Exploring the Active Ingredients of Auvelity
Auvelity is an oral medication that combines two active ingredients in an extended-release formulation. These are dextromethorphan hydrobromide and bupropion hydrochloride. The combination of these two drugs provides a new approach for treating depression.
The Role of Dextromethorphan
Dextromethorphan is central to Auvelity's antidepressant effects. It is an NMDA (N-methyl-D-aspartate) receptor antagonist and a sigma-1 receptor agonist. These actions affect the neurotransmitter glutamate. The NMDA antagonism provides an effect similar to ketamine. However, dextromethorphan is quickly metabolized, which limits its therapeutic potential on its own.
The Role of Bupropion
Bupropion plays two key roles in the Auvelity formulation. First, it works as a norepinephrine and dopamine reuptake inhibitor (NDRI). Second, it inhibits the CYP2D6 enzyme. This inhibition slows down the metabolism of dextromethorphan. This increases and prolongs its availability, which allows the NMDA-antagonist action to be sustained.
Comparing Auvelity with Other Antidepressants
Auvelity has a different mechanism of action than many traditional antidepressants like SSRIs and SNRIs.
| Feature | Auvelity (dextromethorphan/bupropion) | Traditional Antidepressants (SSRIs/SNRIs) | Bupropion (Wellbutrin) | Spravato (esketamine) |
|---|---|---|---|---|
| Primary Mechanism | NMDA antagonist (dextromethorphan) + NDRI (bupropion) | Modulates monoamines (serotonin, norepinephrine) | NDRI only | NMDA antagonist |
| Onset of Action | As early as 1 week | Typically 4 to 8 weeks | Slower than Auvelity | 2 to 4 hours (administered by a professional) |
| Administration | Oral extended-release tablet | Oral tablets/capsules | Oral tablets/capsules | Clinician-administered nasal spray |
| Efficacy | Superior to bupropion alone in clinical trials | Can be effective but slower onset | Effective, but less so than Auvelity in head-to-head trials | Treatment-resistant depression |
| Sexual Side Effects | Significantly lower incidence than SSRIs/SNRIs | Common for many patients | Lower incidence | Not directly compared |
Side Effects and Warnings Associated with Auvelity
Auvelity has side effects and warnings that patients should discuss with their doctors.
- Boxed Warning for Suicidality: Like other antidepressants, Auvelity has a boxed warning for increased risk of suicidal thoughts and behaviors in young adults, adolescents, and children. Auvelity is only approved for adults.
- Seizure Risk: Bupropion can lower the seizure threshold. Auvelity is not for patients with a history of seizure disorders, eating disorders, or those undergoing alcohol or sedative withdrawal.
- Increased Blood Pressure: Bupropion may cause elevated blood pressure. Regular blood pressure monitoring is recommended.
- Common Side Effects: Common side effects in clinical trials included dizziness, nausea, dry mouth, and headache.
- Serotonin Syndrome: Combining Auvelity with other serotonergic drugs can increase the risk of serotonin syndrome.
- Mania Activation: Patients with bipolar disorder or a history of mania are at risk for manic episodes.
Clinical Trial Data
The FDA approval of Auvelity was based on data from the GEMINI and ASCEND clinical trials.
- GEMINI Trial: This study showed that Auvelity significantly improved depression symptoms compared to a placebo. Improvement was observed as early as one week.
- ASCEND Trial: This study compared Auvelity to bupropion alone. Auvelity was more effective at reducing depression symptoms and achieving remission than bupropion alone.
Conclusion
Auvelity combines dextromethorphan and bupropion to treat major depressive disorder (MDD) in adults. The combination modulates the brain's glutamatergic system via dextromethorphan, while bupropion extends the duration of action. Clinical trials have shown its efficacy, particularly its rapid onset compared to traditional oral antidepressants and its superiority to bupropion alone. Patients considering this treatment should have a thorough discussion with their healthcare provider about the benefits, side effects, and important safety considerations, particularly concerning seizure risk and the boxed warning for suicidality. The official AUVELITY website for healthcare professionals provides additional information.
