agents; Attention Deficit Disorder with Hyperactivity; Depressive Disorder, Major; Humans; Psychomotor Agitation; Quinolones; Schizophrenia; Stress Disorders, Post-Traumatic; Thiophenes