From the Guidelines
Auvelity is a prescription medication used to treat major depressive disorder (MDD) in adults, containing two active ingredients: dextromethorphan hydrobromide and bupropion hydrochloride. Auvelity works differently from many other antidepressants as it targets the NMDA receptor system in the brain, with dextromethorphan acting as an NMDA receptor antagonist while bupropion inhibits the reuptake of dopamine and norepinephrine and also prevents the breakdown of dextromethorphan. The standard dosage is one tablet twice daily, taken at least 8 hours apart, with or without food. Patients typically start with one tablet once daily for the first three days, then increase to the standard dose. Auvelity may provide faster relief of depressive symptoms compared to traditional antidepressants, sometimes within 1-2 weeks rather than the typical 4-6 weeks. Common side effects include dizziness, headache, diarrhea, dry mouth, and excessive sweating. Patients should avoid alcohol while taking Auvelity and should inform their doctor about all other medications they're taking to avoid potential interactions, particularly with MAO inhibitors which can cause dangerous reactions 1. Key considerations for treatment include discussing adverse event profiles with patients before selecting a medication, as differences have been reported among some medications in mild to major adverse effects, such as sexual dysfunction and suicidality 1. It is essential to monitor patients closely for increases in suicidal thoughts and behaviors, especially during the first 1 to 2 months of treatment 1. Regular assessment of patient status, therapeutic response, and adverse effects of antidepressant therapy is crucial, beginning within 1 to 2 weeks of initiation of therapy 1. Treatment modification may be necessary if the patient does not have an adequate response to pharmacotherapy within 6 to 8 weeks of the initiation of therapy for major depressive disorder 1. Cognitive behavioral therapy (CBT) is a reasonable approach for initial treatment and should be strongly considered as an alternative treatment to second-generation antidepressants (SGAs) where available, given its probable fewer adverse effects and lower relapse rates compared to SGAs 1.
From the Research
What is Auvelity
- Auvelity is a novel, oral N-methyl-D-aspartate (NMDA) receptor antagonist and sigma-1 receptor agonist approved by the FDA for treating major depressive disorder (MDD) in adults 2.
- It is a combination of dextromethorphan and bupropion, and is available as an extended-release fixed combination 3.
- Auvelity has demonstrated efficacy in adults with MDD, with a relatively rapid onset of action 4, 5.
- The combination of dextromethorphan and bupropion represents a pharmacokinetic and pharmacodynamic synergy, which may account for the rapidity of action in MDD 5.
Mechanism of Action
- Auvelity works by targeting glutamatergic signaling, which is a potential therapeutic target in MDD 6, 5.
- Dextromethorphan, a component of Auvelity, has been shown to exhibit clinically significant antidepressant effects in preclinical and clinical studies 5.
Safety and Tolerability
- Auvelity carries a boxed warning that it may increase the risk of suicidal thoughts and behaviors in pediatric and young adult patients 3.
- Common adverse effects of Auvelity include dizziness, nausea, headache, diarrhea, somnolence, dry mouth, sexual dysfunction, hyperhidrosis, anxiety, constipation, decreased appetite, and insomnia 3.
- Seizures can also occur with Auvelity, and are more likely at higher doses 3.
Clinical Use
- Auvelity can be used as a first-line therapy, as a second option when a patient has failed to achieve remission with a serotonin-targeting agent, and for treatment-resistant depression 4.
- Further research is needed to determine the efficacy of Auvelity in other indications, such as addiction disorders 4.