Auvelity contains two active ingredients: 45 mg of dextromethorphan hydrobromide and 105 mg of bupropion hydrochloride. It’s a prescription medication approved by the FDA in 2022 to treat major depressive disorder in adults, and more recently approved to treat agitation associated with Alzheimer’s-related dementia. What makes it unusual is how the two ingredients work together: one is the therapeutic agent, and the other exists largely to keep the first one active in your body long enough to work.
The Two Active Ingredients
Dextromethorphan is the ingredient you might recognize from cough medicine. At the dose used in Auvelity, though, it serves a completely different purpose. It blocks a specific type of receptor in the brain involved in glutamate signaling, which is one of the brain’s primary chemical messaging systems. It also activates another receptor that may further influence both glutamate and the more traditional mood-regulating brain chemicals like serotonin, norepinephrine, and dopamine. This makes Auvelity the only antidepressant that works on both of these signaling systems simultaneously.
Bupropion, the second ingredient, plays a dual role. On its own, bupropion is already a well-known antidepressant (sold as Wellbutrin). But in Auvelity, its primary job is pharmacological: it blocks a liver enzyme that would otherwise break down dextromethorphan too quickly. Without bupropion in the mix, your body metabolizes dextromethorphan rapidly, and blood levels never stay high enough to produce an antidepressant effect. With bupropion blocking that enzyme, dextromethorphan’s half-life extends roughly threefold to about 22 hours, and steady-state blood levels climb dramatically, with accumulation ratios jumping from about 1.4 (dextromethorphan alone) to 32 (in the Auvelity combination).
Why This Combination Matters
Most traditional antidepressants work on a single system: serotonin, norepinephrine, or dopamine. Auvelity takes a different approach by also targeting glutamate, the brain’s most abundant excitatory chemical messenger. The theory is that modulating glutamate signaling through dextromethorphan’s receptor-blocking activity can produce antidepressant effects through a pathway that conventional medications don’t touch.
In the GEMINI clinical trial, people taking Auvelity saw their depression scores drop by 15.9 points over six weeks compared to 12.0 points for placebo. More practically, 54% of people on Auvelity achieved a clinical response (at least a 50% improvement in symptoms) compared to 34% on placebo. That 20-percentage-point gap is meaningful, and the medication has been described as faster-acting than many traditional antidepressants, partly because of this glutamate mechanism.
Inactive Ingredients
If you have allergies or sensitivities to specific compounds, the full list of inactive ingredients matters. Each Auvelity tablet contains: carbomer homopolymer, colloidal silicon dioxide, crospovidone, glyceryl monocaprylocaprate, L-cysteine hydrochloride monohydrate, magnesium stearate, microcrystalline cellulose, polyvinyl alcohol, red iron oxide, sodium lauryl sulfate, stearic acid, talc, titanium dioxide, and yellow iron oxide. The iron oxides are coloring agents, and most of the other ingredients serve as binders, fillers, or coatings that control how the tablet dissolves. The tablet itself is a multilayer design: dextromethorphan is in an immediate-release layer, while bupropion sits in an extended-release layer.
Key Drug Interactions
Because Auvelity contains both a serotonin-affecting ingredient and a dopamine-affecting ingredient, it has serious interactions with a specific class of medications called MAO inhibitors. These include older antidepressants and certain Parkinson’s disease drugs. Combining them with Auvelity can cause dangerous spikes in blood pressure or episodes of psychosis. At least 14 days must pass between stopping an MAO inhibitor and starting Auvelity.
The bupropion component also makes Auvelity a strong inhibitor of the same liver enzyme it uses to protect dextromethorphan. This means any other medication processed through that enzyme can build up to higher-than-expected levels in your body, potentially causing side effects. Your pharmacist or prescriber should review your full medication list before starting Auvelity to flag these interactions.
How Auvelity Is Taken
Auvelity comes as an extended-release tablet. The typical starting approach is one tablet daily for the first three days, then increasing to one tablet twice daily. The tablets should be swallowed whole, not crushed or split, since the layered design controls how each ingredient is released. Damaging that structure would release bupropion too quickly and undermine the controlled delivery the formulation depends on.