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 they can be taken with or without food. The full antidepressant effect may take several weeks to develop, so patients should continue treatment even if benefits aren't immediately apparent. 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, eating disorders, or those undergoing abrupt discontinuation of alcohol, benzodiazepines, or antiepileptic drugs. It's also contraindicated with MAOIs, requiring at least 14 days between stopping an MAOI and starting Auvelity. The medication works through NMDA receptor antagonism and modulation of monoamine neurotransmitters, providing a novel mechanism for treating depression compared to traditional antidepressants. Key considerations in treating major depressive disorder include assessing 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. Monitoring for increases in suicidal thoughts and behaviors should begin 1 to 2 weeks after initiation of therapy, with a higher risk for suicide attempts during the first 1 to 2 months of treatment 1. Treatment should be modified 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. The American College of Physicians recommends that clinicians select second-generation antidepressants on the basis of adverse effect profiles, cost, and patient preferences 1. Bupropion is associated with a lower rate of sexual adverse events than fluoxetine or sertraline, whereas paroxetine has higher rates of sexual dysfunction than fluoxetine, fluvoxamine, nefazodone, or sertraline 1. SSRIs are associated with an increased risk for suicide attempts compared with placebo 1. Physicians and patients should discuss adverse event profiles before selecting a medication 1. The response rate to drug therapy may be as low as 50%, and multiple pharmacologic therapies might be required for patients who do not respond to first- or second-line treatments 1. Insufficient evidence exists to prefer one agent over another as second-line therapy 1. The American College of Physicians recommends that clinicians continue treatment for 4 to 9 months after a satisfactory response in patients with a first episode of major depressive disorder, and for patients who have had 2 or more episodes of depression, an even longer duration of therapy may be beneficial 1. Depressive disorders are serious disabling illnesses that affect 16% of adults in the United States during their lifetime, with an estimated economic burden of $83.1 billion 1. The course of depression can be characterized by 3 phases, and relapse is defined as the return of depressive symptoms during the acute or continuation phases, whereas recurrence is defined as the return of depressive symptoms after a period of recovery 1. The American College of Physicians clinical practice guidelines grading system is used to grade the evidence and recommendations 1. Key points to consider when treating major depressive disorder with Auvelity include the potential for adverse effects, the importance of monitoring patient status and therapeutic response, and the need to modify treatment if the patient does not have an adequate response to pharmacotherapy 1. The medication should be used with caution in patients with certain medical conditions, such as seizure disorders, eating disorders, or those undergoing abrupt discontinuation of alcohol, benzodiazepines, or antiepileptic drugs 1. In addition, Auvelity should not be used in patients taking MAOIs, and at least 14 days should be allowed between stopping an MAOI and starting Auvelity 1. Overall, the treatment protocol for Auvelity in adults with major depressive disorder should be individualized based on the patient's specific needs and medical history, and should be guided by the principles of evidence-based medicine and the recommendations of the American College of Physicians 1.

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
• The combination of dextromethorphan and bupropion 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
• 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

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

Patient Characteristics

• Adult patients initiating Auvelity had a mean age of 45.1 years, with 68.1% being women 5
• Comorbidities included mental health disorders, with 53.5% having anxiety disorders 5
• Prior MDD-related medications included selective serotonin reuptake inhibitors (SSRIs), norepinephrine-dopamine reuptake inhibitors (NDRIs), and serotonin-norepinephrine reuptake inhibitors (SNRIs) 5

Safety and Efficacy

• The medication was well-tolerated in both trials, with the most common adverse events being rated as mild-to-moderate 4
• Two long-term, open-label studies with dextromethorphan-bupropion saw large reductions in Montgomery-Åsberg Depression Rating Scale scores that were maintained through 12 and 15 months of treatment 4
• Remission rates approached 70%, while response rates were greater than 80% in both long-term studies 4