Trial reportNeuropsychopharmacology : official publication of the American College of Neuropsychopharmacology2015
Evaluation of opioid modulation in major depressive disorder.
Trial report in Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 81 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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
81 citing papers in PubMed, 2 syntheses or guidelines pooled it, 173 citations in OpenAlex.
- The efficacy and safety of buprenorphine for the treatment of depression: A systematic review and meta-analysis.Journal of psychiatric research · 2023Pooled it
- The Efficacy of Buprenorphine in Major Depression, Treatment-Resistant Depression and Suicidal Behavior: A Systematic Review.International journal of molecular sciences · 2018Pooled it
- Efficacy and safety of aticaprant, a kappa receptor antagonist, adjunctive to oral SSRI/SNRI antidepressant in major depressive disorder: results of a phase 2 randomized, double-blind, placebo-controlled study.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2024Trial
- Opioid system modulation with buprenorphine/samidorphan combination for major depressive disorder: two randomized controlled studies.Molecular psychiatry · 2020Trial
- Results from a long-term open-label extension study of adjunctive buprenorphine/samidorphan combination in patients with major depressive disorder.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2019Trial
- Polymorphism A118G of opioid receptor mu 1 (OPRM1) is associated with emergence of suicidal ideation at antidepressant onset in a large naturalistic cohort of depressed outpatients.Scientific reports · 2019Trial
- Effects of Buprenorphine on Responses to Emotional Stimuli in Individuals with a Range of Mood Symptomatology.The international journal of neuropsychopharmacology · 2018Trial
- Association Between Placebo-Activated Neural Systems and Antidepressant Responses: Neurochemistry of Placebo Effects in Major Depression.JAMA psychiatry · 2015Trial
- Navacaprant, a Novel and Highly Selective Kappa Opioid Receptor Antagonist, in Adults With Major Depressive Disorder: A Randomized, Double-Blind Phase 2 Clinical Trial.Journal of clinical psychopharmacologyTrial
- Review
- Updated Freudian drive theory: childhood trauma, epigenetics, serotonin and beta endorphin.Frontiers in psychiatry · 2026Article
- Emerging Medications for Treatment-Resistant Depression: A Review with Perspective on Mechanisms and Challenges.Brain sciences · 2025Review
- Neuropeptidergic systems in psychiatric disorders.Frontiers in endocrinology · 2025Review
- Emerging pharmacological targets for alcohol use disorder.Alcohol (Fayetteville, N.Y.) · 2024Review
- Classics in Chemical Neuroscience: Tianeptine.ACS chemical neuroscience · 2024Review
- Prescription opioid dispensing patterns among patients with schizophrenia or bipolar disorder.BMC psychiatry · 2024Observational
- Therapeutic Potential of Buprenorphine in Depression: A Meta-Analysis of Current Evidence.Journal of clinical medicine research · 2024Article
- Opioid Mechanisms and the Treatment of Depression.Current topics in behavioral neurosciences · 2024Review
- A Review of Therapeutics for Treatment-Resistant Depression in the Older Adult.Drugs & aging · 2023Review
- Cross-phenotype relationship between opioid use disorder and suicide attempts: new evidence from polygenic association and Mendelian randomization analyses.Molecular psychiatry · 2023Article
21 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
7 authors at 3 institutions in 1 country.
Funding
Abstract
Although opioids have known antidepressant activity, their use in major depressive disorder (MDD) has been greatly limited by risk of abuse and addiction. Our aim was to determine whether opioid modulation achieved through a combination of a μ-opioid partial agonist, buprenorphine (BUP), and a potent μ-opioid antagonist, samidorphan (SAM), would demonstrate antidepressant activity without addictive potential. A placebo-controlled crossover study assessed the opioid pharmacodynamic profile following escalating doses of SAM co-administered with BUP in opioid-experienced adults. A subsequent 1-week, placebo-controlled, parallel-group study was conducted in subjects with MDD and an inadequate response to standard antidepressant therapy. This second study evaluated safety and efficacy of ratios of BUP/SAM that were associated with partial and with maximal blockade of opioid responses in the initial study. Pupillometry, visual analog scale assessments, and self-reported questionnaires demonstrated that increasing amounts of SAM added to a fixed dose of BUP resulted in dose-dependent reductions in objective and subjective opioid effects, including euphoria and drug liking, in opioid-experienced adults. Following 7 days of treatment in subjects with MDD, a 1 : 1 ratio of BUP and SAM, the ratio associated with maximal antagonism of opioid effects, exhibited statistically significant improvement vs placebo in HAM-D17 total score (p=0.032) and nearly significant improvement in Montgomery-Åsberg Depression Rating Scale (MADRS) total score (p=0.054). Overall, BUP/SAM therapy was well tolerated. A combination of BUP and SAM showed antidepressant activity in subjects with MDD. Balanced agonist-antagonist opioid modulation represents a novel and potentially clinically important approach to the treatment of MDD and other psychiatric disorders.
Indexed as
Identifiers
What OpenQuestion 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 OpenQuestion graph.