1. Dopamine partial agonists and prodopaminergic drugs for schizophrenia: Systematic review and meta-analysis of randomized controlled trials.
- Author
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Osugo M, Whitehurst T, Shatalina E, Townsend L, O'Brien O, Mak TLA, McCutcheon R, and Howes O
- Subjects
- Dopamine, Dopamine Agonists therapeutic use, Humans, Randomized Controlled Trials as Topic, Antipsychotic Agents therapeutic use, Schizophrenia drug therapy
- 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., (Copyright © 2022 Elsevier Ltd. All rights reserved.)- Published
- 2022
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