What is the appropriate starting dose, contraindications, and monitoring recommendations for initiating Auvelity (dextromethorphan‑bupropion) in an adult with major depressive disorder?

Auvelity (Dextromethorphan-Bupropion) for Major Depressive Disorder

Starting Dose and Titration

Start Auvelity at one tablet (45 mg dextromethorphan/105 mg bupropion) once daily in the morning for 3 days, then increase to one tablet twice daily (separated by at least 8 hours) as the maintenance dose. 1

• Swallow tablets whole; do not crush, divide, or chew 1
• Can be taken with or without food 1
• Do not exceed two doses within the same day 1

Absolute Contraindications

Auvelity is contraindicated in the following situations 1:

• Seizure disorder (current or history)
• Bulimia or anorexia nervosa (current or prior diagnosis) - higher seizure incidence observed with bupropion
• Abrupt discontinuation of alcohol, benzodiazepines, barbiturates, or antiepileptic drugs - increases seizure risk
• MAOI use within 14 days (or starting MAOI within 14 days of stopping Auvelity) - risk of hypertensive crisis and serotonin syndrome
• Known hypersensitivity to bupropion or dextromethorphan - anaphylaxis and Stevens-Johnson syndrome reported

Mandatory Pre-Treatment Screening

Before initiating Auvelity, you must 1:

• Assess blood pressure and monitor periodically during treatment (hypertension risk)
• Screen for personal or family history of bipolar disorder, mania, or hypomania (risk of manic activation)
• Verify patient is not taking other bupropion or dextromethorphan products (avoid duplication/overdose)
• Screen for suicidal ideation given black box warning for increased suicidal thoughts in patients ≤24 years old

Monitoring Recommendations

Begin monitoring within 1-2 weeks of initiation and continue regularly, particularly during the first 1-2 months when suicide risk is highest. 2

Monitor for 2, 1:

• Suicidal thoughts and behaviors - especially in younger adults
• Agitation, irritability, or unusual behavioral changes - may indicate worsening depression
• Blood pressure - assess periodically throughout treatment 1
• Therapeutic response - assess at 6-8 weeks; modify treatment if inadequate response 2

Dose Adjustments for Special Populations

Moderate renal impairment (eGFR 30-59 mL/min/1.73 m²): One tablet once daily in the morning only 1

CYP2D6 poor metabolizers: One tablet once daily in the morning only 1

Concomitant strong CYP2D6 inhibitors: One tablet once daily in the morning only 1

Common Adverse Effects

The most frequent adverse events are 1, 3, 4:

• Dizziness, nausea, headache (most common)
• Somnolence, dry mouth, diarrhea
• Hyperhidrosis, anxiety, constipation
• Decreased appetite, insomnia
• Most adverse events are mild-to-moderate in severity 5

Notable advantages: Not associated with psychotomimetic effects, weight gain, or increased sexual dysfunction 3, 6

Clinical Efficacy Context

Auvelity demonstrated rapid onset of antidepressant effect, with significant improvement observed at week 1 and maintained through week 6 3, 5. Remission rates of 39.5-46.5% were achieved compared to 16.2-17.3% with placebo/bupropion alone 3, 6, 7. In real-world practice, 28.8% of patients initiated Auvelity as monotherapy, while 71.2% used it as add-on therapy, most commonly with SSRIs or SNRIs 8.

Treatment Duration

Continue treatment for 4-9 months after satisfactory response in first-episode MDD; for patients with ≥2 episodes, longer duration (years to lifelong) may be beneficial. 2