Trial reportThe international journal of neuropsychopharmacology2025
Antidepressant efficacy of ketamine plus naltrexone for major depression comorbid with alcohol use disorder: a randomized controlled trial.
Trial report in The international journal of neuropsychopharmacology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT02461927 (Ketamine for The Rapid Treatment of Major Depression and Alcohol Use Disorder), which is not on this map. Cited by 8 papers, 3 of them syntheses that pooled it.
What it found
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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.
Ketamine for The Rapid Treatment of Major Depression and Alcohol Use Disorder
Who cites it
8 citing papers in PubMed, 3 syntheses or guidelines pooled it.
- Is the antidepressant efficacy of ketamine and esketamine mediated via opioid mechanisms?European psychiatry : the journal of the Association of European Psychiatrists · 2026Pooled it
- Ketamine for substance use disorders: a systematic review and meta-analysis.Frontiers in psychiatry · 2026Pooled it
- Psychiatric Association of Türkiye Mood Disorders Section Depression Treatment Guideline - III: Treatment Approach for Depression Subtypes and Special Groups, Psychotherapies, and Psychosocial Interventions.Turk psikiyatri dergisi = Turkish journal of psychiatry · 2026Guideline
- Pleiotropic modulation of the gut-brain-lung axis by ketamine and its enantiomers.Molecular psychiatry · 2026Review
- Clinical evaluation of adjunctive magnesium therapy in patients receiving antidepressants for depression-open label, nonrandomized clinical trial.Naunyn-Schmiedeberg's archives of pharmacology · 2026Article
- Kava (Nutrients · 2026Review
- The Role of Exosomes in the Regulation of Molecular Mechanisms Underlying Treatment Resistance-Linking Cellular Crosstalk to Clinical Implications in Depression.International journal of molecular sciences · 2026Review
- Methodological considerations for interpreting ketamine-naltrexone trials in depression.The international journal of neuropsychopharmacology · 2025Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
5 authors.
Funding
Abstract
importanceThe comorbidity of major depressive disorder (MDD) and alcohol use disorder (AUD) is often treated inadequately. This study evaluated the impact of adding the opioid receptor blocker, naltrexone, to the NMDA glutamate receptor antagonist, ketamine, for the treatment of MDD comorbid with AUD. In so doing, it also attempted to shed light on the contribution of opioid receptor stimulation to the antidepressant effects of ketamine in this population.
objectiveTo compare the efficacy of ketamine plus naltrexone to ketamine plus saline and midazolam plus saline for reducing depression and decreasing alcohol consumption in outpatients with comorbid MDD and AUD. DESIGN, SETTING, AND
participantsA 3-arm, randomized, double-blind, parallel-group study was conducted. Participants were 65 adults with current MDD and AUD, with Montgomery-Åsberg Depression Rating Scale (MADRS) total score of 20 or higher and heavy drinking at least 4 times in the month prior to randomization.
interventionsRandomized (1:1:1) to receive (1) intravenous (IV) ketamine (0.5 mg/kg) once a week for 4 weeks (a total of 4 infusions) plus intramuscular (IM) naltrexone (380 mg), (2) IV ketamine plus IM saline, or (3) IV midazolam (0.045 mg/kg) plus IM saline. MAIN OUTCOMES AND MEASURES: Co-primary: MADRS; complete alcohol abstinence. Secondary: alcohol craving, anxiety, quality of life, safety.
resultsOf 65 participants, 58 received at least 1 ketamine/midazolam infusion: 20 in ketamine-naltrexone, 19 in ketamine-saline, 19 in midazolam-saline. All groups improved significantly (>80% depression remission). No group differences were observed in MADRS changes during treatment (primary outcome), although antidepressant effects persisted longer in ketamine groups compared to midazolam. There were no significant group differences in alcohol-related outcomes. Ketamine groups showed greater improvement in anxiety and quality of life (secondary outcomes) than midazolam, with the ketamine-naltrexone group showing greater improvement in anxiety than ketamine-saline. No study-related serious adverse events. CONCLUSIONS AND RELEVANCE: This study found similar antidepressant and anti-alcohol effects across 3 groups. Compared to midazolam, the ketamine groups showed longer-lasting antidepressant effects and greater improvements in anxiety and quality of life. Comparable outcomes between the 2 ketamine groups suggest opioid receptor antagonism did not alter ketamine's therapeutic effects. CLINICAL
trial registrationThe study was registered at ClinicalTrials.gov (Identifier: NCT02461927).
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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 OpenQuestion graph.