Evidence map›Paper›PMID 41168072›Full record

SynthesisEBioMedicine2025

Pro-dopaminergic pharmacological interventions for anhedonia in depression: a living systematic review and network meta-analysis of human and animal studies.

Edoardo G Ostinelli, Georgia Salanti, Malcolm Macleod, Virginia Chiocchia, Katharine A Smith, Argyris Stringaris, James Downs, Emma Sj Robinson, Gin S Malhi, Dominic M Dwyer and 9 more

Erratum issuedAbstract readSystematic ReviewNetwork Meta-Analysis
PubMed Full text at PMC Publisher
In one paragraph

Synthesis in EBioMedicine, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 6 papers.

0numbers the graph read from it
0cells of the map it votes in
6citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from 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.

2 · The registry

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.

3 · Its place in the literature

Who cites it

6 citing papers in PubMed.

  1. Review
  2. Article
  3. Article
  4. Article
  5. Article
  6. Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

19 authors.

Edoardo G OstinelliDepartment of Psychiatry, University of Oxford, Oxford, UK; NIHR Oxford Health Clinical Research Facility, Oxford Health NHS Foundation Trust, Warneford Hospital, Oxford, UK; Oxford Precision Psychiatry Lab, NIHR Oxford Health Biomedical Research Centre, Oxford, UK.
Georgia SalantiInstitute of Social and Preventive Medicine, University of Bern, Switzerland.
Malcolm MacleodCentre for Clinical Brain Sciences, University of Edinburgh, UK.
Virginia ChiocchiaInstitute of Social and Preventive Medicine, University of Bern, Switzerland.
Katharine A SmithDepartment of Psychiatry, University of Oxford, Oxford, UK; NIHR Oxford Health Clinical Research Facility, Oxford Health NHS Foundation Trust, Warneford Hospital, Oxford, UK; Oxford Precision Psychiatry Lab, NIHR Oxford Health Biomedical Research Centre, Oxford, UK.
Argyris StringarisFaculty of Brain Sciences, University College London, UK; First Department of Psychiatry, Aiginiteion Hospital, National and Kapodistrian University of Athens, Greece.
James DownsMQ Mental Health Research, London, UK.
Emma Sj RobinsonSchool of Physiology, Pharmacology & Neuroscience, University of Bristol, UK.
Gin S MalhiDepartment of Psychiatry, University of Oxford, Oxford, UK; Academic Department of Psychiatry, Kolling Institute, Northern Clinical School, Faculty of Medicine and Health, The University of Sydney, Australia; CADE Clinic and Mood-T, Royal North Shore Hospital, Northern Sydney Local Health District, St Leonards, Australia.
Dominic M DwyerSchool of Psychology, Cardiff University, Cardiff, UK.
Astrid ChevanceUniversité Paris Cité and Université Sorbonne Paris Nord, Inserm, INRAE, Center for Research in Epidemiology and StatisticS (CRESS), Paris, France; Centre d'Epidémiologie Clinique, AP-HP, Hôpital Hôtel Dieu, F-75004, Paris, France.
Christoph U CorrellDepartment of Psychiatry, Zucker Hillside Hospital, Northwell Health, New York, USA; Department of Child and Adolescent Psychiatry, Charité Universitätsmedizin Berlin, Germany.
Thomy ToniaInstitute of Social and Preventive Medicine, University of Bern, Switzerland.
Emily WheelerMQ Mental Health Research, London, UK.
Toshi A FurukawaKyoto University Office of Institutional Advancement and Communications, Kyoto, Japan.
Diego A PizzagalliDepartment of Psychiatry, University of Oxford, Oxford, UK; Noel Drury, M.D. Institute for Translational Depression Discoveries, University of California, Irvine, CA, USA.
Michael BrowningDepartment of Psychiatry, University of Oxford, Oxford, UK; NIHR Oxford Health Clinical Research Facility, Oxford Health NHS Foundation Trust, Warneford Hospital, Oxford, UK.
Jennifer PottsDepartment of Psychiatry, University of Oxford, Oxford, UK; Oxford Precision Psychiatry Lab, NIHR Oxford Health Biomedical Research Centre, Oxford, UK.
Andrea CiprianiDepartment of Psychiatry, University of Oxford, Oxford, UK; NIHR Oxford Health Clinical Research Facility, Oxford Health NHS Foundation Trust, Warneford Hospital, Oxford, UK; Oxford Precision Psychiatry Lab, NIHR Oxford Health Biomedical Research Centre, Oxford, UK. Electronic address: andrea.cipriani@psych.ox.ac.uk.

Funding

Project 4_Bruchas : Circuit-level Approaches for Dissecting Approach/Avoidance Behaviors Mediated by Nociceptin Systems in MiceP50MH119467 · NIMH · MCLEAN HOSPITAL · PI PIZZAGALLI, DIEGO A · 2020 to 2024
$15.9M
Neuroimaging Studies of Reward Processing in DepressionR37MH068376 · NIMH · UNIVERSITY OF CALIFORNIA-IRVINE · PI Diego A Pizzagalli · 2016 to 2026
$7.4M
NIMH NIH HHS P50 MH119467NIMH NIH HHS R37 MH068376
6 · The paper itself

Abstract

backgroundIt is unclear whether pro-dopaminergic drugs reduce anhedonia in major depressive disorder (MDD) and further, if so, to what extent this is the case.

methodsWith lived experienced experts we co-produced two living systematic reviews of randomised controlled trials (RCTs) investigating the relative efficacy of pro-dopaminergic interventions in reducing symptoms of anhedonia in people with MDD (versus placebo) and in relevant non-human animal models (versus vehicle control/no intervention). Multiple electronic databases were searched until June 9, 2024. The primary outcomes were subjective anhedonia symptoms in humans and sucrose preference test (a measure of reward sensitivity and proxy for anhedonia) in animals. We evaluated other important domains and clinical aspects closely related to anhedonia, such as reward/reinforcement tasks, anxiety symptoms, acceptability, tolerability, and adverse events. We performed pairwise meta-analyses separately for human and non-human studies. We also estimated the relative effects of pro-dopaminergic versus non-dopaminergic antidepressants in human studies on anhedonia and overall depressive symptoms using a series of random-effects network meta-analyses of both aggregate and patient-level data. A multidisciplinary panel of international experts (including people with lived experience) then interpreted the overall results and produced a list of recommendations via a triangulation process. This study is part of GALENOS (Global Alliance for Living Evidence in aNxiety, depressiOn, and pSychosis). PROSPERO registration: CRD42023451821.

findingsPro-dopaminergic interventions were associated with a small reduction of anhedonia symptoms (6 RCTs, n = 2076; SMD -0.24, 95% CI -0.46 to -0.03) in people with MDD and increased sucrose preference in animal models (27 RCTs; SMD 1.34, 0.88 to 1.79). We did not find data about reward/reinforcement tasks in humans. Evidence was rated as low to moderate. In the network meta-analysis, some antidepressants with a non-dopaminergic mechanism of action showed reduction in anhedonia symptoms, which was larger than pro-dopaminergic drugs and probably independent of overall depression improvement.

interpretationOur findings provide some support for the role of dopamine in anhedonia. However, the precise neurobiological mechanisms of anhedonia in major depression are still poorly understood and we posit that they may be possibly related to altogether different or more general effects of antidepressants on these symptoms. Therefore, data on reward, including reward-related learning and memory, are needed to properly examine the relationship between dopamine modulation and anhedonia.

fundingWellcome (GALENOS project).

Indexed as

AnhedoniaAntidepressive AgentsDepressionDopamineMajor Depressive DisorderAnimalsDisease Models, AnimalHumansAntidepressive AgentsDopamineAnhedoniaDopamineLiving systematic reviewMajor depressionMeta-analysis

Identifiers

PMID41168072
PMCPMC12790147

What OpenQuestion holds

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Registered trials

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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.