Adverse effects of opioids prescribed in opioid agonist treatment: a systematic review protocol

Background: Opioid agonist treatment (OAT) comprises the use of opioid agonists to replace illicit street opioids and is the treatment of choice for individuals with opioid use disorder (OUD). We aim to systematically review the risk for any type of adverse effects of OAT in patients with opioid use disorder.Methods: We aim to inform evidence-based care decisions with a systematic review of published randomised controlled trials (RCTs) evaluating opioid agonists for the treatment of OUD in comparison to any control and reporting adverse effects. The search strategy was developed and peer-reviewed by medical information specialists. The databases Embase, Medline, PsycInfo, CENTRAL, and the Web of Science Core Collection will be searched without date limits. Title and abstract screening will be done in duplicate by three and full text screening by two independent reviewers. Data extraction will be checked by a second reviewer. Disagreements will be resolved by a third reviewer.We aim to combine study results in random-effects meta-analyses and calculate relative and absolute risks.Risk of bias will be assessed with version 2 of the Cochrane risk-of-bias tool for randomized trials (RoB 2).An assessment of quality of evidence will be conducted using the Grading of Recommendation, Assessment, Development and Evaluation (GRADE) framework.Discussion: The results of this systematic review will provide evidence to allow optimal clinical decision making for patients with OAT, in particular those with previous adverse events.