There have been no head-to-head trials comparing Auvelity to Wellbutrin with regards to effectiveness for depression, but Auvelity probably has a quicker onset of action than Wellbutrin, with some people experiencing symptom relief in as little as one week. Traditional antidepressants, such as Wellbutrin, usually take 4 to 6 weeks to work, although some improvement in symptoms such as sleep, energy, and appetite may be noticed in the first week or two.

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.