Auvelity worked significantly better than Wellbutrin (bupropion) at relieving symptoms of depression in a small randomized double-blind, parallel trial that lasted for 6 weeks. It also had a faster onset of effect, with improvement in the Montgomery-Åsberg Depression Rating Scale (MADRS) score being observed as early as week 1 and differences being statistically significant by week 2.

• 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).
• The change in the MADRS score and remission rates with Auvelity were also significantly greater than with bupropion at week 2 and every time point thereafter (-12.5 vs. -7.8, least-squares mean difference=-4.7; 95% CI=-0.6, -8.8).
• 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 in addition, it 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.