Trial reportNeurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics2020
The Antidiabetic Metformin as an Adjunct to Antidepressants in Patients with Major Depressive Disorder: A Proof-of-Concept, Randomized, Double-Blind, Placebo-Controlled Trial.
Trial report in Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It has been retracted, and should not be counted. It is linked to trial NCT04088448 (The Antidiabetic Metformin as a Novel Adjunct to Antidepressants in Major Depressive Disorder Patients), which is not on this map. Cited by 24 papers, 2 of them syntheses 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.
The Antidiabetic Metformin as a Novel Adjunct to Antidepressants in Major Depressive Disorder Patients: A Proof-of-Concept, Randomized, Double-Blind, Placebo-Controlled Trial
Who cites it
24 citing papers in PubMed, 2 syntheses or guidelines pooled it, 38 citations in OpenAlex.
- Mitochondrial-inflammation crosstalk in major depressive disorder: molecular mechanisms and therapeutic implications.Molecular psychiatry · 2026Pooled it
- Comparing the effect of fluoxetine, escitalopram, and sertraline, on the level of BDNF and depression in preclinical and clinical studies: a systematic review.European journal of clinical pharmacology · 2024Pooled it
- Effect of Perioperative Subanesthetic Dose of Esketamine on Postoperative Recovery Quality in Patients Undergoing Laparoscopic Gastrointestinal Surgery: A Randomised, Double-Blind, Controlled Trial.Drug design, development and therapy · 2025Trial
- Efficacy of empagliflozin as adjunctive therapy to citalopram in major depressive disorder: a randomized double-blind, placebo-controlled clinical trial.BMC psychiatry · 2024Trial
- Double-blind, randomized, placebo-controlled pilot study of the phosphodiesterase-3 inhibitor cilostazol as an adjunctive to antidepressants in patients with major depressive disorder.CNS neuroscience & therapeutics · 2021Trial
- Review
- Efficacy and Safety of Antidiabetic Agents for Major Depressive Disorder and Bipolar Depression: A Meta-Analysis of Randomized, Double-Blind, Placebo-Controlled Trials.Journal of clinical medicine · 2024Article
- Cool the Inflamed Brain: A Novel Anti-inflammatory Strategy for the Treatment of Major Depressive Disorder.Current neuropharmacology · 2024Review
- The Role of the Adrenal-Gut-Brain Axis on Comorbid Depressive Disorder Development in Diabetes.Biomolecules · 2023Review
- How does IL-6 change after combined treatment in MDD patients? A systematic review.Brain, behavior, & immunity - health · 2023Review
- The future of psychopharmacology: a critical appraisal of ongoing phase 2/3 trials, and of some current trends aiming to de-risk trial programmes of novel agents.World psychiatry : official journal of the World Psychiatric Association (WPA) · 2023Article
- Chronotherapeutic neuroprotective effect of verapamil against lipopolysaccharide-induced neuroinflammation in mice through modulation of calcium-dependent genes.Molecular medicine (Cambridge, Mass.) · 2022Article
- Are the antidepressant effects of insulin-sensitizing medications related to improvements in metabolic markers?Translational psychiatry · 2022Review
- Associations of Cardiovascular Agents and Metformin with Depression Symptoms: A Cross-Sectional Analysis from the HUNT Study, Norway.Drugs - real world outcomes · 2022Article
- Metformin for the Improvement of Comorbid Depression Symptoms in Diabetic Patients: A Systematic Review.Cureus · 2022Review
- Actions of Metformin in the Brain: A New Perspective of Metformin Treatments in Related Neurological Disorders.International journal of molecular sciences · 2022Review
- Changes in Mood, Anxiety, and Cognition with Polycystic Ovary Syndrome Treatment: A Longitudinal, Naturalistic Study.Neuropsychiatric disease and treatment · 2022Article
- Mechanisms affecting brain remodeling in depression: do all roads lead to impaired fibrinolysis?Molecular psychiatry · 2022Review
- Metformin for Cardiovascular Protection, Inflammatory Bowel Disease, Osteoporosis, Periodontitis, Polycystic Ovarian Syndrome, Neurodegeneration, Cancer, Inflammation and Senescence: What Is Next?ACS pharmacology & translational science · 2021Review
- Agmatine as a novel candidate for rapid-onset antidepressant response.World journal of psychiatry · 2021Review
Corrections and comments
- Retraction · 2022-09-07Concerns/Issues about Data · Concerns/Issues about Third Party Involvement · Unreliable Data · Unreliable Results and/or Conclusions ·
- Retracted
Authors and funding
7 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Metformin (MET) has been reported to have antidepressant effects in animal models and in diabetic patients with depression, owing to its anti-inflammatory, antioxidant, and neuroprotective activity. Accordingly, we proposed that MET would show antidepressant effects in patients with major depressive disorder (MDD) without other comorbidities. In this double-blind placebo-controlled study, 80 adult outpatients with MDD (DSM-IV criteria) and a Hamilton Depression Rating Scale (HAM-D) score >18 were randomized to receive fluoxetine 20 mg once daily plus placebo (n = 40) or fluoxetine 20 mg once daily plus MET 1000 mg once daily for 12 weeks. Patients were assessed by HAM-D score (weeks 0, 4, 8, and 12). The serum levels of TNF-α, IL-1β, IL-6, IGF-1, MDA, CRP, BDNF, and serotonin were measured before and after therapy. Mixed-effects model repeated-measures analysis of covariance was used to compare the HAM-D scores and the biological markers between the two groups. After 4, 8 and 12 weeks, patients in the MET group showed a statistically significant decline in HAM-D score relative to the placebo group (least squares mean difference [LSMD] -2.347, p = 0.000, LSMD -3.369, p = 0.000, and LSMD -3.454, p = 0.000, respectively). Response and remission rates were significantly higher in the MET group (89% and 81%, respectively) than in the placebo group (59% and 46%, respectively). Moreover, the MET group was superior in conserving the measured biological markers compared with the placebo group. Our findings suggest MET as a promising, effective, and safe short-term adjunctive approach in nondiabetic MDD patients. Trial registration ID: NCT04088448.
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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.