What is the optimal combination of Rexulti (brexpiprazole) with Selective Serotonin Reuptake Inhibitors (SSRIs) for treatment?

From the Guidelines

Rexulti (brexpiprazole) works best with sertraline, given its favorable pharmacokinetic profile and lower transfer to breast milk, making it a preferred SSRI for combination therapy, especially in patients who require adjunctive treatment for major depressive disorder. When combining Rexulti with an SSRI, the optimal approach typically involves adding 0.5-3 mg of Rexulti daily to an established SSRI regimen, with treatment usually beginning with 0.5-1 mg of Rexulti daily and gradual increases of 0.5-1 mg at weekly intervals as needed, not exceeding 3 mg daily 1. Common SSRI partners include fluoxetine, sertraline, escitalopram, and paroxetine at their standard therapeutic doses. This adjunctive approach is most effective after patients have been on an adequate dose of an SSRI for at least 6-8 weeks with partial or insufficient response. The combination works by complementing the serotonergic effects of SSRIs with Rexulti's partial agonism at serotonin 5-HT1A receptors and antagonism at 5-HT2A receptors, while also modulating dopamine through partial D2 receptor agonism.

Some key points to consider when combining Rexulti with SSRIs include:

• Starting with a low dose of Rexulti and gradually increasing as needed and tolerated
• Monitoring patients for potential side effects, including akathisia, weight gain, and metabolic changes, particularly during the first few weeks of combination therapy
• Continuing the combination for at least 6 months after symptom improvement to prevent relapse
• Selecting an SSRI with a favorable profile, such as sertraline, which has lower transfer to breast milk and is generally well-tolerated 1.

It's essential to weigh the benefits and risks of combination therapy and to individualize treatment based on patient-specific factors, including medical history, current medications, and personal preferences.

From the FDA Drug Label

In two 6-week double-blind, placebo-controlled, fixed-dose studies of adult patients meeting DSM-IV-TR criteria for MDD, with or without symptoms of anxiety, who had an inadequate response to prior antidepressant therapy (1 to 3 courses) in the current episode and who had also demonstrated an inadequate response throughout the 8 weeks of prospective antidepressant treatment (with escitalopram, fluoxetine, paroxetine controlled-release, sertraline, duloxetine delayed-release, or venlafaxine extended-release)

The FDA drug label does not specify which SSRI works best with Rexulti (brexpiprazole). However, it does mention that brexpiprazole was studied as an adjunctive treatment to several SSRIs, including escitalopram, fluoxetine, paroxetine, sertraline, as well as other antidepressants like duloxetine and venlafaxine.

• The studies showed that brexpiprazole was effective in reducing depressive symptoms when used in combination with these antidepressants.
• However, the label does not provide a direct comparison of the efficacy of brexpiprazole with different SSRIs.
• Therefore, the choice of SSRI to use with brexpiprazole should be based on individual patient factors and clinical judgment 2.

From the Research

Optimal Combination of Rexulti with SSRIs

There is limited information available on the optimal combination of Rexulti (brexpiprazole) with Selective Serotonin Reuptake Inhibitors (SSRIs) for treatment. However, based on the available studies, here are some key points to consider:

• Brexpiprazole is a serotonin-dopamine activity modulator that has been approved for the treatment of schizophrenia and as an adjunctive therapy for major depressive disorder (MDD) 3, 4.
• The drug has a unique receptor binding profile, with partial agonist activity at dopamine D2 and serotonin 5-HT1A receptors, and antagonist activity at serotonin 5-HT2A receptors 5, 6.
• In clinical trials, brexpiprazole has been shown to be effective in improving depressive symptoms in adults with MDD who have had an incomplete response to previous treatment with antidepressants, including SSRIs 3.
• The most commonly used SSRIs in combination with brexpiprazole are not specified in the available studies, but the drug has been shown to be effective in combination with antidepressant therapy (ADT) in general 3.
• The optimal dosage of brexpiprazole when used in combination with SSRIs is also not specified, but the drug has been shown to be effective at doses of 2-4 mg/day in the treatment of schizophrenia and MDD 5, 3.

Key Considerations

Some key considerations when using brexpiprazole in combination with SSRIs include:

• The potential for increased risk of serotonin syndrome, a potentially life-threatening condition caused by excessive levels of serotonin in the body 4.
• The potential for increased risk of extrapyramidal symptoms, such as akathisia, dystonia, and parkinsonism, although brexpiprazole has been shown to have a lower risk of these symptoms compared to other antipsychotics 5, 6.
• The potential for increased risk of metabolic abnormalities, such as weight gain, hyperlipidemia, and hyperglycemia, although brexpiprazole has been shown to have a lower risk of these abnormalities compared to other antipsychotics 5, 6.

Available Data

Based on the available data, it appears that brexpiprazole can be used effectively in combination with SSRIs for the treatment of MDD and schizophrenia, but the optimal combination and dosage have not been fully established 5, 3, 4, 7, 6.