Can Rexulti (brexpiprazole) be taken with Caplyta (lumateperone)?

Concomitant Use of Rexulti (Brexpiprazole) and Caplyta (Lumateperone)

Yes, Rexulti (brexpiprazole) and Caplyta (lumateperone) can be taken together, as there are no known significant drug interactions between these two atypical antipsychotics.

Pharmacological Profiles and Mechanisms of Action

These medications work through different but complementary mechanisms:

• Rexulti (brexpiprazole):

  • Partial agonist at dopamine D2 and serotonin 5-HT1A receptors
  • Antagonist at serotonin 5-HT2A receptors
  • Has lower intrinsic activity at D2 receptors compared to similar agents like aripiprazole
  • Demonstrates a lower propensity for activating adverse events and extrapyramidal symptoms 1

• Caplyta (lumateperone):

  • Potent antagonist at serotonin 5-HT2A receptors
  • Brief binding to dopamine D1 and D2 receptors
  • Partial agonism at presynaptic D2 receptors
  • Indirect modulation of NMDA and AMPA glutamate receptors 2

Clinical Considerations

When combining these medications, consider:

1. Therapeutic Rationale:

   • The combination may provide broader receptor coverage
   • May be beneficial for patients with incomplete response to a single antipsychotic
   • Different receptor profiles may address different symptom domains

2. Monitoring Parameters:

   • Weight and metabolic parameters (both can cause moderate weight gain)
   • Extrapyramidal symptoms (though both have relatively low risk)
   • QT interval changes
   • Overall tolerability and efficacy

3. Dosing Considerations:

   • Start with lower doses of each medication when using in combination
   • Titrate gradually based on response and tolerability
   • Consider the approved dosing ranges for each medication individually

Potential Advantages of the Combination

• Brexpiprazole has shown efficacy for both positive and negative symptoms in schizophrenia 3
• Lumateperone's unique mechanism with glutamatergic modulation may complement brexpiprazole's action
• Brexpiprazole has demonstrated pro-cognitive effects in preclinical studies 4

Potential Concerns

• Additive sedation may occur
• Potential for additive weight gain or metabolic effects
• Cost considerations (both are relatively newer antipsychotics)
• Limited clinical data on this specific combination

Clinical Approach

1. Establish baseline:

   • Document current symptoms and severity
   • Obtain baseline weight, metabolic parameters, and ECG

2. Initiate therapy:

   • Consider starting one medication first and stabilizing before adding the second
   • Begin with lower doses of each medication

3. Regular monitoring:

   • Follow up within 2-4 weeks of initiating combination
   • Monitor for efficacy and adverse effects
   • Adjust doses as needed based on response

While there are no formal drug interaction studies specifically examining this combination, the different pharmacological profiles suggest they can be used together when clinically indicated. As with any medication combination, careful monitoring for efficacy and side effects is essential.