Harmful Effects of Prescribed Opioids in Children and Adults: A Systematic Review

Background: Opioids are commonly used to manage both acute and chronic pain by acting on opioid receptors in the central and peripheral nervous systems. However, concerns about their increasing prescription and misuse have emerged due to adverse effects, toxicity, and the global impact of opioid-related harm. Objectives: This systematic review aims to evaluate the harmful (adverse and toxic) effects of prescribed opioids on the pediatric and the general population. Methods: Following PRISMA guidelines, a systematic search was conducted for data from January 2011 to December 2024 across selected electronic databases (PubMed^®, SciELO^®, Web of Science^®, and EMBASE^®) using a specific search strategy with Boolean operators. Cross-sectional, cohort, and case-control designs published in English, analyzing and identifying the harmful effects of prescribed opioids in children and the general population, were eligible for inclusion. Three reviewers independently assessed titles and abstracts for eligibility, followed by a full-text review. A referee reviewer resolved discrepancies. Data extraction was performed for qualifying studies. The risk of bias was assessed by the ROBINS-I tool. Results: A total of 3984 papers were collected, with 1697 duplicates and 2062 non-eligible papers removed; resulting in 25 papers (112.825 patients) selected for qualitative analysis. The pediatric group experienced more harmful effects across multiple body systems (nausea and vomiting, hypotension, agitation, drowsiness/lethargy, lethargy, respiratory depression, aspiration pneumonia) compared to the general population (dominant S wave, long QTc interval, right axis deviation, seizure). Conclusions: Despite the data heterogeneity, this study highlights the importance of evaluating the harmful effects of opioids, particularly in pediatric patients, to assess the risk-benefit balance and health risks associated with their use. The lower number of effects in the general population may be attributed to increased pharmacological tolerance and tolerability.