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Improvement in Anxiety Symptoms in Depressed Patients Treated With AXS-05 (DEXTROMETHORPHAN-BUPROPION): Results From the Evolve Open-Label, Long-Term Study
Open accessAbstract
Background: Innovative therapies to treat individuals with MDD, especially those with comorbid anxiety, are urgently needed. AXS-05 (dextromethorphan HBr 45 mg-bupropion HCl 105 mg) is a novel, oral, investigational NMDA receptor antagonist with multimodal activity. The dextromethorphan component of AXS-05 is an NMDA receptor antagonist and a sigma-1 receptor agonist. The bupropion component of AXS-05 serves primarily to increase the bioavailability of dextromethorphan. Objective: To evaluate the effects of AXS-05 on anxiety in MDD. Methods: EVOLVE was an open-label study, in which patients were treated with AXS-05 twice daily for up to 15 months. Subjects had either rolled in after a prior AXS-05 study or were directly enrolled and had a DSM-5 diagnosis of MDD, a MADRS score of ≥25, and had been treated with ≥ 1 antidepressant in the current major depressive episode. A total of 186 patients were enrolled. Efficacy endpoints included MADRS and HAM-A. Here we present the results for the directly enrolled patients (n =146). Results: Mean baseline HAM-A scores were 15.6. Reductions from baseline to Weeks 1, 2, and 6 were 3.4±5.34 (p< 0.001), 5.5±5.81 (p< 0.001), and 8.6±5.75 (p< 0.001), respectively. Improvements on the HAM-A were durable through Month 12 (-10.2±6.33; p< 0.001). Remission (HAM-A ≤7) rates on the HAM-A at Weeks 1, 2, and 6 were 19.9%, 36.0%, and 58.1%, respectively. Remission at Month 12 was 78.3%. Long-term treatment with AXS-05 was generally well tolerated. The most commonly reported adverse events were COVID-19 infection (8.9%), nausea (8.9%), headache (7.5%), dry mouth (6.2%), insomnia (5.5%), and dizziness (5.5%). Conclusions: These data support the use of AXS-05 in patients with comorbid depression and anxiety. Funding: Axsome Therapeutics
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“Similar to the COMET trial, clinical response and remission were achieved at month 12 by 81.9% and 67.5% of patients, respectively.”
From Dextromethorphan-bupropion (Auvelity) for the Treatment of Major Depressive Disorder (2023) · cites this paper as [22]
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“In both long-term studies, remission rates approached 70%, while response rates were greater than 80%.”
From Dextromethorphan-bupropion (Auvelity) for the Treatment of Major Depressive Disorder (2023) · cites this paper as [22]
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“Significant improvements were reported on MADRS total scores, Cognitive and Physical Functioning Questionnaire, Sheehan Disability Scale, and the Hamilton Anxiety Rating Scale.”
From Dextromethorphan-bupropion (Auvelity) for the Treatment of Major Depressive Disorder (2023) · cites this paper as [22]
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“Two long-term, open-label studies with dextromethorphan-bupropion saw large reductions in Montgomery–Åsberg Depression Rating Scale scores that were maintained through 12 and 15 months of treatment.”
From Dextromethorphan-bupropion (Auvelity) for the Treatment of Major Depressive Disorder (2023) · cites this paper as [22]
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“This will be important to replicate in larger RCTs, as co-occurring anxiety is a significant risk factor for TRD [158].”
From Pharmacotherapies Targeting GABA-Glutamate Neurotransmission for Treatment-Resistant Depression (2023) · cites this paper as [158]
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Dextromethorphan-bupropion (Auvelity) for the Treatment of Major Depressive Disorder
McCarthy, B., Bunn, H., Santalucia, M., Wilmouth, C., Muzyk, A., & Smith, C. M. (2023) · Clinical Psychopharmacology and Neuroscience · doi:10.9758/cpn.23.1081 · Cited by 63
Pharmacotherapies Targeting GABA-Glutamate Neurotransmission for Treatment-Resistant Depression
Vecera, C. M., C. Courtes, A., Jones, G., Soares, J. C., & Machado-Vieira, R. (2023) · Pharmaceuticals · doi:10.3390/ph16111572 · Cited by 48
“This will be important to replicate in larger RCTs, as co-occurring anxiety is a significant risk factor for TRD [158].”
Background
Metadata
- Authors
- Jones, A., Streicher, C., Alter, S., Thomas, Z., & Tabuteau, H.
- Affiliations
- Axsome Therapeutics (United States) (US)
- Venue
- CNS Spectrums
- Publisher
- Cambridge University Press (CUP)
- Published
- 2023-04
- Volume
- 28
- Issue
- 2
- Pages
- 260-260
- ISSN
- 1092-8529 (ISSN-L)
- 2165-6509
- OpenAlex
- W4365511218
- Cited by
- 5
- References
- 0
- Citations by year
- 2026: 1 · 2025: 1 · 2023: 2
- FWCI
- 0.62
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- CNS Spectrums (publishedVersion)
- Topics
- Health Sciences › Medicine › Pharmacology (medical) › Treatment of Major Depression
- Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmacology › Pharmacological Receptor Mechanisms and Effects
- Social Sciences › Psychology › Experimental and Cognitive Psychology › Anxiety, Depression, Psychometrics, Treatment, Cognitive Processes
- Keywords
- major depressive disorder, anxiety comorbidity, NMDA receptor antagonists, sigma-1 receptor agonist, long-term treatment, remission, Hamilton Anxiety Rating Scale, Montgomery-Asberg Depression Rating Scale, tolerability, adverse events, COVID-19 infection, headache, xerostomia, open-label extension
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- CoChat. (2026). Citation check: Improvement in Anxiety Symptoms in Depressed Patients Treated With AXS-05 (DEXTROMETHORPHAN-BUPROPION): Results From the Evolve Open-Label, Long-Term Study. https://app.cochat.ai/papers/10.1017/s1092852923002080
- The paper
- Jones, A., Streicher, C., Alter, S., Thomas, Z., & Tabuteau, H. (2023). Improvement in Anxiety Symptoms in Depressed Patients Treated With AXS-05 (DEXTROMETHORPHAN-BUPROPION): Results From the Evolve Open-Label, Long-Term Study. CNS Spectrums. https://doi.org/10.1017/s1092852923002080
