What antipsychotic medication can be added to Rexulti (brexpiprazole)?

From the Guidelines

When adding an antipsychotic to Rexulti (brexpiprazole), aripiprazole is a commonly considered option, as it has been shown to be effective in reducing treatment side effects or residual symptoms when combined with other antipsychotics, such as clozapine, and this may also hold true for combining it with brexpiprazole, although more research is needed to confirm this 1. Several antipsychotic medications can be added to Rexulti in certain clinical situations, though this approach requires careful consideration.

• Commonly used options include low-dose aripiprazole, quetiapine, olanzapine, or risperidone.
• When adding a second antipsychotic, it's typically best to start with a low dose, such as quetiapine 25-50mg daily or risperidone 0.5-1mg daily, and titrate slowly based on response and side effects. This combination therapy should generally be considered a short-term strategy while transitioning between medications or addressing acute symptom exacerbation, rather than a long-term solution. The rationale for combining antipsychotics includes targeting different receptor profiles to address specific symptoms that aren't responding to Rexulti alone. However, this approach increases the risk of side effects, including metabolic issues, extrapyramidal symptoms, and QTc prolongation. Regular monitoring of vital signs, metabolic parameters, and movement disorders is essential. Before adding another antipsychotic, ensure Rexulti has been optimized at an adequate dose for sufficient duration, and consider consulting with a psychiatrist to evaluate the risk-benefit ratio for the individual patient, as antipsychotic polypharmacy may be associated with a reduced risk of psychiatric hospitalization and all-cause mortality, as shown in some studies 1. It is also important to note that treatment guidelines mainly recommend antipsychotic monotherapy, but antipsychotic polypharmacy is widely used in clinical practice, with a median rate of 19.6% in outpatients with schizophrenia, and up to 40% in inpatients, and the use of two concurrent antipsychotics is the most prevalent number of concurrent antipsychotics when using antipsychotic polypharmacy 1.

From the Research

Antipsychotic Medication to be Added to Rexulti

There are no specific studies that recommend adding another antipsychotic medication to Rexulti (brexpiprazole). However, the following points can be considered:

• Brexpiprazole is a serotonin-dopamine activity modulator with a unique receptor binding profile and low intrinsic D2 activity, which suggests a lower potential to cause activation-like adverse effects compared to other antipsychotics 2.
• The medication has been approved for the treatment of schizophrenia and as an adjunctive treatment in major depressive disorder 3.
• Brexpiprazole has a more tolerable side effect profile with regard to akathisia, extrapyramidal dysfunction, and sedation compared to other antipsychotics, such as aripiprazole 4.

Potential Antipsychotic Medications

Some potential antipsychotic medications that could be considered for addition to Rexulti include:

• Aripiprazole: Although brexpiprazole has a lower potential to cause activation-like adverse effects, aripiprazole could be considered for addition to Rexulti in certain cases.
• Cariprazine: This medication has a similar mechanism of action to brexpiprazole and could be considered as an alternative or addition to Rexulti.
• Ziprasidone: This medication has a different mechanism of action compared to brexpiprazole and could be considered as an addition to Rexulti in certain cases.

Important Considerations

When considering adding another antipsychotic medication to Rexulti, the following points should be taken into account:

• The potential for increased adverse effects, such as extrapyramidal symptoms, hyperprolactinemia, and weight gain.
• The potential for interactions between the medications, including changes in pharmacokinetics and pharmacodynamics.
• The need for careful monitoring of the patient's response to the addition of another antipsychotic medication, including regular assessments of efficacy and tolerability 5, 6.