Occurrence of Opioid Related Neurocognitive Symptoms Associated with long-term Opioid Therapy

Casey León; Minhee L Sung; Joel I Reisman; Weisong Liu; Robert D Kerns; Kirsha S Gordon; Avijit Mitra; Sunjae Kwon; Hong Yu; William C Becker; Wenjun Li

doi:10.1097/AJP.0000000000001266

Occurrence of Opioid Related Neurocognitive Symptoms Associated with long-term Opioid Therapy

Clin J Pain. 2024 Dec 17. doi: 10.1097/AJP.0000000000001266. Online ahead of print.

Authors

Casey León¹, Minhee L Sung^{2

3}, Joel I Reisman⁴, Weisong Liu^{4

5

6}, Robert D Kerns^{2

3

7}, Kirsha S Gordon^{2

8}, Avijit Mitra⁹, Sunjae Kwon⁹, Hong Yu^{4

5

6}, William C Becker^{2

3}, Wenjun Li¹

Affiliations

¹ Department of Public Health and Center for Health Statistics, University of Massachusetts Lowell, Lowell, MA, USA.
² Pain Research, Informatics, Multimorbidities and Education Center, Veterans Affairs Connecticut Healthcare System, West Haven, CT, USA.
³ Program in Addiction Medicine, Department of Internal Medicine, Yale School of Medicine, New Haven, CT, USA.
⁴ Center for Healthcare Organization and Implementation Research, Veterans Affairs Bedford Healthcare System, Bedford, MA, USA.
⁵ Center for Biomedical and Health Research in Data Science, University of Massachusetts Lowell, Lowell, MA, USA.
⁶ Department of Computer Science, University of Massachusetts Lowell, Lowell, MA, USA.
⁷ Department of Psychiatry, Yale School of Medicine, New Haven, CT, USA.
⁸ General Internal Medicine, Department of Internal Medicine, Yale School of Medicine, New Haven, CT, USA.
⁹ College of Information and Computer Sciences, University of Massachusetts Amherst, Amherst, MA, USA.

PMID: 39682036
DOI: 10.1097/AJP.0000000000001266

Abstract

Objective: Neurocognitive symptoms (NCS) 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 (LTOT) by using natural language processing (NLP) to extract data from the electronic health records (EHR) within the Veterans Health Administration.

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

Results: Among 55,652 patients, 3.1% experienced opioid-related NCS, with the highest incidence observed during LTOT. 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 (HR 2.20, 95% CI [1.09-4.44], P=0.03), and co-occurring conditions dementia (1.50 [1.12-2.00], 0.01), depression (1.31 [1.14-1.49], 0.01), post-traumatic 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 LTOT dose and decreased with LTOT duration.

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