What is the recommended treatment regimen for an adult patient with major depressive disorder using Auvelity (dextromethorphan-bupropion)?

Auvelity Treatment Regimen for Major Depressive Disorder

Dosing and Initiation

Auvelity (dextromethorphan-bupropion) should be initiated at 45-105 mg daily for adults with major depressive disorder, with clinical response expected within 2 weeks of treatment initiation. 1

Starting Regimen

• Begin Auvelity at the standard dose of dextromethorphan 45 mg combined with bupropion 105 mg 1
• The medication can be used as first-line monotherapy, as second-line treatment after inadequate response to SSRIs/SNRIs, or as add-on therapy to existing antidepressants 2, 3
• Real-world data shows 28.8% of patients initiate Auvelity as monotherapy, while 71.2% use it as add-on therapy, most commonly with SSRIs (10.7%) or SNRIs (6.5%) 3

Treatment Duration and Monitoring

Continue treatment for 4-9 months after achieving satisfactory response in first-episode depression, and longer for patients with two or more prior depressive episodes. 4

Monitoring Schedule

• Assess patients within 1-2 weeks of therapy initiation to evaluate early response 4
• Evaluate treatment response at 6-8 weeks; if inadequate improvement occurs, modify treatment strategy 4
• Monitor for adverse effects, which are typically mild-to-moderate in severity 1

Expected Timeline

• Significant reductions in Montgomery-Åsberg Depression Rating Scale (MADRS) scores occur within 2 weeks, distinguishing Auvelity from traditional antidepressants that require 4-6 weeks 1, 5
• Long-term studies demonstrate sustained efficacy through 12-15 months of treatment 1
• Remission rates approach 70% and response rates exceed 80% in long-term treatment 1

Clinical Positioning

When to Use Auvelity

• First-line option: Can be initiated as monotherapy in treatment-naïve patients (10.1% of real-world users were treatment-naïve) 3
• Second-line option: After inadequate response to SSRIs or SNRIs (83.7% of patients had prior SSRI, SNRI, or bupropion treatment) 3
• Treatment-resistant depression: Appropriate for patients who have failed multiple antidepressant trials 2, 5

Mechanism and Rationale

• Dextromethorphan modulates glutamatergic signaling through NMDA receptor antagonism and sigma-1 receptor agonism 1
• Bupropion inhibits CYP2D6, increasing dextromethorphan bioavailability while providing additional norepinephrine-dopamine reuptake inhibition 1
• This pharmacokinetic and pharmacodynamic synergy likely accounts for the rapid onset of action 6

Patient Selection Considerations

Discuss adverse effect profiles, cost, insurance coverage, and patient preferences when selecting Auvelity, as second-generation antidepressants show similar overall efficacy. 4, 7

Key Discussion Points

• Expected timeline for therapeutic effects (2 weeks vs. 4-6 weeks for traditional antidepressants) 4, 1
• Adverse effect profile (generally mild-to-moderate and well-tolerated) 4, 1
• Cost and accessibility, including insurance coverage and out-of-pocket expenses 4
• Prior medication experiences and treatment failures 4

Common Pitfalls

• Do not assume all patients require 6-8 weeks before assessing response; Auvelity demonstrates efficacy within 2 weeks 1
• Avoid premature discontinuation—while early response occurs, continuation treatment for 4-9 months is necessary to prevent relapse 4
• Consider that 71.2% of real-world patients use Auvelity as add-on therapy rather than switching from their current antidepressant 3

Safety and Tolerability

• Most common adverse events are mild-to-moderate in severity 1
• The combination is well-tolerated with sustained use through 12-15 months 1
• Bupropion component provides lower rates of sexual dysfunction compared to SSRIs like fluoxetine, sertraline, and paroxetine 8