Auvelity may start to lessen your symptoms of depression after one week of treatment. The percentage of patients who achieved symptoms that were “very much improved / much improved” at one week were 22% for Auvelity vs. 13% for placebo, a significant effect. In studies, over 50% of patients achieved a clinical response by the 6th week of treatment.

• Auvelity is an antidepressant that works differently, and it is the only oral medication with significant improvement in depressive symptoms (compared to placebo) starting at Week 1.
• This is important because many common antidepressants, like the selective serotonin reuptake inhibitors (SSRIs), can take several weeks or longer to have a noticeable effect on depressive symptoms.
• Common SSRIs you may be familiar with include fluoxetine (Prozac), sertraline (Zoloft), or escitalopram (Lexapro).

When was Auvelity approved?

In August 2022 the FDA approved Auvelity (dextromethorphan and bupropion) extended-release tablets for the treatment of major depressive disorder (MDD) in adults.

Auvelity, from Axsome Therapeutics, is the first oral N-methyl-D-aspartate (NMDA) receptor antagonist approved for the treatment of MDD, and provides the first new oral mechanism of action for depression in more than 60 years.

Overview

Auvelity has been shown to exhibit a significant and sustained antidepressant effect starting at Week 1 after treatment is started when compared to a placebo.

• In the Phase 3 GEMINI study the primary endpoint of symptom improvement on the Montgomery–Asberg Depression Rating Scale (MADRS) total score from baseline to Week 6 was met (MADRS point reduction: -15.9 Auvelity vs. -12.1 placebo, p=0.002). MADRS is a clinician-rated measure of depression severity.
• In addition, the change in MADRS at Week 1 and Week 2 (a secondary endpoint), was met.
• In this study, the percentage of patients taking Auvelity who had symptoms that were “very much improved / much improved” by Week 1 was 22% vs. 13% placebo, a significant effect (p=0.035).
• Patients also reached remission from depression symptoms by Week 2 ((MADRS score less than or equal to 10).

By Week 2, a greater number of patients had reached remission (MADRS score less than or equal to 10) or a clinical response (defined as 50% improvement in MADRS total score from the start of the study) and this number increased over 6 weeks, when compared to placebo.

GEMINI Study

The GEMINI study was a Phase 3, double-blind, placebo-controlled study in 327 patients with major depressive disorder (MDD) that evaluated Auveity compared to a placebo for a total of 6 weeks. Patients were randomized to receive Auvelity (45 mg of dextromethorphan hydrobromide and 105 mg of bupropion hydrochloride) twice daily or placebo twice daily.

The primary endpoint was symptom improvement on the MADRS total score at Week 6. Key secondary endpoints were change in MADRS total score from baseline to Week 1 and Week 2, clinical response at Week 6, and remission at Week 2. Scores on the MADRS range from 0 to 60, with higher scores indicating more severe depression.

Auvelity was shown to reach a rapid and statistically significant antidepressant effect starting one week after treatment was started compared to an inactive placebo. This effect was sustained throughout 6 weeks.

• In the Phase 3 GEMINI double-blind, placebo-controlled study of 327 patients with major depressive disorder (MDD), the primary endpoint of symptom improvement on the MADRS total score from baseline to Week 6 was met (MADRS point reduction: -15.9 Auvelity vs. -12.1 placebo, p=0.002)
• Auvelity exhibited a statistically significant and sustained antidepressant effect starting at week 1 compared to a placebo (MADRS point reduction: -7.2 Auvelity vs. -5.0 placebo, p=0.007), and at Week 2 (MADRS point reduction: -11.1 Auvelity vs. -7.7 placebo, p <0.001), a secondary effect.
• The minimal clinically important difference (MCID) for MADRS is a 2 point difference between treatment groups.

Symptom Improvement (CGI-I)

Table 1. In GEMINI, the percentage of patients who achieved symptoms that were “very much improved / much improved” (CGI-I = Clinical Global Impression-Improvement Score)

_{^{*difference from placebo was statistically significant; P-values for Weeks 2-4 were not calculated.}}

Remission

More patients taking Auvelity achieved remission (defined as a MADRS total score ≤10) at Week 2, with the number of patients increasing up to Week 6.

• Week 2: 17% Auvelity vs. 8% placebo (p=0.013)
• Week 6: 40% Auvelity vs. 17% placebo

Clinical Response

Table 2. More patients taking Auvelity achieved a significant clinical response (defined as 50% improvement in MADRS total score from the start of the study) by Week 6.

_{*difference statistically significant; P-values for Weeks 1-4 were not calculated.}

What is the mechanism of action of Auvelity?

Auvelity (dextromethorphan and bupropion) is thought to work by modulating glutamatergic neurotransmission in your brain. Each extended-release tablet contains dextromethorphan hydrobromide 45 mg and bupropion hydrochloride 105 mg, two medicines that may contribute to its effectiveness in depression.

• Dextromethorphan is an antagonist at the N-methyl-D-aspartate (NMDA) receptors (which means it blocks these receptors), but is also an agonist at the sigma-1 receptors (stimulates these receptors). This dual activity makes glutamate more available in your brain and helps to have a positive effect on your mood to ease depressive symptoms.
• Bupropion is an aminoketone and CYP2D6 inhibitor. It blocks an enzyme that metabolizes (breaks down) dextromethorphan which increases and prolong the blood levels of dextromethorphan. Bupropion may also weakly affect neurotransmitters (chemical transmitters) like norepinephrine and dopamine in your brain.

How do I take Auvelity?

• The initial recommended dose is one tablet once daily in the morning, which is increased to one tablet twice daily after 3 days. Do not take more than two doses within the same day.
• Swallow the tablets whole: do not chew, divide or crush the tablets.
• You can take Auvelity with or without food.

Your doctor may need to adjust your dose if you have kidney impairment or changes in the way you metabolize (break down) the medicine in your body.

Take Auvelity exactly as your doctor prescribes it.

What are the common side effects with Auvelity?

Common side effects (in at least 5% of patients) include:

• dizziness
• headache
• diarrhea
• somnolence (drowsiness)
• dry mouth
• sexual dysfunction
• hyperhidrosis (excessive sweating)

Auvelity also carries a Boxed Warning for suicidal thoughts and behaviors. Other warnings and precautions include: increased seizure risk, increased blood pressure / hypertension, mania or hypomania, psychosis and other neuropsychiatric reactions, angle-closure glaucoma, dizziness, serotonin syndrome, and embryo-fetal toxicity.

This is not all the information you need to know about Auvelity for safe and effective use and does not take the place of your doctor’s directions. Review the full product information and discuss this information and any questions you have with your doctor or other health care provider.