Neurocognitive impairments and brain abnormalities resulting from opioid-related overdoses: A systematic review

Background: Non-fatal opioid-related overdoses have increased significantly over the past two decades and there have been increasing reports of brain injuries and/or neurocognitive impairments following overdose events. Limited preclinical research suggests that opioid overdoses may cause brain injury; however, little is known about such injuries in humans. The purpose this systematic review is to summarize existing studies on neurocognitive impairments and/or brain abnormalities associated with an opioid-related overdose in humans.

Methods: PubMed, Web of Science, Ovid MEDLINE and PsyINFO were searched, without year restrictions, and identified 3099 articles. An additional 24 articles were identified by reviewing references. Articles were included if they were published in English, reported study findings in humans, included individuals 18 years of age or older, and reported an objective measure of neurocognitive impairments and/or brain abnormalities resulting from an opioid-related overdose. Six domains of bias (selection, performance, attrition, detection (two dimensions) and reporting were evaluated and themes were summarized.

Results: Seventy-nine journal articles, published between 1973-2020, were included in the review. More than half of the articles were case reports (n = 44) and there were 11 cohort studies, 18 case series, and 6 case-control studies. All of the studies were categorized as at-risk of bias, few controlled for confounding factors, and methodological differences made direct comparisons difficult. Less than half of the studies reported toxicology results confirming an opioid-related overdose; 64.6 % reported brain MRI results and 27.8 % reported results of neuropsychological testing. Only two studies had within subject comparative data to document changes in the brain possibly associated with an overdose. Despite these limitations, existing publications suggest that brain injuries and neurocognitive impairments are associated with opioid overdose. Additional research is needed to establish the incidence of overdose-related brain injuries and the potential impact on functioning, as well as engagement in treatment of substance use disorders.

Conclusions: Respiratory depression is a defining characteristic of opioid overdose and prolonged cerebral hypoxia may cause brain injuries and/or neurocognitive impairments. The onset, characteristics, and duration of such injuries is variable and additional research is needed to understand their clinical implications.