Adjunctive Therapy of Major Depressive Disorder
Brexpiprazole is used orally as an adjunct to antidepressants for the treatment of major depressive disorder.
The adjunctive antidepressant efficacy of brexpiprazole was established in 2 short-term, double-blind, placebo-controlled, fixed-dose studies of 6 weeks' duration (studies 1 and 2) in adults who met DSM-IV-TR criteria for major depressive disorder with or without symptoms of anxiety and who had an inadequate response to previous antidepressant therapy (1-3 courses) in the current episode and had also demonstrated an inadequate response during an 8-week prospective treatment period of antidepressant therapy with delayed-release duloxetine, escitalopram, fluoxetine, extended-release paroxetine, sertraline, or extended-release venlafaxine. The primary efficacy end point in these studies was change from baseline to week 6 on the Montgomery-Asberg Depression Rating Scale (MADRS) total score. In study 1, patients were randomized to receive either brexpiprazole 2 mg once daily or placebo in addition to their antidepressant therapy; in study 2, patients were randomized to receive brexpiprazole 1 or 3 mg once daily or placebo as adjunctive therapy. Brexpiprazole therapy was initiated at a dosage of 0.5 mg once daily in all patients, then the dosage was increased to 1 mg once daily at week 2 in all treatments groups; the dosage was then either maintained at 1 mg once daily or increased to 2 or 3 mg once daily, based on treatment assignment, from week 3 onward. In studies 1 and 2, brexpiprazole at a dosage of 2 or 3 mg daily was superior to placebo in reducing mean MADRS total scores at week 6 and was generally well tolerated. An analysis of population subgroups did not reveal evidence of differential response to adjunctive brexpiprazole therapy based on age, gender, race, or choice of prospective antidepressant.
The manufacturer states that the need for continued therapy and appropriate dosage of brexpiprazole should be reassessed periodically in patients with major depressive disorder.
(See Dosage and Administration: Dosage.)
Drug therapy is integral to the management of acute psychotic episodes in patients with schizophrenia and generally is required for long-term stabilization to sustain symptom remission or control and to minimize the risk of relapse. Antipsychotic agents are the principal class of drugs used for the management of all phases of schizophrenia. Patient response and tolerance to antipsychotic agents are variable, and patients who do not respond to or tolerate one drug may be successfully treated with an agent from a different class or with a different adverse effect profile.
Brexpiprazole is an atypical antipsychotic that is administered orally in the treatment of schizophrenia. Schizophrenia is a major psychotic disorder that frequently has devastating effects on various aspects of the patient's life and carries a high risk of suicide and other life-threatening behaviors. Manifestations of schizophrenia involve multiple psychologic processes, including perception (e.g., hallucinations), ideation, reality testing (e.g., delusions), emotion (e.g., flatness, inappropriate affect), thought processes (e.g., loose associations), behavior (e.g., catatonia, disorganization), attention, concentration, motivation (e.g., avolition, impaired intention and planning), and judgment. The principal manifestations of this disorder usually are described in terms of positive and negative (deficit) symptoms and, more recently, disorganized symptoms. Positive symptoms include hallucinations, delusions, bizarre behavior, hostility, uncooperativeness, and paranoid ideation, while negative symptoms include restricted range and intensity of emotional expression (affective flattening), reduced thought and speech productivity (alogia), anhedonia, apathy, and decreased initiation of goal-directed behavior (avolition). Disorganized symptoms include disorganized speech (thought disorder) and behavior and poor attention.
Short-term efficacy of oral brexpiprazole monotherapy in the acute treatment of schizophrenia has been established in 2 randomized, multicenter, double-blind, placebo-controlled, fixed-dose studies of 6 weeks' duration (studies 3 and 4) in adults who met DSM-IV-TR criteria for schizophrenia and were experiencing an acute exacerbation of psychotic symptoms. Both studies evaluated fixed brexpiprazole dosages of 2 or 4 mg once daily. Brexpiprazole therapy was initiated at a dosage of 1 mg once daily, given on days 1 through 4, then the dosage was increased to 2 mg once daily on days 5 to 7; the dosage was then either maintained at 2 mg once daily or increased to 4 mg once daily, based on treatment assignment, for 5 weeks. The primary efficacy end point in these studies was the change from baseline to week 6 on the Positive and Negative Syndrome Scale (PANSS) total score. In both studies, brexpiprazole 4 mg once daily was found to be more effective than placebo in improving the PANSS total score at week 6; the 2-mg daily dosage of brexpiprazole was more effective than placebo only in study 3. An examination of population subgroups did not reveal any clear evidence of differential responsiveness to the drug based on age, gender, or race.
Efficacy and safety of brexpiprazole in the maintenance treatment of schizophrenia have been established in a randomized, multicenter withdrawal study (study 5). Adults with schizophrenia were stabilized for at least 12 weeks on 1-4 mg daily of brexpiprazole and were then randomized in the double-blind treatment phase to either continue brexpiprazole at their achieved stable dosage or to switch to placebo for up to 52 weeks. The primary efficacy end point in this study was time from randomization to impending relapse during the double-blind phase. A prespecified interim analysis demonstrated a substantially longer time to relapse in patients randomized to brexpiprazole therapy compared with the placebo recipients. The study was therefore terminated early because maintenance of efficacy had been demonstrated. Long-term brexpiprazole therapy also was found to be well tolerated in this study.
The American Psychiatric Association (APA) considers most atypical antipsychotic agents first-line drugs for the management of the acute phase of schizophrenia (including first psychotic episodes), principally because of the decreased risk of adverse extrapyramidal effects and tardive dyskinesia, with the understanding that the relative advantages, disadvantages, and cost-effectiveness of conventional and atypical antipsychotic agents remain controversial. The APA states that, with the possible exception of clozapine for the management of treatment-resistant symptoms, there currently is no definitive evidence that one atypical antipsychotic agent will have superior efficacy compared with another agent in the class, although meaningful differences in response may be observed in individual patients. Conventional antipsychotic agents also may be an appropriate first-line option for some patients, including those who have been treated successfully in the past with or who prefer conventional agents. The choice of an antipsychotic agent should be individualized, considering past response to therapy, current symptomatology, concurrent medical conditions, other medications and treatments, adverse effect profile, and the patient's preference for a specific drug, including route of administration.
For additional information on the symptomatic management of schizophrenia, including treatment recommendations, .