Can low dose Adderall (amphetamine and dextroamphetamine) be used with Rexulti (brexpiprazole)?

Combining Low-Dose Adderall with Rexulti (Brexpiprazole)

Low-dose Adderall can be safely combined with Rexulti (brexpiprazole), particularly in patients with treatment-resistant ADHD who have failed multiple stimulant trials, though this combination requires careful monitoring for cardiovascular effects and should be reserved for specific clinical scenarios. 1

Evidence for Combination Therapy

The most relevant controlled trial specifically examined brexpiprazole augmentation of stimulant therapy in adults with treatment-resistant ADHD. This study demonstrated that brexpiprazole combined with stimulants was well-tolerated, with adverse effects equivalent between brexpiprazole and placebo groups. 1 The combination showed particular promise for patients who had previously failed two or more stimulant trials, especially for managing emotional dysregulation symptoms that often accompany ADHD. 1

Clinical Scenarios Where Combination is Appropriate

Treatment-Resistant ADHD

• Use brexpiprazole augmentation specifically in patients who have failed adequate trials of at least two different stimulants at therapeutic doses. 1
• The combination targets both core ADHD symptoms (via stimulant) and emotional dysregulation (via brexpiprazole). 1

Comorbid Bipolar Disorder with ADHD

• Stabilize mood symptoms first with a mood stabilizer before adding stimulants. 2
• A randomized controlled trial demonstrated that low-dose mixed amphetamine salts (starting at 5-10 mg daily) were safe and effective for treating comorbid ADHD once mood symptoms were stabilized with divalproex. 2
• Atypical antipsychotics like brexpiprazole serve as mood stabilizers in bipolar disorder, making this combination particularly rational for dual diagnosis patients. 2

Dosing Strategy

Starting Doses

• Begin Adderall at 5 mg once or twice daily (total 5-10 mg/day). 2
• Start brexpiprazole at the lowest available dose (typically 0.5-1 mg daily) and titrate slowly. 1

Titration Schedule

• Increase Adderall by 5 mg increments weekly based on symptom response and tolerability. 2
• Maximum daily Adderall dose should generally not exceed 40 mg in adults, though some patients may require up to 50 mg when covering a longer day. 2
• For patients under 25 kg, maximum daily Adderall dose should not exceed 35 mg. 2

Critical Monitoring Requirements

Cardiovascular Surveillance

• Check blood pressure and pulse at baseline and with each dose adjustment. 2
• Amphetamines cause α-adrenergic vasoconstriction and β-adrenergic increases in heart rate and stroke volume. 2, 3
• Monitor for hypertension, tachycardia, and arrhythmias, which are the primary cardiovascular risks. 3

Neuropsychiatric Monitoring

• Assess for excessive stimulation, agitation, anxiety, paranoia, or psychosis at each visit. 3
• While brexpiprazole may theoretically attenuate some stimulant-induced agitation through D2 partial agonism, vigilance is still required. 4
• Monitor for serotonin syndrome if other serotonergic agents are co-prescribed, as stimulants (particularly amphetamines) have serotonergic activity. 2

Metabolic and Physical Parameters

• Weigh patient at each visit to monitor for appetite suppression and weight loss. 2
• Check height in children and adolescents, as stimulants can affect growth. 2

Drug Interaction Considerations

Contraindicated Combinations

• Never combine with MAOIs or within 14 days of MAOI discontinuation due to severe hypertension and serotonin syndrome risk. 2
• Avoid concurrent use of multiple stimulants, as this significantly increases risk of severe hypertension and psychosis. 5

Caution with Other Medications

• Limit caffeine intake to <200 mg daily (approximately 2 cups of coffee) to minimize additive cardiovascular effects. 2, 6
• Avoid decongestants (phenylephrine, pseudoephedrine) which add to sympathomimetic burden. 2
• Exercise caution with other serotonergic drugs (SSRIs, SNRIs, tramadol, dextromethorphan) due to serotonin syndrome risk. 2

Management of Adverse Effects

Cardiovascular Toxicity

• For severe hypertension or tachycardia, use benzodiazepines as first-line treatment. 3
• Consider α-blocking agents or calcium channel blockers for severe vasoconstriction. 6
• Avoid β-blockers, which may worsen vasoconstriction through unopposed α-adrenergic effects. 6

CNS Overstimulation

• Use benzodiazepines for agitation, tremor, or anxiety. 3
• If benzodiazepines are insufficient, consider antipsychotics (ziprasidone, haloperidol), dexmedetomidine, or propofol for severe cases. 3
• The brexpiprazole component may provide some protection against stimulant-induced agitation through D2 partial agonism. 4

Insomnia

• Time the last Adderall dose no later than 2:00 PM to minimize sleep disruption. 6
• Consider switching to once-daily morning dosing if insomnia persists. 2

Common Pitfalls to Avoid

• Do not add brexpiprazole if the patient has not had adequate trials of at least two different stimulants at therapeutic doses. 5, 1
• Do not use this combination as first-line therapy for uncomplicated ADHD. 1
• Do not exceed maximum recommended Adderall doses (40-50 mg daily in adults) even when combined with brexpiprazole. 2, 5
• Do not neglect cardiovascular monitoring, as amphetamines increase both α- and β-adrenergic activity. 3
• Do not combine with other stimulants, as this dramatically increases toxicity risk. 5

Special Populations

Patients with Cardiovascular Disease

• Use extreme caution or avoid stimulants entirely in patients with pre-existing hypertension, arrhythmias, or structural heart disease. 2
• Consider non-stimulant ADHD medications (atomoxetine, guanfacine, clonidine) as safer alternatives. 3

Pediatric Patients

• The combination of stimulants with atypical antipsychotics is common in pediatric bipolar disorder with comorbid ADHD. 2
• Ensure mood stabilization before introducing stimulants in bipolar youth. 2
• Monitor growth parameters (height, weight) more closely in children. 2

Duration of Treatment

• Maintain the regimen that stabilized acute symptoms for 12-24 months before considering dose reduction. 2
• Some patients with treatment-resistant ADHD or comorbid bipolar disorder may require lifelong therapy when benefits outweigh risks. 2
• Reassess need for continuation on a case-by-case basis, weighing symptom control against adverse effects. 2