What is the recommended treatment protocol for Auvelity (dextromethorphan-bupropion) in adults with major depressive disorder?

From the Guidelines

The recommended treatment protocol for Auvelity in adults with major depressive disorder begins with 45 mg dextromethorphan/105 mg bupropion once daily in the morning for the first three days, then increases to the maintenance dose of 45 mg dextromethorphan/105 mg bupropion twice daily, taken at least 8 hours apart. Patients should swallow the tablets whole without crushing or chewing them, and can take them with or without food. The full antidepressant effect may take several weeks to develop, so patients should continue treatment even if they don't notice immediate improvement. Dose adjustments are necessary for patients with moderate renal impairment (reduce to once daily) and for those taking CYP2D6 inhibitors. Auvelity should not be used in patients with seizure disorders, bulimia/anorexia nervosa, during abrupt discontinuation of alcohol or sedatives, or in those taking MAOIs. The medication works through a novel mechanism combining NMDA receptor antagonism (dextromethorphan) and dopamine/norepinephrine reuptake inhibition (bupropion), providing a faster onset of action than traditional antidepressants for many patients.

Some key points to consider when treating patients with Auvelity include:

• Monitoring patient status, therapeutic response, and adverse effects of antidepressant therapy on a regular basis beginning within 1 to 2 weeks of initiation of therapy 1
• Modifying treatment if the patient does not have an adequate response to pharmacotherapy within 6 to 8 weeks of the initiation of therapy for major depressive disorder 1
• Continuing treatment for 4 to 9 months after a satisfactory response in patients with a first episode of major depressive disorder, and considering an even longer duration of therapy for patients who have had 2 or more episodes of depression 1
• Discussing adverse event profiles with patients before selecting a medication, as differences have been reported among some medications in mild to major adverse effects 1

Overall, the treatment of major depressive disorder with Auvelity should be individualized and based on a thorough assessment of the patient's symptoms, medical history, and treatment goals.

From the Research

Treatment Protocol for Auvelity

The recommended treatment protocol for Auvelity (dextromethorphan-bupropion) in adults with major depressive disorder is as follows:

• The medication is approved for the treatment of major depressive disorder in adults 2
• Auvelity is an extended-release fixed combination of dextromethorphan and bupropion 2
• The combination of bupropion and dextromethorphan can be used as a first-line therapy, as a second option when a patient has failed to achieve remission with a serotonin-targeting agent, and for treatment-resistant depression 3

Dosage and Administration

• The dosage of Auvelity is 45-105 mg, with significant reductions in Montgomery-Åsberg Depression Rating Scale total scores compared to placebo 4
• Changes in Montgomery-Åsberg Depression Rating Scale scores with dextromethorphan-bupropion were seen within two weeks in both clinical trials 4
• Remission and response rates were significantly higher with dextromethorphan-bupropion in both studies 4

Safety and Tolerability

• The medication was well-tolerated in both trials, with the most common adverse events being rated as mild-to-moderate 4
• The most common adverse effects of dextromethorphan-bupropion include dizziness, nausea, headache, diarrhea, somnolence, dry mouth, sexual dysfunction, hyperhidrosis, anxiety, constipation, decreased appetite, and insomnia 2
• Auvelity carries a boxed warning that it may increase the risk of suicidal thoughts and behaviors in pediatric and young adult patients 2
• Seizures can also occur and are more likely at higher doses 2

Real-World Treatment Patterns

• A real-world analysis of 22,288 patients with major depressive disorder treated with Auvelity in the United States found that 10.1% were treatment-naïve and 28.8% initiated Auvelity as monotherapy 5
• Most patients had mental health-related comorbidities and attempted various MDD-related treatments prior to Auvelity 5