SynthesisCNS drugs2023
Dextromethorphan-Bupropion for the Treatment of Depression: A Systematic Review of Efficacy and Safety in Clinical Trials.
Synthesis in CNS drugs, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers, 1 of them a synthesis that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
14 citing papers in PubMed, 1 synthesis or guideline pooled it, 30 citations in OpenAlex.
- Dextromethorphan Beyond the Cough: Exploring Its Psychedelic Potential: A Systematic Review.CNS drugs · 2026Pooled it
- Treatment-resistant Depression in the Post-ketamine Era: Unmet Needs beyond Rapid Response.Clinical psychopharmacology and neuroscience : the official scientific journal of the Korean College of Neuropsychopharmacology · 2026Review
- Synaptic Plasticity-Intrinsic Excitability and Antidepressant Discovery.Biomedicines · 2026Review
- Psychedelics: Future Therapeutics in Major Depression?Advances in experimental medicine and biology · 2026Review
- Review
- The Pathogenesis and Medical Treatment of Depression: Opportunity and Challenge.Neurology international · 2025Review
- Post-market safety profile and suicide/self-injury risk signals of dextromethorphan/bupropion: a real-world pharmacovigilance study.European journal of clinical pharmacology · 2025Article
- Addressing blinding in classic psychedelic studies with innovative active placebos.The international journal of neuropsychopharmacology · 2025Review
- Can dextromethorphan-bupropion reduce mental pain in depressed individuals? A generating hypothesis overview perspective.Annals of general psychiatry · 2025Review
- Advancing depression treatment: the role of sigma receptor ligands.Frontiers in neuroscience · 2025Review
- Future Therapeutic Strategies for Alzheimer's Disease: Focus on Behavioral and Psychological Symptoms.International journal of molecular sciences · 2024Review
- NMDA Receptor Antagonists: Emerging Insights into Molecular Mechanisms and Clinical Applications in Neurological Disorders.Pharmaceuticals (Basel, Switzerland) · 2024Review
- Article
- Efficacy, Safety, and Tolerability of Psychedelics in Treatment-Resistant Depression (TRD).Advances in experimental medicine and biology · 2024Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
10 authors at 6 institutions in 4 countries.
Funding
Abstract
backgroundA significant proportion of adults with major depressive disorder (MDD) do not respond to treatments which are currently used in clinical practice such as first-generation monoamine-based antidepressants.
objectivesThe objective of this systematic review was to assess the efficacy, safety, and mechanisms of action of AXS-05, a combination of the NMDA-receptor antagonist dextromethorphan with bupropion, in adults with MDD.
methodsWe searched PubMed, Embase, Google Scholar, and ClinicalTrials.gov for current studies reporting on efficacy and/or safety of AXS-05 in patients with MDD. The search terms included: "AXS-05" OR "dextromethorphan and bupropion" AND "depression". Studies from database inception to January 2023 were evaluated. Risk of bias was assessed using the Cochrane Risk of Bias tool.
resultsThe search yielded 54 studies of which 5 were included. All studies had low risk of bias. Depression severity, measured with the Montgomery-Åsberg Depression Rating Scale (MADRS) significantly decreased as early as 1-week post-treatment from baseline when compared to a placebo-controlled group (LS mean difference 2.2; 95% CI 0.6-3.9; p = 0.007) and at 2 weeks compared to an active control group (LS mean difference 4.7; 95% CI 0.6-8.8; p = 0.024). Treatment efficacy could be maintained for up to 12 months with mean MADRS score reduction of 23 points from baseline. Clinical remission and response rates also improved at week 1 and were maintained for 12 months. The treatment was well-tolerated, with some transient adverse events reported.
conclusionCurrent evidence suggests that the combination of dextromethorphan and bupropion is a well-tolerated, rapid-acting treatment option for adults with MDD. Initial success with AXS-05 supports the mechanistic role of glutamatergeric and sigma 1 signaling in the pathophysiology of MDD.
Indexed as
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What Socratic holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.