Pro-dopaminergic pharmacological interventions for anhedonia in depression: protocol for a living systematic review of human and non-human studies.

Ostinelli, Edoardo G; Chiocchia, Virginia; Macleod, Malcolm; Browning, Michael; Harmer, Catherine; Siafis, Spyridon; Stansfield, Claire; Friedrich, Claire; Wright, Simonne; Chikaura, Tanatswa; Milligan, Lea; Thomas, James; Moreno, Carmen; Furukawa, Toshi A; Seedat, Soraya; Potts, Jennifer; Salanti, Georgia; Cipriani, Andrea (2023). Pro-dopaminergic pharmacological interventions for anhedonia in depression: protocol for a living systematic review of human and non-human studies. Wellcome open research, 8, p. 425. Wellcome Trust 10.12688/wellcomeopenres.19870.1

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Background: Anhedonia is a key symptom of depression, and it has been suggested as a potential target for future individualised treatments. However, much is unknown about how interventions enhancing dopaminergic pathways may affect anhedonia symptoms in the context of depression. Methods: We will perform independent searches in multiple electronic databases to identify clinical and animal experimental studies on pro-dopaminergic interventions in individuals with depression or animal models for depression. The primary outcomes will be overall anhedonia symptoms and their behavioural proxies in animals. Secondary outcomes will include side effects and neurobiological measures. At least two independent reviewers will conduct the study selection, data extraction, and risk of bias assessments using pre-defined tools according to each record's study design. We will develop ontologies to facilitate study identification and data extraction. We will synthesise data from clinical and animal studies separately. If appropriate, we will use random-effects meta-analyses, or synthesis without meta-analyses. We will investigate study characteristics as potential sources of heterogeneity. We will evaluate the confidence in the evidence for each outcome and source of evidence, considering the summary of the association, potential concerns regarding internal and external validity, and reporting biases. When multiple sources of evidence are available for an outcome, we will draw an overall conclusion in a triangulation meeting involving a multidisciplinary team of experts. We plan updates of the review every 6 months, and any future modifications to the protocol will be documented. We will co-produce this review with multiple stakeholders. PROSPERO registration: CRD42023451821.

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