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Dopamine partial agonists and prodopaminergic drugs for schizophrenia: Systematic review and meta-analysis of randomized controlled trials

Lookup NU author(s): Dr Leigh TownsendORCiD

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Abstract

Dopaminergic dysfunction is thought to be central to schizophrenia symptomatology. Previous meta-analyses of prodopaminergic drugs in schizophrenia have important limitations, and also did not include dopamine D2/D3 partial agonists. We investigated the effect of medications which increase dopamine signalling on schizophrenia symptoms by meta-analysing double-blind, placebo-controlled RCTs. 59 RCTs were included: 29 of prodopaminergic treatments, 30 of partial agonists. Partial agonists were significantly superior to placebo against positive (SMD=-0.33,p = 1.2 ×10^-17), negative (SMD=-0.29,p = 2.2 × 10-³¹) and total symptoms (SMD =-0.39,p = 1.7 × 10^-30) in schizophrenia. There were no significant differences between pooled pro-dopaminergic drugs and placebo in any symptom domain. In subgroup analysis of five studies where patients were selected for negative symptom severity, ar/modafinil was superior to placebo against negative symptoms (SMD=-0.34,p = 0.037). These data favour the clinical use of partial agonists for negative symptoms in schizophrenia, with clinically meaningful effect sizes. Our findings also suggest a benefit for ar/modafinil in patients with predominant negative symptoms. Future trials of other prodopaminergic therapies and dopamine partial agonists in patients with predominant negative symptoms are warranted.

Publication metadata

Author(s): Osugo M, Whitehurst T, Shatalina E, Townsend L, O'Brien O, Mak T, McCutcheon R, Howes O

Publication type: Article

Publication status: Published

Journal: Neuroscience and Biobehavioural Reviews

Year: 2022

Volume: 135

Print publication date: 01/04/2022

Online publication date: 04/02/2022

Acceptance date: 02/02/2022

ISSN (print): 0149-7634

ISSN (electronic): 1873-7528

Publisher: Elsevier Ltd

URL: https://doi.org/10.1016/j.neubiorev.2022.104568

DOI: 10.1016/j.neubiorev.2022.104568

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