Brexpiprazole for Bipolar Disorder
Recruiting in Palo Alto (17 mi)
Age: 18+
Sex: Any
Travel: May be covered
Time Reimbursement: Varies
Trial Phase: Phase 3
Recruiting
Sponsor: Douglas Mental Health University Institute
Stay on your current meds
No Placebo Group
Pivotal Trial (Near Approval)
Prior Safety Data
Approved in 6 jurisdictions
Trial Summary
What is the purpose of this trial?Bipolar disorder (BD) is a frequent and lifelong recurrent mood disorder with treatment-resistant depressive episodes. Importantly, depressive symptoms and cognitive decline are major determinants of functionality and quality of life in this clinical population. There is robust evidence that individuals with BD have neurocognitive deficits (especially in memory and executive functioning domains) compared to the healthy population. These deficits are present in all mood states and can greatly affect patients' functional capacity, often more so than mood symptoms themselves. Many pharmacological treatments for BD adversely affect cognition, and those that are beneficial can be difficult to use. There is thus a pressing need to identify a safe, easy-to-use medication that can target both cognitive deficits and depressive symptoms in BD. It is expected that Brexpiprazole adjunctive treatment will be efficacious in treating BD type I and type II depression by improving mood symptoms, as well as cognitive capacity and global functioning, and that such changes will be accompanied by concurrent alterations in associated brain structures.
Do I have to stop taking my current medications for the trial?
The trial requires that you stop taking certain medications. You cannot participate if you are treated with fluoxetine, carbamazepine, risperidone, olanzapine, quetiapine (over 100mg/day), ziprazidone, or any other antipsychotic. However, you must be on a mood stabilizer like lithium, valproate, lamotrigine, or quetiapine (up to 100mg/day).
What data supports the idea that the drug Brexpiprazole for Bipolar Disorder is an effective treatment?
The available research shows that Brexpiprazole is effective for treating schizophrenia and as an additional treatment for major depressive disorder. It has been shown to improve symptoms and is generally well tolerated. However, there is no specific data provided about its effectiveness for treating Bipolar Disorder.
12345What safety data is available for Brexpiprazole?
Brexpiprazole, also known as Rexulti, is generally well tolerated with a relatively low incidence of activating and sedating adverse effects. It has been associated with moderate weight gain and small changes in metabolic parameters, which are not clinically significant. The most common adverse event is increased weight, with about 10% of patients gaining ≥7% body weight in short-term studies. Akathisia rates are low, and there are minimal effects on prolactin and the ECG QTc interval. Brexpiprazole is approved for schizophrenia and as an adjunct for major depressive disorder, with ongoing trials for other conditions.
12346Is the drug Brexpiprazole a promising treatment for Bipolar Disorder?
Brexpiprazole is a promising drug because it has been effective in treating major depressive disorder and schizophrenia, showing improvements in symptoms and being well tolerated by patients. It offers a new option for those who haven't fully responded to other treatments.
12345Eligibility Criteria
Adults aged 18-75 with Bipolar I Disorder currently experiencing treatment-resistant depression, who have tried at least one other treatment without success. Participants must be on a mood stabilizer and have normal heart function. They cannot join if they are at high suicide risk, have psychotic symptoms, certain neurocognitive disorders, uncontrolled seizures, known allergies to Brexpiprazole or its components including lactose intolerance.Participant Groups
The trial is testing the effectiveness of Brexpiprazole as an additional treatment for depressive episodes in Bipolar I Disorder. It aims to improve mood symptoms and cognitive functions while monitoring changes in brain structures associated with these improvements.
1Treatment groups
Experimental Treatment
Group I: PatientExperimental Treatment1 Intervention
Individuals diagnosed with Bipolar Disorder Type I or Type II and suffering a major depressive episode who will receive an adjunctive and variable dose of Brexpiprazole treatment
Find A Clinic Near You
Research locations nearbySelect from list below to view details:
Douglas Mental Health University InstituteMontreal, Canada
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Who is running the clinical trial?
Douglas Mental Health University InstituteLead Sponsor
McMaster UniversityCollaborator
Jewish General HospitalCollaborator
References
Brexpiprazole (Rexulti): A New Monotherapy for Schizophrenia and Adjunctive Therapy for Major Depressive Disorder. [2022]Brexpiprazole (Rexulti): a new monotherapy for schizophrenia and adjunctive therapy for major depressive disorder.
Brexpiprazole: First Global Approval. [2018]Brexpiprazole (Rexulti®) is an atypical antipsychotic that has been developed by Otsuka Pharmaceutical Co. Ltd and H. Lundbeck A/S as an oral treatment for several psychiatric disorders. Brexpiprazole is a novel serotonin-dopamine activity modulator that acts as a partial agonist of serotonin 1A (5-HT1A) and dopamine D2 receptors, as well as a potent antagonist of 5-HT2A receptors and noradrenergic α1B and α2C receptors. In July 2015, brexpiprazole received its first approval in the USA for use as an adjunctive treatment of major depressive disorder (MDD) and the treatment of schizophrenia. In several countries, brexpiprazole is in development for MDDs, schizophrenia, post-traumatic stress disorder and agitation in patients with dementia of the Alzheimer's type. This article summarizes the milestones in the development of brexpiprazole leading to its first global approval in MDD and schizophrenia.
Adjunctive Brexpiprazole: A Review in Major Depressive Disorder. [2018]Brexpiprazole (Rexulti(®)) is a serotonin-dopamine activity modulator, with a unique receptor binding profile and low intrinsic D2 activity suggestive of a lower potential than aripiprazole to cause activation-like adverse effects, such as akathisia. The drug was recently approved by the US FDA for adjunctive therapy with antidepressant treatment (ADT) in patients with major depressive disorder (MDD). In two phase III trials, adjunctive oral brexpiprazole 2 or 3 mg once daily was more effective than monotherapy with ADT in improving depressive symptoms in adults with MDD who demonstrated an incomplete response to previous treatment with ADT. Adjunctive brexpiprazole was generally well tolerated in clinical trials, which included treatment periods of up to 52 weeks. Results of ongoing trials should help position the drug in the treatment of MDD. In the meantime, brexpiprazole provides a valid option for patients with persistent symptoms despite standard antidepressant therapy.
Brexpiprazole: A Review in Schizophrenia. [2020]Brexpiprazole (Rxulti®, Rexulti®) is an oral atypical antipsychotic agent approved for the treatment of schizophrenia in the EU (in adult patients) and the USA, as well as in some other countries, including Japan. Like aripiprazole, it is a partial agonist at dopamine D2 and serotonin 5-HT1A receptors and an antagonist at serotonin 5-HT2A receptors. However, brexpiprazole displays less intrinsic activity at D2 receptors and, coupled with actions at 5HT1A, 5HT2A and noradrenaline α1B receptors that are at least as potent as its action at D2 receptors, is predicted to demonstrate a lower propensity for activating adverse events and extrapyramidal symptoms than aripiprazole. Brexpiprazole 2-4 mg/day produced statistically significant and clinically meaningful improvements in overall symptomatology and psychosocial functioning compared with placebo in adults with acute exacerbation of schizophrenia. As maintenance treatment, brexpiprazole 1-4 mg/day significantly delayed the time to relapse compared with placebo in patients who were already stabilized on the drug and was associated with stabilization or continued improvement in patients' symptoms and functioning. Brexpiprazole was generally well tolerated, exhibiting an adverse event profile characterized by a relatively low incidence of activating and sedating adverse effects, small changes in QT interval and metabolic parameters that were not clinically significant, and moderate weight gain. Clinical evidence to date suggests it usefully extends the range of therapeutic options for schizophrenia.
Brexpiprazole: A Review in Schizophrenia. [2018]Oral brexpiprazole (Rexulti(®)) is a partial dopamine D2 agonist, which also has activity at several other receptors. This article reviews the pharmacological properties of brexpiprazole and its clinical efficacy and tolerability in patients with schizophrenia; its use in patients with major depressive disorder is beyond the scope of this review. Brexpiprazole 2-4 mg/day was generally effective in short-term, phase III studies at improving Positive and Negative Symptom Scale scores and other schizophrenia symptoms in patients with acute schizophrenia. Moreover, maintenance treatment with brexpiprazole 1-4 mg/day was associated with a significantly longer time to exacerbation of disease or impending relapse than placebo. The drug was well tolerated in clinical trials, with most serious adverse events in the short term being associated with the underlying disorder. Overall, oral brexpiprazole is a useful treatment option for the treatment of patients with schizophrenia.
Brexpiprazole for the Treatment of Schizophrenia: A Review of this Novel Serotonin-Dopamine Activity Modulator. [2016]Brexpiprazole is an antipsychotic medication and received approval by the U.S. Food and Drug Administration for the treatment of schizophrenia in July 2015. Brexpiprazole acts as a partial agonist at dopamine D2 and serotonin 5-HT1A receptors, and as an antagonist at serotonin 5-HT2A and at adrenergic alpha1B and alpha2C receptors. Compared with aripiprazole, brexpiprazole is more potent at 5-HT1A receptors and displays less intrinsic activity at D2 receptors. The recommended dose range of brexpiprazole for the treatment of schizophrenia is 2-4 mg/day; the recommended titration schedule is to start with 1 mg/day and increase to 2 mg/day on Day 5 to Day 7, then to 4 mg/day on Day 8. Two positive, 6-week, Phase 3 randomized controlled trials in acute schizophrenia demonstrated superiority of brexpiprazole over placebo. Pooled responder rates were 46% for brexpiprazole 2-4 mg/day vs. 31% for placebo, resulting in a number needed to treat (NNT) of 7. In a 52-week, randomized withdrawal study, significantly fewer patients relapsed in the brexpiprazole group compared with placebo (13.5% vs. 38.5%), resulting in an NNT of 4. The most commonly encountered adverse event (incidence ≥4% and at least twice the rate of placebo) is increased weight. Short-term weight gain appears modest (approximately 10% of patients receiving brexpiprazole 1-4 mg/day gained ≥7% body weight from baseline, compared with 4% for those randomized to placebo, resulting in a number needed to harm [NNH] of 17); however, more outliers with an increase of ≥7% of body weight were evident in open-label, 52-week safety studies. Effects on glucose and lipids were small. Rates of akathisia as an adverse event were 5.5% for the pooled doses of brexpiprazole 1-4 mg/day vs. 4.6% for placebo, yielding an NNH of 112. Minimal effects on prolactin were observed, and no clinically relevant effects on the ECG QTc interval were evident. Brexpiprazole is also approved as an adjunct medication for the treatment of major depressive disorder. Phase 3 trials are ongoing in patients with agitation associated with Alzheimer's disease.