The novel combination drug dextromethorphan-bupropion (Auvelity) was recently approved by the FDA as an oral antidepressant that works rapidly to treat major depressive disorder in adults.
This new medication represents an exciting development for depression treatment. Here are some key facts about this drug:
- Works significantly faster than standard antidepressants, showing efficacy in as little as 1 week.
- Achieves high rates of remission (39.5%) and response (54%) in 6 weeks.
- Oral tablet taken twice daily, avoiding restrictions of IV or nasal drugs.
- Appears well-tolerated compared to other fast-acting agents like ketamine.
How Does Dextromethorphan-Bupropion (Auvelity) Work?
Dextromethorphan is combined with bupropion in one tablet to create a novel mechanism of action for depression.
Dextromethorphan acts as an NMDA receptor antagonist and sigma-1 receptor agonist, while bupropion blocks reuptake of dopamine and norepinephrine.
Together, they modulate glutamate and enhance neuroplasticity.
Bupropion also inhibits the enzyme CYP2D6 which normally metabolizes dextromethorphan rapidly.
This increases dextromethorphan’s half-life to 22 hours, allowing sustained activity with twice daily dosing.
Dextromethorphan-Bupropion: Efficacy Demonstrated in Clinical Trials
Three published randomized controlled trials have demonstrated dextromethorphan-bupropion’s efficacy for major depression.
A phase 2 study in 80 adults found significantly greater improvement in Montgomery-Åsberg Depression Rating Scale (MADRS) scores after 6 weeks compared to bupropion alone.
Remission rates were 46.5% with dextromethorphan-bupropion versus only 16.2% with bupropion.
A larger phase 3 trial in 327 patients also showed dextromethorphan-bupropion superior to placebo in reducing MADRS scores over 6 weeks.
Remission was achieved by 39.5% on active drug versus 17.3% on placebo.
Importantly, these trials revealed a rapid onset of antidepressant effect within 1-2 weeks.
This is unlike standard antidepressants that typically take 4-8 weeks to work.
Dextromethorphan-Bupropion: Side Effects (Common)
Overall, dextromethorphan-bupropion appears well-tolerated based on clinical trials.
The most common side effects were dizziness, nausea, headache and dry mouth – mostly mild to moderate in severity.
There was no evidence of concerning adverse events seen with similar fast-acting drugs like ketamine and esketamine, such as dissociation, psychosis, sedation or abuse potential.
However, the combination product does still carry a seizure risk due to the bupropion component.
Long-Term Use Looks Promising
In open-label extension studies where patients took dextromethorphan-bupropion for up to 15 months, high response and remission rates were maintained over time.
After 12 months, response rates exceeded 80% while remission rates approached 70%.
This data on long-term treatment with dextromethorphan-bupropion is encouraging.
It suggests the drug provides durable relief of depression when taken continuously.
Unanswered Questions Remain
While dextromethorphan-bupropion shows considerable promise as a novel oral antidepressant, there are still unresolved issues to address.
Its efficacy in treatment resistant depression was not clearly established in an unpublished trial.
It also has not been studied in patients with substance abuse disorders, despite some risks of dextromethorphan misuse.
Additionally, the high cost of this patented combination product may limit its use compared to generic antidepressants.
More comparative effectiveness data is needed to determine where it fits amongst the many depression treatment options.
Overall Outlook on Dextromethorphan-Bupropion Combo for Depression
In conclusion, the new oral antidepressant dextromethorphan-bupropion appears to offer substantial benefits over existing therapies.
Its rapid onset of action, favorable side effect profile, and sustained efficacy make it an exciting potential first-line treatment for major depression.
While more research is still needed, this drug may provide new hope for faster relief to the millions suffering from this debilitating condition.
References
- Study: Dextromethorphan-bupropion for the treatment of major depressive disorder
- Authors: Brian McCarthy et al. (2023)
