Safety and Tolerability of Brexpiprazole in Participants with Agitation Associated with Dementia due to Alzheimer's Disease: Pooled Analysis of Three Randomized Trials and an Extension Trial.

Background And Objective: Older adults with dementia are particularly vulnerable to antipsychotic side effects. Brexpiprazole, an atypical antipsychotic, is approved in a number of countries for the treatment of agitation associated with dementia due to Alzheimer's disease. This pooled analysis aimed to evaluate the safety and tolerability of brexpiprazole in this patient population.

Safety and Tolerability of Brexpiprazole in Adolescents With Schizophrenia: A Long-Term, Open-Label Study.

Objective: This study aimed to characterize long-term safety and tolerability of brexpiprazole, an atypical antipsychotic, as maintenance treatment in adolescents with schizophrenia.

Method: This was an interim analysis of an ongoing, 24-month, multicenter, single-arm, open-label, outpatient study of oral brexpiprazole 1 to 4 mg/day (flexible dose) in adolescents aged 13 to 17 years with schizophrenia. Primary end points were incidence of treatment-emergent adverse events (TEAEs), TEAEs by severity, serious TEAEs, and adverse events leading to study discontinuation.

Efficacy and safety of brexpiprazole in adolescents with schizophrenia: a multicountry, randomised, double-blind, placebo-controlled, phase 3 trial with an active reference.

Background: New treatment options are needed for adolescent schizophrenia, partly due to an unfavourable risk-benefit profile of current options. This trial aimed to evaluate the short-term efficacy and safety of brexpiprazole in adolescents with schizophrenia.

Methods: This multicountry, randomised, double-blind, parallel-arm, placebo-controlled, phase 3 trial with an active reference was done at 62 outpatient sites in ten countries.

Brexpiprazole in Combination With Sertraline and as Monotherapy in Posttraumatic Stress Disorder: A Full-Factorial Randomized Clinical Trial.

To investigate the efficacy, safety, and tolerability of brexpiprazole in combination with sertraline and as monotherapy for posttraumatic stress disorder (PTSD). The trial comprised a 1-week placebo run-in period followed by an 11-week, randomized, double-blind, active-referenced, placebo-controlled, parallel-arm treatment period (with 14-day follow-up). The trial ran from January 2017-November 2018 at 48 clinical trial sites in the United States.

Safety and Efficacy of Brexpiprazole in the Treatment of Irritability Associated with Autism Spectrum Disorder: An 8-Week, Phase 3, Randomized, Double-Blind, Placebo-Controlled Trial and 26-Week Open-Label Extension in Children and Adolescents.

The effective management of irritability is a key need in young people with autism spectrum disorder (ASD). We evaluated the efficacy and safety of brexpiprazole in children and adolescents with irritability associated with ASD. This was an 8-week, phase 3, randomized, double-blind, placebo-controlled trial (NCT04174365) and 26-week, open-label extension (OLE, NCT04258839) of brexpiprazole (0.

Brexpiprazole and Sertraline Combination Treatment in Posttraumatic Stress Disorder: A Phase 3 Randomized Clinical Trial.

Importance: New pharmacotherapy options are needed for posttraumatic stress disorder (PTSD).

Objective: To investigate the efficacy, safety, and tolerability of brexpiprazole and sertraline combination treatment (brexpiprazole + sertraline) compared with sertraline + placebo for PTSD.

Design, Setting, And Participants: This was a parallel-design, double-blind, randomized clinical trial conducted from October 2019 to August 2023.

Brexpiprazole for the treatment of agitation associated with dementia due to Alzheimer's disease: A 12-week, active-treatment, extension trial.

Background: A 12-week randomized controlled trial demonstrated that brexpiprazole is efficacious for treating agitation in patients with dementia due to Alzheimer's disease.

Objective: To assess the long-term safety and tolerability of brexpiprazole for the treatment of agitation associated with dementia due to Alzheimer's disease.

Methods: This 12-week, active-treatment (oral brexpiprazole 2 or 3 mg/day) extension trial ran from October 2018-September 2022 at 66 sites in Europe/US.

Defining a clinically meaningful within-patient change threshold for the Cohen-Mansfield Agitation Inventory in Alzheimer's dementia.

Introduction: The Cohen-Mansfield Agitation Inventory (CMAI) quantifies the frequency of agitation behaviors in elderly persons. This analysis of data from the brexpiprazole clinical program aimed to determine a meaningful within-patient change (MWPC) threshold for CMAI Total score among patients with agitation associated with dementia due to Alzheimer's disease.

Methods: Data were included from three 12-week, multicenter, randomized, double-blind, placebo-controlled, parallel-arm trials of brexpiprazole for the treatment of agitation associated with dementia due to Alzheimer's disease (ClinicalTrials.

Brexpiprazole for the Treatment of Agitation in Alzheimer Dementia: A Randomized Clinical Trial.

Importance: Agitation is a prevalent, distressing, and burdensome manifestation of Alzheimer dementia in need of an efficacious, safe, and well-tolerated treatment.

Objective: To confirm the efficacy, safety, and tolerability of brexpiprazole in patients with agitation in Alzheimer dementia.

Design, Setting, And Participants: This randomized clinical trial was a 12-week, double-blind, placebo-controlled, fixed-dose, parallel-arm trial that ran from May 2018 to June 2022 at 123 clinical trial sites in Europe and the United States.

Consistency checks to improve measurement with the Young Mania Rating Scale (YMRS).

Background: Mitigating rating inconsistency can improve measurement fidelity and detection of treatment response.

Methods: The International Society for CNS Clinical Trials and Methodology convened an expert Working Group that developed logical consistency (LC) checks for ratings of the Young Mania Rating Scale (YMRS), which is widely used in studies of mood and bipolar disorders. LC and statistical outlier-response pattern checks (SC) were applied to 63,228 YMRS administrations from 14 clinical trials evaluating treatments for bipolar disorder.

Defining Clinical Trial Estimands: A Practical Guide for Study Teams with Examples Based on a Psychiatric Disorder.

While the ICH E9(R1) Addendum on "Estimands and Sensitivity Analysis in Clinical Trials" was released in late 2019, the widespread implementation of defining and reporting estimands across clinical trials is still in progress and the engagement of non-statistical functions in this process is also in progress. Case studies are sought after, especially those with documented clinical and regulatory feedback. This paper describes an interdisciplinary process for implementing the estimand framework, devised by the Estimands and Missing Data Working Group (a group with clinical, statistical, and regulatory representation) of the International Society for CNS Clinical Trials and Methodology.

Consistency checks to improve measurement with the Hamilton Rating Scale for Anxiety (HAM-A).

Background: Mitigating rating inconsistency can improve measurement fidelity and detection of treatment response.

Methods: The International Society for CNS Clinical Trials and Methodology convened an expert Working Group that developed consistency checks for ratings of the Hamilton Anxiety Rating Scale (HAM-A) and Clinical Global Impression of Severity of anxiety (CGIS) that are widely used in studies of mood and anxiety disorders. Flags were applied to 40,349 HAM-A administrations from 15 clinical trials and to Monte Carlo-simulated data as a proxy for applying flags under conditions of inconsistency.

Effects of Brexpiprazole on Functioning in Patients With Schizophrenia: Post Hoc Analysis of Short- and Long-Term Studies.

To evaluate the short- and long-term effects of brexpiprazole on patient functioning in schizophrenia. Data were included from three 6-week, randomized, double-blind, placebo-controlled studies (hospitalized patients); a 52-week, randomized, double-blind, placebo-controlled maintenance treatment study (terminated early by the study sponsor based on the positive result of an interim analysis); and two 52-week, open-label extension studies-all in patients with schizophrenia ( criteria) and conducted from July 2011-February 2016. Patients allocated to oral brexpiprazole received 2-4 mg/d (short-term studies) or 1-4 mg/d (long-term studies).

Consistency checks to improve measurement with the Hamilton Rating Scale for Depression (HAM-D).

Background: Symptom manifestations in mood disorders can be subtle. Cumulatively, small imprecisions in measurement can limit our ability to measure treatment response accurately. Logical and statistical consistency checks between item responses (i.

Effects of Brexpiprazole Across Symptom Domains in Patients With Schizophrenia: Analysis of Short- and Long-Term Studies.

The successful treatment of schizophrenia entails improvement across a spectrum of symptoms. The aim of this analysis was to characterize the short- and long-term effects of brexpiprazole on Positive and Negative Syndrome Scale (PANSS) 'Marder factors.' Data were included from three 6-week, randomized, double-blind, placebo-controlled studies; a 52-week, randomized, double-blind, placebo-controlled maintenance treatment study; and two 52-week open-label extension (OLEx) studies-all in schizophrenia (DSM-IV-TR criteria).

Two randomized, double-blind, placebo-controlled trials and one open-label, long-term trial of brexpiprazole for the acute treatment of bipolar mania.

Background: Brexpiprazole is a dopamine/serotonin receptor partial agonist (D, 5-HT) and antagonist (5-HT) approved for treatment of schizophrenia and major depressive disorder (adjunct to antidepressants).

Aims: This study aimed to investigate brexpiprazole as monotherapy in acute mania (bipolar I disorder) in two short-term (ST) studies (study 080 and study 081) and one open-label (OL) extension (study 083).

Methods: ST studies were three-week randomized, double-blind, flexible dose (2-4 mg/day), placebo-controlled studies.

A Long-Term, Open-Label Study to Evaluate the Safety and Tolerability of Brexpiprazole as Adjunctive Therapy in Adults With Major Depressive Disorder.

Background: Long-term treatment is recommended in major depressive disorder (MDD) to prevent relapse and to restore functioning. The aim of this study (Orion; NCT01360866) was to assess the long-term safety, tolerability, and efficacy of open-label treatment with adjunctive brexpiprazole in adult patients with MDD.

Methods: Patients rolled over into this 52-week study (amended to 26 weeks) from 3 randomized, double-blind, placebo-controlled studies.

A randomised, placebo-controlled 24-week study evaluating adjunctive brexpiprazole in patients with major depressive disorder.

Objective: To evaluate brexpiprazole adjunctive to antidepressant therapies (ADTs) as maintenance treatment in patients with major depressive disorder with inadequate response to ADT, utilising a novel study design.

Methods: The study comprised an 8-week prospective treatment period with open-label ADT with double-blind placebo treatment and a 24-week randomised treatment period. Investigators and patients were blinded to treatment periods, randomisation criteria, and timing of randomisation.

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

Objectives: The 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).

Methods: Elderly 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.

A Randomized, Placebo-Controlled Study of the Efficacy and Safety of Fixed-Dose Brexpiprazole 2 mg/d as Adjunctive Treatment of Adults With Major Depressive Disorder.

Objective: To assess the efficacy, safety, and tolerability of brexpiprazole as adjunct to antidepressant treatment (ADT) in adults with major depressive disorder (MDD) and inadequate response to ADTs.

Methods: Outpatients with inadequate response to 1-3 ADTs during their current depressive episode (DSM-IV-TR criteria) were administered prospective, open-label ADT. Those patients with inadequate response to prospective ADT were randomized to double-blind, adjunctive brexpiprazole 2 mg/d or placebo.

Efficacy and safety of flexibly dosed brexpiprazole for the adjunctive treatment of major depressive disorder: a randomized, active-referenced, placebo-controlled study.

Objective: 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).

Methods: 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.