Can Seroquel (quetiapine) and Rexulti (brexpiprazole) be mixed?

Mixing Seroquel (Quetiapine) and Rexulti (Brexpiprazole)

Combining Seroquel (quetiapine) and Rexulti (brexpiprazole) should generally be avoided as this constitutes antipsychotic polytherapy, which guidelines recommend against due to increased risk of adverse effects without clear evidence of superior efficacy.

Rationale Against Combination

According to clinical guidelines, using multiple antipsychotics simultaneously is not recommended as first-line practice:

• The WHO guidelines explicitly state that "routinely, one antipsychotic should be prescribed at a time" 1. Antipsychotic combination treatment should only be considered for individuals who do not respond to single antipsychotic therapy, and even then preferably under the supervision of mental health professionals with close clinical monitoring.

• Polypharmacy with multiple antipsychotics increases the risk of:

  • Additive side effects
  • Drug-drug interactions
  • Medication errors
  • Reduced adherence due to complex regimens
  • Higher overall medication burden

Pharmacological Considerations

Both medications are antipsychotics but work through somewhat different mechanisms:

• Quetiapine (Seroquel) is a dibenzothiazepine atypical antipsychotic that acts as an antagonist at multiple neurotransmitter receptors including serotonin 5-HT2A and dopamine D2 receptors 2.

• Brexpiprazole (Rexulti) is a newer atypical antipsychotic that acts as a partial agonist at dopamine D2 receptors and serotonin 5-HT1A receptors, and as an antagonist at 5-HT2A receptors.

The combination may lead to:

• Excessive dopamine D2 receptor blockade, increasing risk of extrapyramidal symptoms
• Additive sedation and orthostatic hypotension
• QT interval prolongation concerns
• Metabolic side effects (weight gain, hyperglycemia, dyslipidemia)

Exceptions and Special Circumstances

In rare cases where combination therapy might be considered:

1. Treatment-resistant schizophrenia or other psychotic disorders where monotherapy with multiple agents has failed
2. Cross-titration periods (when switching from one antipsychotic to another)
3. Under close supervision of a psychiatrist with expertise in psychopharmacology

Even in these cases, the combination should be:

• Temporary if possible
• Closely monitored for adverse effects
• Regularly reassessed for continued necessity

Monitoring If Combination Is Used

If the combination is deemed necessary by a psychiatrist, monitoring should include:

• Regular assessment of extrapyramidal symptoms
• Metabolic parameters (weight, blood glucose, lipids)
• Cardiovascular monitoring (blood pressure, heart rate, ECG for QT interval)
• Sedation and cognitive effects
• Overall psychiatric symptoms and functioning

Alternative Approaches

Instead of combining these medications, consider:

1. Optimizing the dose of a single antipsychotic
2. Switching to a different antipsychotic with a better efficacy/side effect profile for the individual
3. Augmentation with a non-antipsychotic medication (mood stabilizer, antidepressant) if clinically indicated
4. Clozapine for treatment-resistant cases (under appropriate monitoring)

In conclusion, while there may be specific clinical scenarios where combining quetiapine and brexpiprazole might be considered, this approach should not be routine practice and should only be implemented under specialist psychiatric supervision with careful monitoring for adverse effects.