Can Rexulti Be Taken With Vyvanse?
Yes, Rexulti (brexpiprazole) can be taken together with Vyvanse (lisdexamfetamine), and this combination is explicitly supported in clinical practice guidelines for treating multiple co-occurring psychiatric conditions.
Rationale for Combination Therapy
The combination of an atypical antipsychotic (Rexulti) with a stimulant (Vyvanse) is a recognized and guideline-supported approach when treating patients with multiple psychiatric disorders. The AACAP practice parameter explicitly states that medication combinations are appropriate "to treat multiple disorders in the same patient (e.g., a stimulant and an SSRI for ADHD and anxiety or an antipsychotic and an SSRI for tics and OCD)" 1. While this specific example mentions SSRIs, the principle directly applies to combining stimulants with antipsychotics when clinically indicated.
Clinical Evidence Supporting This Combination
Recent research specifically examined brexpiprazole combined with stimulants in treatment-resistant ADHD. A 2022 controlled study augmented stimulant therapy (including lisdexamfetamine) with brexpiprazole in adults who failed initial stimulant treatment 2. While the primary outcome showed no drug-placebo differences, the study demonstrated:
- Safety profile: Adverse effects on brexpiprazole plus stimulant were equivalent to placebo
- Potential benefit: Trends toward improvement in emotional dysregulation symptoms in prior stimulant nonresponders
- Tolerability: The combination was well-tolerated without significant safety concerns
Drug Interaction Profile
The FDA label for Rexulti does not list any contraindications or significant interactions with stimulants like Vyvanse 3. The drug interaction section focuses on:
- CYP3A4 inhibitors/inducers
- CYP2D6 inhibitors
- No mention of stimulants as problematic combinations
Importantly, the label states that "no dosage adjustment for substrates of CYP2D6, CYP3A4, CYP2B6, BCRP, or P-gp is required when administered concomitantly with REXULTI" 3. Lisdexamfetamine is not metabolized through pathways that would interact with brexpiprazole's metabolism.
Common Clinical Scenarios for This Combination
This combination would be appropriate when treating:
- Schizophrenia with comorbid ADHD: Using Vyvanse for ADHD symptoms and Rexulti for psychotic symptoms
- Treatment-resistant depression with ADHD: Rexulti as augmentation for depression plus Vyvanse for ADHD
- Treatment-resistant ADHD: Brexpiprazole augmentation when stimulants alone are insufficient, particularly for emotional dysregulation 2
Monitoring Considerations
When combining these medications, monitor for:
- Cardiovascular effects: Both medications can affect heart rate and blood pressure
- Weight and metabolic parameters: Rexulti can cause weight gain and metabolic changes 3
- Psychiatric symptoms: Watch for worsening agitation, psychosis, or mood symptoms
- Sleep disturbances: Stimulants can cause insomnia; timing of doses matters
Important Caveats
- Develop a clear treatment plan: Before combining medications, establish specific target symptoms for each agent and a monitoring plan 1
- Avoid polypharmacy without rationale: The combination should address distinct symptom domains or disorders, not simply "cover all bases" 1
- Consider timing: Vyvanse is typically dosed in the morning; Rexulti can be taken once daily with or without food 3
- Substance abuse screening: In adolescents or those with substance use history, monitor for stimulant diversion 4
The combination of Rexulti and Vyvanse is pharmacologically safe and clinically appropriate when there is a clear rationale for treating multiple psychiatric conditions or symptom domains simultaneously.