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

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Ostinelli, Edoardo G , Salanti, Georgia , Macleod Malcolm , Chiocchia, Virginia , Smith, Katharine A , Stringaris, Argyris , Downs, James , Robinson, Emma Sj , Malhi Gin S , Dwyer, Dominic M , Chevance Astrid , Correll, Christoph U. , Tonia, Thomai , Wheeler, Emily , Furukawa, Toshi A. , Pizzagalli, Diego A. , Browning, Michael , Potts, Jennifer , Cipriani Andrea ·

YOU? · · 2025 · Open Access · · DOI: https://doi.org/10.48620/92289

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 (Global Alliance for Living Evidence in aNxiety, depressiOn, and pSychosis). PROSPERO registration: CRD42023451821.Findings Pro-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.Interpretation Our 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.Funding Wellcome (GALENOS project).

Related Topics

Medicine

Psychiatry

Anxiety

Major Depressive Disorder

Randomized Controlled Trial

Concepts

Anhedonia Psychological intervention Clinical psychology Medicine Psychiatry Anxiety Major depressive disorder Psychology Randomized controlled trial Systematic review Clinical Global Impression Clinical trial Placebo Mood Pairwise comparison PsycINFO Quality of life (healthcare) Human studies Depression (economics) Psilocybin Novelty Adverse effect Rating scale

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

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Authors: Ostinelli, Edoardo G, Salanti, Georgia, Macleod Malcolm, Chiocchia, Virginia, Smith, Katharine A, Stringaris, Argyris, Downs, James, Robinson, Emma Sj, Malhi Gin S, Dwyer, Dominic M, Chevance Astrid, Correll, Christoph U., Tonia, Thomai, Wheeler, Emily, Furukawa, Toshi A., Pizzagalli, Diego A., Browning, Michael, Potts, Jennifer, Cipriani Andrea

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Concepts: Anhedonia, Psychological intervention, Clinical psychology, Medicine, Psychiatry, Anxiety, Major depressive disorder, Psychology, Randomized controlled trial, Systematic review, Clinical Global Impression, Clinical trial, Placebo, Mood, Pairwise comparison, PsycINFO, Quality of life (healthcare), Human studies, Depression (economics), Psilocybin, Novelty, Adverse effect, Rating scale

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