Can Auvelity (dextromethorphan‑bupropion) be combined with Vyvanse (lisdexamfetamine) in a patient with major depressive disorder and attention‑deficit/hyperactivity disorder, and what are the safety concerns and monitoring recommendations?

Combining Auvelity and Vyvanse: Safety and Monitoring

Auvelity (dextromethorphan-bupropion) can be safely combined with Vyvanse (lisdexamfetamine) in patients with comorbid major depressive disorder and ADHD, as there are no significant pharmacokinetic interactions between these medications, and this combination addresses both conditions through complementary mechanisms. 1

Pharmacologic Rationale for Combination Therapy

• No major drug-drug interactions exist between the bupropion component of Auvelity and amphetamine-based stimulants like Vyvanse; these agents can be prescribed concurrently without dose adjustments for pharmacokinetic reasons. 1

• The combination is mechanistically sound: Vyvanse addresses ADHD through dopamine and norepinephrine enhancement, while Auvelity targets depression via NMDA receptor antagonism (dextromethorphan) and additional norepinephrine/dopamine reuptake inhibition (bupropion). 2, 3

• Stimulants achieve 70-80% response rates for ADHD with effects observable within days, allowing rapid assessment of ADHD symptom control before evaluating the antidepressant response from Auvelity. 1

• Auvelity demonstrates significantly faster onset of antidepressant effect (within 2 weeks) compared to traditional SSRIs, with sustained efficacy through 12-15 months of treatment and remission rates approaching 70%. 3

Treatment Sequencing Algorithm

When both conditions require treatment:

1. Initiate Vyvanse first at 20-30 mg once daily in the morning, titrating by 10 mg weekly up to 70 mg maximum, to establish ADHD symptom control. 1

2. Assess ADHD response after 6-8 weeks of optimized stimulant dosing; if depressive symptoms persist despite ADHD improvement, add Auvelity. 1

3. Start Auvelity at 1 tablet (dextromethorphan 45 mg/bupropion 105 mg) once daily in the morning for 3 days, then increase to 1 tablet twice daily (morning and afternoon). 2, 3

4. Avoid late-day Auvelity dosing to minimize insomnia risk, particularly given the stimulant component from Vyvanse. 4

Critical Safety Monitoring

Cardiovascular Parameters

• Measure blood pressure and pulse at baseline and every visit during titration, as both medications can elevate these parameters independently. 1, 5

• Avoid this combination in patients with uncontrolled hypertension or symptomatic cardiovascular disease. 4, 1

Seizure Risk

• Bupropion lowers seizure threshold; the combination of Auvelity (containing 105 mg bupropion per tablet, 210 mg daily at maintenance dose) plus stimulants may theoretically increase seizure risk, though this is not well-documented. 4, 1

• Avoid in patients with epilepsy or history of seizures, and use extreme caution in those with clinical factors that increase seizure risk (eating disorders, abrupt benzodiazepine/alcohol withdrawal, head trauma). 4

Psychiatric Monitoring

• Screen for suicidal ideation at every visit, particularly during the first few months or at dose changes, as both Auvelity and stimulants carry warnings about psychiatric adverse effects. 1, 6

• Monitor for activation symptoms (agitation, anxiety, insomnia, irritability) that may emerge from the combined stimulant effects of Vyvanse and the bupropion component of Auvelity. 1, 6

Common Adverse Effects

• Most frequent side effects of Auvelity include dizziness, nausea, headache, diarrhea, somnolence, dry mouth, sexual dysfunction, hyperhidrosis, anxiety, constipation, decreased appetite, and insomnia. 6

• Appetite suppression and insomnia may be additive when combining these medications; monitor weight at each visit and address sleep hygiene proactively. 1, 6

Absolute Contraindications

• Never combine with MAO inhibitors or initiate within 14 days of MAOI discontinuation due to risk of hypertensive crisis. 1, 5

• Active psychosis or uncontrolled mania contraindicates stimulant use. 1

• Prior hypersensitivity to amphetamines or bupropion is an absolute contraindication. 1

Dosing Considerations

• Maximum Vyvanse dose is 70 mg daily; typical therapeutic range is 30-70 mg once in the morning. 1

• Auvelity maintenance dose is 1 tablet twice daily (total daily: dextromethorphan 90 mg/bupropion 210 mg); do not exceed this dose. 2, 3

• Total daily bupropion exposure from Auvelity (210 mg) is below the 450 mg maximum but should be considered when evaluating seizure risk. 4

Follow-Up Schedule

• Weekly contact during initial titration to assess ADHD symptom response, mood changes, and adverse effects. 1

• Monthly visits for the first 3-4 months to monitor cardiovascular parameters, weight, mood symptoms, and ADHD control. 5

• Quarterly visits once stable, with ongoing assessment of functional improvement across work, social, and personal domains. 1

Common Pitfalls to Avoid

• Do not assume Auvelity alone will treat both ADHD and depression; no single antidepressant (including bupropion-containing combinations) is proven effective for both conditions, and stimulants remain first-line for ADHD. 1

• Do not delay ADHD treatment while addressing depression first unless the mood disorder presents with severe features (psychosis, suicidality); untreated ADHD perpetuates functional impairment even after mood improvement. 1

• Do not overlook the rapid onset of Auvelity (2 weeks) compared to traditional antidepressants (4-6 weeks); reassess depressive symptoms earlier than you would with SSRIs. 3, 7

• Do not prescribe this combination without capacity for close monitoring; the additive stimulant effects, seizure risk, and cardiovascular concerns require systematic follow-up. 4, 1