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: Do not exceed 1 tablet daily total 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 weight loss criterion is from obesity treatment guidelines; for MDD, assess depression severity using validated scales 3

Inadequate Response Protocol

• Modify treatment if inadequate response occurs within 6-8 weeks of initiation 3, 4
• Switching to another second-generation antidepressant after failed bupropion trial results in 25% achieving remission 4

Duration of Treatment

First Episode MDD

• Continue treatment for 4-9 months after satisfactory response 3, 4

Recurrent Depression

• Longer duration of therapy is beneficial for patients with 2 or more episodes 3, 4

Long-Term Efficacy

• Treatment efficacy can be maintained for up to 12-15 months with mean MADRS score reductions of 23 points from baseline 2
• Remission rates approach 70% and response rates exceed 80% in long-term studies 1

Absolute Contraindications

Opioid Therapy Conflicts

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

Cardiovascular Precautions

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

Drug Interactions

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

Clinical Positioning

First-Line Use

• Auvelity can be initiated as first-line monotherapy for MDD in adults 5, 6
• Real-world data shows 10.1% of patients initiated Auvelity without prior treatment in the preceding 12 months 6

Second-Line Use

• Appropriate when patients fail to achieve remission with serotonin-targeting agents (SSRIs/SNRIs) 5
• In real-world practice, 83.7% of patients had received prior treatment with SSRIs (54.9%), bupropion (40.4%), or SNRIs (35.9%) 6

Add-On Therapy

• Can be added to existing antidepressant therapy 6
• Real-world data shows 71.2% of patients initiated Auvelity as add-on therapy, most frequently with SSRIs (10.7%) or SNRIs (6.5%) 6

Adverse Event Profile

Common Adverse Events

• Most adverse events are rated as mild-to-moderate in severity 1
• The medication is well-tolerated in clinical trials 1, 2
• Transient adverse events may occur but typically resolve 2

Sexual Dysfunction Advantage

• Bupropion component offers significantly lower rates of sexual dysfunction compared to SSRIs like fluoxetine and sertraline 3, 4

Neuropsychiatric Monitoring

• 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

Mechanism of Action

• Dextromethorphan modulates glutamate signaling through uncompetitive N-methyl-D-aspartate (NMDA) receptor antagonism and sigma-1 receptor agonism 1, 7
• Bupropion increases dextromethorphan bioavailability by inhibiting CYP2D6 1, 7
• This combination supports the mechanistic role of glutamatergic and sigma-1 signaling in MDD pathophysiology 2