Occurrence of Opioid-Related Neurocognitive Symptoms Associated With Long-term Opioid Therapy

Neurocognitive symptoms (NCSs) may be early indicators of opioid-related harm. We aimed to evaluate the incidence and potential attribution of opioid-related NCS among patients on long-term opioid therapy (LOT) by using natural language processing to extract data from the electronic health records within the Veterans Health Administration.

We conducted a retrospective cohort study of patients prescribed LOT in 2018. NCS were identified from clinical notes across 3 periods: 6 months before LOT initiation, during LOT, and 1-year post-LOT discontinuation. Opioid-related NCS included cognitive impairment, sedation, light-headedness, altered mental status, and intoxication. We calculated incidence rates, incidence rate ratios, and hazard ratios to evaluate the occurrence and potential opioid attribution of NCS across these periods.

Among 55,652 patients, 3.1% experienced opioid-related NCS, with the highest incidence observed during LOT. Prevalence of NCS was greater in patients who were: between 55 and 64 (3.6%) or 65 and 74 years old (3.2%), Asian (4.8%, P = 0.02), and had received treatment for substance use disorders (7.1%, P = 0.01). In adjusted proportional hazards models, identified Asian race (hazard ratio: 2.20 [95% CI: 1.09-4.44], P = 0.03), and cooccurring conditions dementia (1.50 [1.12-2.00], 0.01), depression (1.31 [1.14-1.49], <0.01), posttraumatic stress disorder (1.18 [1.02-1.37], 0.02), substance use disorder (1.62 [1.36-1.92], 0.01), cardiovascular disease (1.18 [1.01-1.37], 0.04), chronic obstructive pulmonary disease (1.16 [1.01-1.33], 0.03), cirrhosis (1.73 [1.34-2.24], 0.01), chronic kidney disease (1.41 [1.19, 1.66]; 0.01) and traumatic brain injury (1.42 [1.06-1.91], 0.02) were associated with increased likelihood of NCS. Likelihood of NCS increased with LOT dose and decreased with LOT duration.

This study suggests that opioid-related NCS are most likely to occur during LOT, indicating a potential temporal association with opioid use. These findings highlight the importance of monitoring NCS in patients on LOT as part of a broader strategy to mitigate opioid-related harms.