Auvelity for Major Depressive Disorder: Benefits and Pharmacy Considerations
Primary Benefits
Auvelity (dextromethorphan-bupropion) offers rapid antidepressant effects with significant symptom reduction within 2 weeks, achieving remission rates approaching 70% in long-term studies. 1
Efficacy Profile
Rapid onset of action: Significant reductions in Montgomery-Åsberg Depression Rating Scale (MADRS) scores occur within 2 weeks of treatment initiation, substantially faster than traditional second-generation antidepressants 1
Superior to bupropion monotherapy: Phase 2 trials demonstrated significantly greater MADRS score reductions compared to bupropion alone, indicating the dextromethorphan component provides meaningful additional benefit 1
High remission rates: Long-term open-label studies showed remission rates approaching 70% and response rates exceeding 80% maintained through 12-15 months of treatment 1
Sustained efficacy: Large reductions in depression severity scores were maintained throughout extended treatment periods 1
Mechanism of Action
Dual mechanism: Dextromethorphan modulates glutamate signaling through N-methyl-D-aspartate (NMDA) receptor antagonism and sigma-1 receptor agonism, while bupropion inhibits CYP2D6 to increase dextromethorphan bioavailability 1, 2
Novel approach: This represents a departure from traditional serotonin-targeting agents, offering an alternative mechanism for patients who have not responded to SSRIs or SNRIs 2
Clinical Use Patterns
Treatment Positioning
Versatile placement: Can be used as first-line therapy, as a second option after SSRI/SNRI failure, or for treatment-resistant depression 2
Real-world utilization: In clinical practice, 28.8% of patients initiate Auvelity as monotherapy while 71.2% use it as add-on therapy, most commonly added to SSRIs (10.7%) or SNRIs (6.5%) 3
Treatment-naïve patients: Approximately 10% of patients in real-world settings initiate Auvelity without prior antidepressant treatment in the preceding year 3
Prior treatment history: Most patients (83.7%) have previously tried SSRIs, bupropion (NDRI), or SNRIs before initiating Auvelity 3
Safety and Tolerability
Common Adverse Effects
The medication is generally well-tolerated with most adverse events rated as mild-to-moderate. 1
- Most frequent side effects: Dizziness, nausea, headache, diarrhea, somnolence, dry mouth, sexual dysfunction, hyperhidrosis, anxiety, constipation, decreased appetite, and insomnia 4
Critical Safety Warnings
Boxed warning for suicidality: Like all antidepressants, Auvelity carries a black box warning for increased risk of suicidal thoughts and behaviors in pediatric and young adult patients 4
Seizure risk: Seizures can occur and are more likely at higher doses; the medication is contraindicated in patients predisposed to seizures 4, 5
Dosage considerations: When bupropion dosage is maintained at 450 mg/day or less in divided schedules, seizure rates are comparable to other antidepressants in patients without increased seizure risk factors 5
Treatment Duration Guidelines
First Episode Depression
- Continue treatment for 4-9 months after achieving satisfactory response in patients with first episode major depressive disorder 6
Recurrent Depression
- Longer duration therapy is beneficial for patients who have experienced two or more depressive episodes 6
Monitoring Requirements
Regular assessment: Monitor patients on a regular basis beginning within 1-2 weeks of therapy initiation 7
Response evaluation: Modify treatment if patients do not show adequate response within 6-8 weeks of initiation 7
Pharmacy Dispensing Considerations
Patient Selection Factors
When selecting Auvelity, discuss the following with patients:
Treatment effects and expected timeline: Emphasize the rapid onset (within 2 weeks) compared to traditional antidepressants 1
Adverse effect profile: Review common side effects and seizure risk, particularly in patients with predisposing factors 4
Cost and accessibility: Consider insurance coverage and out-of-pocket costs, as this is a newer branded medication 6
Patient preferences: Incorporate patient values regarding treatment approach and prior medication experiences 6
Clinical Context
Comparable efficacy to other SGAs: While Auvelity offers rapid onset, second-generation antidepressants are generally equally effective for treating major depressive disorder when considering overall outcomes 6
Alternative to serotonin-targeting agents: Auvelity provides a mechanistically distinct option for patients who prefer or require alternatives to SSRIs/SNRIs 2
Familiarity advantage: Clinicians are already familiar with both component medications (dextromethorphan and bupropion), which may increase prescriber comfort and acceptability 2