What is the recommended treatment plan for major depressive disorder using Auvelity (dextromethorphan-bupropion)?

Auvelity (Dextromethorphan-Bupropion) Treatment Plan for Major Depressive Disorder

Recommended Treatment Approach

Auvelity should be initiated with a structured 4-week titration schedule, starting with one tablet daily in the morning and escalating weekly until reaching the maintenance dose of two tablets twice daily, with treatment response expected within 1-2 weeks. 1, 2

Dosing and Titration Protocol

Standard Titration Schedule

• Week 1: 1 tablet once daily in the morning 3
• Week 2: 1 tablet twice daily 3
• Week 3: 2 tablets in the morning and 1 tablet in the afternoon 3
• Week 4 onward: 2 tablets twice daily (maintenance dose) 3

Critical Timing Considerations

• The second daily dose must not be taken late in the day to minimize insomnia risk 3
• Significant reductions in Montgomery-Åsberg Depression Rating Scale (MADRS) scores occur as early as 1 week post-treatment (LS mean difference 2.2; 95% CI 0.6-3.9; p = 0.007) 2
• By week 2, MADRS score improvements are substantial compared to active controls (LS mean difference 4.7; 95% CI 0.6-8.8; p = 0.024) 2

Dose Adjustments for Special Populations

Renal Impairment

• Moderate to severe renal impairment: Reduce total daily dose by one-half (1 tablet twice daily) 3
• End-stage renal disease: Avoid use entirely 3

Hepatic Impairment

• Moderate to severe hepatic impairment: Maximum dose of 1 tablet daily 3

Treatment Response Assessment

Early Monitoring

• Assess patient status, therapeutic response, and adverse effects within 1-2 weeks of initiation 3
• Continue regular monitoring throughout the acute phase 3

Decision Point at 12 Weeks

• If the patient has not lost 5% of total body weight after 12 weeks on maintenance dose, discontinue the medication as they are likely a poor responder 3
• Note: This criterion is from obesity treatment guidelines but reflects the general principle of assessing adequate response

Modification Timeline for Depression

• Modify treatment if inadequate response within 6-8 weeks of initiation 3, 4

Expected Outcomes

Short-Term Efficacy

• Remission and response rates are significantly higher with dextromethorphan-bupropion compared to placebo in phase 3 trials 1
• Response rates exceed 80% in long-term studies 1

Long-Term Maintenance

• Treatment efficacy can be maintained for up to 12-15 months with mean MADRS score reductions of 23 points from baseline 1, 2
• Remission rates approach 70% in long-term open-label studies 1
• Continue treatment for 4-9 months after satisfactory response for first episode of MDD 3, 4
• For patients with 2 or more depressive episodes, longer duration of therapy is beneficial 3, 4

Clinical Use Patterns

Treatment Line Positioning

• Can be used as first-line therapy in treatment-naïve patients (10.1% of real-world users) 5
• Effective as second-line option after failure of serotonin-targeting agents 6
• Applicable for treatment-resistant depression 6

Monotherapy vs. Add-On

• 28.8% of patients initiate Auvelity as monotherapy 5
• 71.2% use it as add-on therapy, most frequently combined with SSRIs (10.7%) or SNRIs (6.5%) 5

Absolute Contraindications

Opioid Therapy Conflicts

• Do not use in patients requiring short-term or long-term opiate therapy, as the naltrexone component in similar formulations could reduce analgesic efficacy or precipitate withdrawal 3
• Discontinue before procedures requiring opiates (e.g., fentanyl during endoscopies) 3

Seizure Risk

• Avoid in patients with epilepsy 3
• Use with extreme caution in patients with history of seizures or clinical factors that increase seizure risk, as bupropion lowers the seizure threshold 3

Drug Interactions

• Avoid in patients treated with monoamine oxidase inhibitors or within 14 days of discontinuing MAOIs 3

Cardiovascular Concerns

• Avoid in patients with uncontrolled hypertension 3
• Monitor vital signs regularly in all treated patients 3

Safety Monitoring

Neuropsychiatric Surveillance

• Observe for neuropsychiatric adverse effects, including suicidal thoughts and behaviors, especially in individuals younger than 24 years 3
• Counsel patients and families about these risks 3

Common Adverse Events

• Most adverse events are rated as mild-to-moderate and transient 1, 2
• The medication is well-tolerated in clinical trials 1

Mechanism of Action Advantages

• Dextromethorphan modulates glutamate signaling through uncompetitive NMDA receptor antagonism and sigma-1 receptor agonism 1
• Bupropion increases dextromethorphan bioavailability via CYP2D6 inhibition 1
• This combination provides a mechanistically distinct approach from traditional monoamine-based antidepressants 2
• Bupropion offers minimal sexual dysfunction compared to SSRIs like fluoxetine and sertraline 4