Opioids and Neurocognitive Symptoms: Monitoring Key During Long-Term Therapy

Patients receiving long-term opioid therapy are more likely to experience neurocognitive symptoms during the course of treatment than in the period prior to treatment initiation or after discontinuation, according to study results published in the Clinical Journal of Pain.

To evaluate the incidence and risk factors of opioid-related neurocognitive symptoms in patients receiving long-term opioid therapy, researchers conducted a retrospective cohort study using electronic health record data from the Veterans Health Administration. Adult patients who initiated at least 1 course of long-term opioid therapy from January to December of 2018 and had no opioid exposure within the previous 180 days were included in the study. The researchers assessed patients for neurocognitive symptoms in the 6 months prior to long-term opioid therapy initiation, during therapy, and up to 1 year after discontinuation. Cox proportional hazards regression models were employed for statistical analysis.

Long-term opioid therapy was defined as having an opioid prescription for at least 90 consecutive days. Opioid-related neurocognitive symptoms included cognitive impairment, sedation, light-headedness, altered mental status, and intoxication.

Among 55,652 patients (age range, 18-75 years) included in the final study population, 62.4% were aged 55 to 75 years, 91.7% were men, 69.7% were White, and 69.3% had conditions or disabilities associated with military service. The most commonly reported concurrent mental health diagnoses were major depressive disorder (38.5%), post-traumatic stress disorder (24.2%), and generalized anxiety disorder (20.4%). Additional concurrent diagnoses included diabetes (36.9%), chronic obstructive pulmonary disease (22.9%), cardiovascular disease (17.1%), and chronic kidney disease (12.9%). Nearly all patients (93.2%) received long-term opioid therapy for more than 1 year.

Overall, 1694 (3.0%) patients experienced opioid-related neurocognitive symptoms. The highest incidence was observed during the course of therapy (2.73 per 100 person-years), followed by the period before treatment initiation and after discontinuation (1.43 and 1.42, respectively, per 100 person-years).

The prevalence of opioid-related neurocognitive symptoms was significantly increased in patients aged 55 to 64 years (3.6%; P <.001) relative to all other age groups. Compared with unmarried patients, married patients exhibited significantly lower prevalence (2.9% vs 3.3%; P =.005).

There was a dose-response relationship observed between opioids and neurocognitive symptoms, with higher doses associated with greater symptom prevalence. Moreover, opioid-related neurocognitive symptoms in patients on long-term therapy occurred most frequently within the first 12 months of treatment.

In adjusted analyses, concurrent diagnoses and other factors associated with increased risk for opioid-related neurocognitive symptoms were as follows:

• Asian race (hazard ratio [HR], 2.20; 95% CI, 1.09-4.44; P =.03);
• Cirrhosis (HR, 1.73; 95% CI, 1.34-2.24; P =.01);
• Substance use disorder (HR, 1.62; 95% CI, 1.36-1.92; P =.01);
• Dementia (HR, 1.50; 95% CI, 1.12-2.00; P =.01);
• Traumatic brain injury (HR, 1.42; 95% CI, 1.06-1.91; P =.02)
• Chronic kidney disease (HR, 1.41; 95% CI, 1.19-1.66; P =.01)
• Major depressive disorder (HR, 1.31; 95% CI, 1.14-1.49; P =.01);
• Post-traumatic stress disorder (HR, 1.18; 95% CI, 1.02-1.37; P =.02);
• Cardiovascular disease (HR, 1.18; 95% CI, 1.01-1.37; P =.04); and
• Chronic obstructive pulmonary disease (HR, 1.16; 95% CI, 1.01-1.33; P =.03).

Study limitations include small absolute differences, the lack of data on cancer diagnoses and types of opioids, the use of data captured from electronic health records, and potentially reduced generalizability to the general population.

According to the researchers, “These findings highlight the importance of monitoring NCS [neurocognitive symptoms] in patients on LTOT [long-term opioid therapy] as part of a broader strategy to mitigate opioid-related harms.”

This article originally appeared on Clinical Pain Advisor