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Auvelity vs. Wellbutrin: Effectiveness for Depression?

Medically reviewed by Carmen Pope, BPharm. Last updated on Sep 12, 2023.

Official answer

by drugclasses.com

Both Auvelity and Wellbutrin are effective for depression but a small RCT (n=80) reported that Auvelity worked significantly better than Wellbutrin and took less time to start working. 43 people prescribed Auvelity experienced an overall decrease in their Montgomery-Åsberg Depression Rating Scale (MADRS) score of 13.7 points after 6 weeks compared to a decrease of 8.8 points in the 37 people prescribed bupropion (least-squares mean difference=-4.9; 95% CI=-3.1, -6.8).

  • At week 2 and every time point thereafter, significantly larger changes in the MADRS score and remission rates were reported with Auvelity than bupropion (-12.5 vs. -7.8, least-squares mean difference=-4.7; 95% CI=-0.6, -8.8).
  • In addition, 60.5% of people taking Auvelity had at least a 50% decrease in their MADRAS score at week 6 compared with only 40.5% prescribed bupropion (least-squares mean difference=19.9%, 95% CI=-1.6, 41).
  • Most other outcomes favored Auvelity.
  • The most common side effects associated with Auvelity were dizziness, nausea, dry mouth, decreased appetite, and anxiety. It was not associated with psychotomimetic effects (hallucinations or delusions), weight gain, or sexual dysfunction.

Auvelity is a combination extended-release tablet containing dextromethorphan 45mg and bupropion 105mg, and Wellbutrin XL tablets contain 150mg of bupropion. The addition of dextromethorphan to Auvelity means that it also has a direct effect on the N-methyl-D-aspartate (NMDA) receptor because dextromethorphan is an NMDA receptor antagonist. NMDA receptors are located on nerve cells, mostly at excitatory synapses, and research has shown that they can become overstimulated when glutamate levels are high. Previous studies have shown that NMDA receptor antagonists can have antidepressant effects. In Auvelity, the bupropion component has a similar antidepressant effect to that experienced by people taking Wellbutrin, but , it also boosts concentrations of dextromethorphan in the blood by competitively inhibiting cytochrome P450 2D6, an enzyme in the liver that breaks it down.

Auvelity is usually given twice a day after an initial titration period and Wellbutrin XL is usually given once a day.

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References
  • Wellbutrin Product Information. https://www.accessdata.fda.gov/drugsatfda_docs/label/2011/018644s043lbl.pdf
  • Auvelity Product Information. https://www.axsome.com/auvelity-prescribing-information.pdf
  • Tabuteau, H., Jones, A., Anderson, A., Jacobson, M., & Iosifescu, D. V. (2022). Effect of AXS-05 (Dextromethorphan-Bupropion) in Major Depressive Disorder: A Randomized Double-Blind Controlled Trial. The American journal of psychiatry, 179(7), 490–499. https://doi.org/10.1176/appi.ajp.21080800

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