Regular Opioid Use for Chronic Pain Increases Risk for Dementia

Regular opioid use for chronic pain is associated with an increased risk for dementia and poorer brain health relative to non-opioid analgesic use, according to study results published in The American Journal of Geriatric Psychiatry.

The long-term neurological effects of regular opioid use remain largely unexplored. To examine the connection between regular opioid use and dementia outcomes, researchers conducted 3 studies using data from the United Kingdom Biobank database. The first prospective cohort study evaluated the risk for incident dementia following regular opioid use vs non-opioid analgesics among chronic pain patients. The second nested case-control study assessed the association between the number of opioid prescriptions issued in primary care and the risk for dementia. Additionally, the third cross-sectional study explored the relationship between regular opioid use and neuroimaging markers of brain health.

In the prospective cohort study, the researchers enrolled 129,793 participants with chronic pain, 23,178 of whom used opioids for pain management and 106,615 took non-opioid analgesics. The researchers then matched the patients with chronic pain with a control cohort of 71,280 participants, 17,820 of whom were using opioids and 53,460 used non-opioids. Over a 15-year follow-up, 2314 participants developed dementia. Relative to individuals who used non-opioid analgesics, opioid users had a higher 15-year cumulative incidence of dementia (4.60 vs 4.19 per 100 persons; P <.001) and regular opioid use was associated with an increased dementia risk (2.83 vs 2.40 per 1000 person-years; hazard ratio [HR] 1.18; P <.001). This association was consistent across subgroups and various adjustments did not change the results.

In the nested case-control study, 1560 individuals in the case group (those who had developed dementia) and 6582 individuals in the comparison group had received opioid prescriptions. The researchers found that the number of opioid prescriptions issued in primary care was significantly associated with dementia risk in a dose-dependent manner. The odds ratios (ORs) for developing incident dementia were as follows:

• 1 to 5 prescriptions: 1.21 (95% CI, 1.07-1.37, P =.003)
• 6 to 20 prescriptions: 1.27 (95% CI, 1.08-1.50, P =.003)
• More than 20 prescriptions: 1.43 (95% CI, 1.23-1.67, P <.001)

For non-opioid analgesics, the researchers did not observe a significant increase in dementia risk among individuals with up to 20 prescriptions.

Finally, results from the cross-sectional study indicated that regular opioid use was associated with lower total grey matter (P =.003) and hippocampal volumes (P =.008) and greater white matter hyperintensity volumes (P =.003) compared with those taking non-opioid analgesics.

The researchers concluded, “Overall, these findings imply a need for caution when prescribing opioids for chronic pain patients, and, if further evidence supports causality, provide insights into strategies to mitigate the burden of dementia.”

Study limitations included the observational nature, lack of information on pain duration and severity that could lead to confounding, and potential underestimation of effect sizes due to misclassification of exposures.

This article originally appeared on Psychiatry Advisor