Dextromethorphan-Bupropion Effective for Comorbid Anxiety, Major Depressive Disorder

Treatment with AXS-05 rapidly reduces anxiety symptoms in patients with major depressive disorder.

Treatment with dextromethorphan-bupropion (AXS-05) was found to be safe and effective for anxiety among patients with major depressive disorder (MDD) and a history of treatment failure, according to study results presented at Psych Congress 2022, held virtually from September 17 to 20, 2022.

A gap in effective treatment for MDD remains a significant unmet clinical need, with approximately one-third of patients achieving remission with selective serotonin reuptake inhibitors. Comorbid anxiety is reported by approximately half of patients with MDD and can be more difficult to treat than symptoms of depression alone.

The Evaluation of NMDA Modulation for Depressive Episodes (EVOLVE) study was an open-label trial conducted among patients with MDD. All included patients reported anxiety symptoms and had received treatment with at least 1 antidepressant for their current MDD episode. Patients received AXS-05 (45 mg/100 mg) twice daily for up to 15 months. Efficacy endpoints included changes in Hamilton Anxiety Rating Scale (HAM-A) and Montgomery-Asberg Depression Rating Scale (MADRS) scores from baseline.

Among patients included in the final analysis (n=146), 60.7% were women, the mean age was 45.6 (SD, 13.07) years, 77.2% were White, the mean MADRS score at baseline was 32.2 (SD, 4.14), and the mean HAM-A score at baseline was 15.6 (SD, 5.56).

These data provide additional evidence for the efficacy of AXS-05 in MDD including those with prior treatment failures and those with anxious features.

After 1 week of treatment HAM-A scores among the patients had decreased significantly (mean, 12.3; P <.001), with further decreases in scores observed through month 12 (mean, 4.6; P <.001).

Anxiety remission, defined as a HAM-A score of less than 7, was achieved after a mean of 6 weeks of treatment with AXS-05. At month 12, 78.3% of the patients had achieved anxiety remission. Response to AXS-05, defined as a 50% or greater improvement in HAM-A scores from baseline, was observed among 77.1% of the patients at month 12.

Adverse events occurred among 64.4% of the patients, the most common of which included COVID-19 infection (8.9%), nausea (8.9%), headache (7.5%), dry mouth (6.2%), dizziness (5.5%), and insomnia (5.5%). In addition, 8.9% of patients discontinued treatment with AXS-05 due to adverse events.

This study was limited by its open-label design and the lack of a comparator cohort.

Study authors concluded, “Response and remission from anxiety symptoms were achieved as early as 1 week after starting treatment with AXS-05. These data provide additional evidence for the efficacy of AXS-05 in MDD including those with prior treatment failures and those with anxious features.”

Disclosure: Multiple authors declared affiliations with industry. Please see the original reference for a full list of disclosures.


Jones A, Streicher C, Thomas Z, Alter S, Tabuteau H. Improvement in anxiety symptoms in depressed patients treated with AXS-05 (dextromethorphan-bupropion): results from the EVOLVE open-label, long-term study. Abstract presented at at: Psych Congress 2022; September 17-20, 2022. Abstract 149.