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

E. Ostinelli, G. Salanti, Malcolm R. Macleod, V. Chiocchia, Katharine A. Smith, A. Stringaris, J. Downs, Emma S. J. Robinson et al.

EBioMedicine, 2025

2,076 participants · 10 citations

Abstract

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

How strong is the evidence?

Evidence Hub reads this as a meta-analysis, done in people. Its evidence level is 1 of 5 (Highest · pooled evidence). Pooled evidence from several studies sits at the top of the evidence pyramid. Reported size: 2,076 participants or records.

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