Auvelity (Dextromethorphan/Bupropion)

Overview

Auvelity is a prescription oral medication combining dextromethorphan (45 mg) and bupropion (105 mg) that was approved by the FDA on August 18, 2022, for treating major depressive disorder (MDD) in adults¹. It represents a significant advancement in depression treatment as the first and only oral medication with a rapid onset of action, demonstrating statistically significant antidepressant efficacy starting at one week when compared to placebo¹. Dextromethorphan has historically been used as a cough suppressant, while bupropion is an established antidepressant; their combination creates a novel therapeutic approach that works through multiple mechanisms in the brain⁷.

Forms and Variations

Auvelity is available as an oral tablet taken by mouth². The medication comes in a fixed-dose combination containing 45 mg of dextromethorphan hydrobromide and 105 mg of bupropion hydrochloride per tablet⁴. Currently, there is one primary formulation available, though an extended-release version (Auvelity ER) has been referenced in clinical literature⁷. The fixed-dose combination approach ensures consistent dosing of both active ingredients, which is essential for the medication"s efficacy and safety profile. Unlike some antidepressants that come in multiple strength options, Auvelity"s single-strength formulation simplifies dosing protocols and reduces the risk of medication errors.

Dosage and Administration

The recommended starting dosage of Auvelity is one tablet taken once daily in the morning⁴. After 3 days of treatment, patients should increase to the maximum recommended dosage of one tablet twice daily, with doses taken at least 8 hours apart³⁴. The maximum daily dose is two tablets (210 mg bupropion and 90 mg dextromethorphan) within a 24-hour period³. Prior to initiating treatment, healthcare providers should assess blood pressure and screen for conditions that may contraindicate use⁴. If a dose is missed, patients should not take an extra dose to compensate; instead, they should wait and take their next scheduled dose⁶. It is essential to take Auvelity exactly as instructed by a healthcare provider.

Scientific Research and Mechanism of Action

Auvelity works through a unique multi-target mechanism that distinguishes it from other oral antidepressants³. The medication acts on N-methyl-D-aspartate (NMDA) receptors and sigma-1 receptors, making it the first and only oral treatment for MDD with this dual receptor action³. Dextromethorphan functions as an uncompetitive NMDA receptor antagonist and sigma-1 receptor agonist, while bupropion acts as an aminoketone that inhibits the reuptake of norepinephrine and dopamine⁴. Both components also act as alpha-4-beta-2 nicotinic (nACh) antagonists, further contributing to their antidepressant effects¹. The NMDA receptor is activated by glutamate, the brain"s primary excitatory neurotransmitter, and blocking this receptor may help reduce depressive symptoms³. The sigma-1 receptor is thought to help modulate brain chemistry and support neuroprotection³. Clinical trials involving more than 1,100 people with MDD demonstrated that Auvelity produced statistically significant improvements in depressive symptoms after 6 weeks compared to placebo, with patients maintaining an average of 11% greater reduction in depressive symptoms than placebo¹².

Benefits and Potential Uses

Auvelity is indicated specifically for the treatment of major depressive disorder in adults⁴. The primary benefit of Auvelity is its rapid onset of action; some patients experienced symptom relief as early as one week in clinical studies, with significant symptom relief observed on average at 6 weeks⁵. This rapid efficacy is particularly valuable given the debilitating nature of depression and the urgent need for symptom relief in affected individuals¹. The medication"s novel mechanism of action through NMDA and sigma-1 receptors, combined with its effects on dopamine and norepinephrine, provides a comprehensive approach to treating depressive symptoms³. According to psychiatrists and clinical experts, the approval of Auvelity represents a milestone in depression treatment based on its novel oral NMDA antagonist mechanism, rapid antidepressant efficacy demonstrated in controlled trials, and relatively favorable safety profile¹. The medication"s effectiveness may significantly alter the current paradigm for treating depression, offering hope to patients who need faster symptom relief.

Side Effects and Risks

Auvelity can cause increased blood pressure and hypertension, with increased risk when used with certain other medications⁴. The medication carries a black box warning regarding suicidal thoughts and behaviors; Auvelity and other antidepressant medicines may increase suicidal thoughts and actions in some children, adolescents, and young adults, especially within the first weeks of treatment⁶. Common side effects include dizziness, which may increase the risk of falls⁶. Serotonin syndrome, a potentially life-threatening condition, can occur when Auvelity is taken with certain other medications⁶. The medication also carries a risk of seizures, particularly in patients taking doses exceeding 400 mg per day of bupropion (approximately 2 times the maximum recommended daily dosage of Auvelity)⁴. Seizure risk is further related to patient factors, clinical situations, and concomitant medications that lower the seizure threshold⁴. In the 6-week placebo-controlled study, 4% of patients treated with Auvelity discontinued the medication due to adverse reactions, compared to 0% of placebo-treated patients⁴.

Interactions and Precautions

Auvelity is a CYP2D6 inhibitor, meaning it can increase the plasma concentrations of drugs metabolized by this enzyme, including risperidone, aripiprazole, codeine, metoprolol, and tamoxifen². The medication should not be used concurrently with certain classes of drugs, including selective serotonin reuptake inhibitors (SSRIs), tricyclic antidepressants, theophylline, corticosteroids, oral diabetes medicines, appetite suppressants, nicotine replacement therapies, and street drugs³⁶. Auvelity is contraindicated in patients with a history of seizures, eating disorders, or substance abuse⁵. Patients with bipolar disorder or a family history of bipolar disorder, suicide, or depression require careful evaluation before treatment⁵. The medication should be used with caution in patients with low blood sugar, low blood sodium levels, or a history of falls⁵. Auvelity is not approved for use in pediatric patients and should not be used during pregnancy or while breastfeeding³⁵. Patients with glaucoma or those who consume large amounts of alcohol or abuse prescription or street drugs should avoid this medication⁵.

Impact on Biomarkers

Auvelity affects multiple neurotransmitter systems and receptor pathways that influence various biological markers. The medication"s action on NMDA receptors and sigma-1 receptors, combined with its effects on dopamine and norepinephrine reuptake, influences brain chemistry markers related to mood regulation³. Blood pressure monitoring is recommended, as the medication can increase blood pressure and hypertension risk⁴. Additionally, patients taking Auvelity should be monitored for changes in blood glucose levels, as the medication may interact with oral diabetes medicines and insulin³. Sodium levels should also be monitored, particularly in patients with a history of low blood sodium⁵.

Overdose and Toxicity

While specific overdose data for Auvelity is limited in the provided literature, the bupropion component carries a risk of seizures at doses exceeding 400 mg per day, which is approximately 2 times the maximum recommended daily dosage of Auvelity⁴. Overdose risk is increased by patient factors, clinical situations, and concomitant medications that lower the seizure threshold⁴. The maximum recommended daily dose of Auvelity is two tablets (210 mg bupropion and 90 mg dextromethorphan) within a 24-hour period, and this limit should not be exceeded³. In case of overdose or suspected toxicity, immediate medical attention should be sought. Patients should be advised to take Auvelity exactly as prescribed and not to increase doses without healthcare provider guidance.

Disclaimer

The information provided in this document is for educational purposes only and does not constitute medical advice. It is essential to consult with a qualified healthcare professional for any health concerns or before making any decisions related to your health or treatment.