Major Depressive Disorder (MDD) is a common mental health condition characterized by persistent sadness, loss of interest or pleasure, and other symptoms that interfere with daily life. Many individuals experience significant challenges when their symptoms do not fully improve with initial antidepressant treatments. For these patients, adjunctive therapy, which involves adding another medication to an existing antidepressant regimen, can be a beneficial strategy to achieve better symptom control. This article explores the use of brexpiprazole in this role, providing insights into its function, how it works, the treatment process, and important safety considerations.
Brexpiprazole’s Role in MDD Treatment
Brexpiprazole, marketed as Rexulti, is an atypical antipsychotic. While initially developed to address conditions like schizophrenia, brexpiprazole has specific approval as an adjunctive therapy for MDD. This means it is not a primary or standalone treatment for depression, but is prescribed in addition to an antidepressant when a patient has not experienced an adequate response to their current medication alone.
Adding brexpiprazole aims to enhance the effectiveness of existing antidepressant treatment. It addresses residual symptoms that persist despite ongoing therapy, helping patients achieve a more complete remission of depressive symptoms. This approach recognizes that some MDD cases may require a broader pharmacological strategy to stabilize mood and improve overall well-being, signifying a targeted effort to improve outcomes for individuals with treatment-resistant depression.
The Neurobiological Mechanism
Brexpiprazole functions as a serotonin-dopamine activity modulator, a term that describes its unique interaction with specific brain receptors. Unlike many standard antidepressants that primarily work by increasing serotonin levels in the brain, brexpiprazole has a more nuanced effect. It acts as a partial agonist at certain serotonin 5-HT1A and dopamine D2 receptors, meaning it partially activates these receptors. Simultaneously, it acts as an antagonist at other receptors, specifically serotonin 5-HT2A receptors, which means it blocks their activity.
This dual action allows brexpiprazole to fine-tune neurotransmitter activity in the brain, rather than simply increasing or decreasing levels of a single chemical. This mechanism is thought to help rebalance brain chemistry in a way that the primary antidepressant alone might not fully accomplish, contributing to improved mood regulation and symptom reduction. Its distinct receptor binding profile, particularly its lower intrinsic activity at the D2 receptor compared to similar medications, is hypothesized to contribute to its specific therapeutic effects and tolerability.
Initiating Treatment and Efficacy
Initiating treatment with adjunctive brexpiprazole typically begins with a low dose, often 0.5 mg or 1 mg taken once daily. A healthcare provider will then gradually increase the dosage, a process known as titration, based on the patient’s clinical response and how well they tolerate the medication. This gradual increase usually occurs in weekly intervals, aiming for a target dose that can range from 1 mg to 2 mg per day, with a maximum recommended dose of 3 mg per day for MDD. The slow titration helps the body adjust to the medication and allows for careful monitoring of any potential side effects.
Patients should understand that it may take several weeks to observe a noticeable improvement in depressive symptoms once brexpiprazole is added to their regimen. Clinical trials have provided evidence of brexpiprazole’s effectiveness in this adjunctive role. Studies have demonstrated that adding brexpiprazole to an antidepressant led to a statistically significant reduction in depression scores, such as those measured by the Montgomery Åsberg Depression Rating Scale (MADRS), when compared to adding a placebo. These trials involved patients who had not fully responded to at least one prior antidepressant treatment, underscoring brexpiprazole’s role in addressing persistent symptoms.
Potential Side Effects and Safety Information
As with any medication, brexpiprazole can cause side effects, and patients should be aware of these possibilities. Common side effects reported in clinical trials include weight gain, a feeling of inner restlessness or jitteriness known as akathisia, and somnolence or sleepiness. Other frequently observed effects might include headaches. These effects can vary in intensity among individuals, and their occurrence can sometimes be dose-dependent.
It is important to understand the serious safety information associated with brexpiprazole, which includes a boxed warning from the FDA. This warning highlights an increased risk of suicidal thoughts and behaviors in children, adolescents, and young adults aged 24 and younger when taking antidepressants and similar medications. Another significant warning concerns elderly patients with dementia-related psychosis, as atypical antipsychotics like brexpiprazole can increase the risk of death in this population. Patients and caregivers should closely monitor for any changes in mood or behavior, especially during the initial weeks of treatment or following dose adjustments.
Further significant warnings include the potential for metabolic changes, such as increases in blood sugar levels, which can sometimes lead to diabetes, and changes in cholesterol and triglyceride levels. There is also a possibility of developing compulsive behaviors, such as gambling, excessive shopping, or hypersexuality. Other less common but serious risks include neuroleptic malignant syndrome, a rare but life-threatening neurological disorder, and tardive dyskinesia, which involves involuntary movements, particularly of the face and tongue. Individuals should have a thorough discussion with their healthcare provider about all potential risks and benefits before starting treatment.