Main Research Findings

Dextromethorphan-bupropion (Auvelity) is a combination medication approved by the Food and Drug Administration (FDA) for the treatment of major depressive disorder in adults. 1 . This medication combines dextromethorphan, which modulates glutamate signaling by antagonizing N-methyl-D-aspartate (NMDA) receptors and acting as a sigma-1 receptor agonist, and bupropion, which enhances dextromethorphan's bioavailability by inhibiting CYP2D6. 1 . In a phase 3 trial, patients with major depressive disorder who received dextromethorphan-bupropion (45-105 mg) experienced a significant reduction in their Montgomery-Åsberg Depression Rating Scale (MADRS) total scores compared to placebo. 1 . A phase 2 trial comparing dextromethorphan-bupropion (45-105 mg) to bupropion monotherapy also demonstrated a significant reduction in MADRS scores. 1 . Both clinical trials observed changes in MADRS scores within two weeks of starting dextromethorphan-bupropion treatment. 1 . The medication was well-tolerated in both trials, with most adverse events being mild-to-moderate in severity. 1 . Long-term open-label studies using dextromethorphan-bupropion revealed substantial reductions in MADRS scores that persisted for 12 and 15 months of treatment. 1 . Remission rates approached 70% in both long-term studies, while response rates exceeded 80%. 1 . These data suggest that dextromethorphan-bupropion is an effective, fast-acting, and well-tolerated option for depression treatment, leading to remission in a significant proportion of patients. 1 .

Benefits and Risks

Benefits Summary

Dextromethorphan-bupropion has shown potential as a treatment for major depressive disorder. 1 . Clinical trials have demonstrated that it effectively reduces depressive symptoms compared to placebo, with a rapid onset of action and good tolerability. 1 . Long-term open-label studies also show high remission and response rates, with sustained improvement in depressive symptoms. 1 .

Risks Summary

Like all antidepressants, dextromethorphan-bupropion carries a boxed warning regarding the potential for increased risk of suicidal thoughts and behaviors in pediatric and young adult patients. 4 . Seizures can occur, and the risk is higher at higher doses. 4 . Common adverse effects include dizziness, nausea, headache, diarrhea, drowsiness, dry mouth, sexual dysfunction, hyperhidrosis, anxiety, constipation, decreased appetite, and insomnia. 4 .

Comparison of Studies

Similarities in Studies

Multiple studies suggest that dextromethorphan-bupropion is a potentially effective treatment for major depressive disorder. 1 7 8 . These studies consistently show that it is more effective at reducing depressive symptoms compared to placebo or other antidepressants. 1 7 . Furthermore, these studies highlight that dextromethorphan-bupropion generally has good tolerability. 1 7 .

Differences in Studies

Slight variations exist in the effectiveness and side effect profiles of dextromethorphan-bupropion across different studies. 1 7 8 . These differences could be attributed to factors such as study design, participant characteristics, dosage, and other variables. 1 7 8 .

Consistency and Inconsistencies in Findings

While research consistently points towards dextromethorphan-bupropion's potential efficacy in treating major depressive disorder, there is some variability in the extent of effectiveness and side effect profiles. 1 7 8 . Furthermore, research on its long-term safety and effectiveness is limited. 1 7 8 .

Considerations for Real-World Application

Although dextromethorphan-bupropion is FDA-approved for major depressive disorder, it is not a cure-all and may not be effective for all patients. 1 . It's essential to take the medication as prescribed by a physician, as it carries the risk of adverse effects. 4 . Special caution is needed in children and adolescents due to the heightened risk of suicidal thoughts and behaviors. 4 . It is crucial to consult with a healthcare professional before starting this medication to carefully weigh its potential benefits and risks. 1 4 .

Limitations of Current Research

Research on dextromethorphan-bupropion is still relatively limited. 1 7 8 . Data on its long-term safety and effectiveness are particularly lacking. 1 7 8 . Furthermore, research comparing dextromethorphan-bupropion to other antidepressants is also insufficient. 1 7 8 .

Future Research Directions

Further research is needed to evaluate the long-term safety and effectiveness of dextromethorphan-bupropion. 1 7 8 . Comparisons to other antidepressants are also crucial. 1 7 8 . Research should also identify the patient groups who might benefit most from this medication. 1 7 8 .

Conclusion

Dextromethorphan-bupropion has shown promise as a potential treatment for major depressive disorder, with indications of effectiveness, rapid action, and good tolerability. 1 7 8 . However, research on its long-term safety and effectiveness is limited, and further studies are warranted. 1 7 8 . If you are considering using this medication, it is essential to consult with your physician to carefully weigh the potential benefits and risks. 1 4 .