Systematic Review and Meta‐Analysis on Neuropsychological Effects of Long‐Term Use of Opioids in Patients With Chronic Noncancer Pain

Abstract

Background and Objective Opioid treatments are often prolonged because of the pathology causing pain. We focused on the cognitive functions in patients with chronic pain treated with opioids. This topic is currently controversial, but in practice, the consequences are important in patients’ daily lives, social interactions, working ability, and driving. Database and Data Treatment Medline and Embase databases were searched for eligible articles. We included studies that enrolled patients with chronic noncancer pain, studies with patients receiving opioid treatment, studies with a control group not using opioids, and studies in which cognitive functions were evaluated with specific tests. The cognitive areas examined were as follows: attention, reaction time, executive functions, psychomotor speed, memory, and working memory. From 356 abstracts screened, 9 articles satisfied eligibility criteria and were included in our review: 7 observational and 7 experimental studies. We classified the pain treatments as follows: opioids, other drugs active on the central nervous system (CNS) (antidepressants/anticonvulsants), and treatments not specifically targeted to the CNS. Results Statistically significant differences were seen only with regard to attention between opioids alone and no centrally acting treatment (standardized mean difference [SMD]: −0.53, 95% confidence interval [CI] : −0.91, −0.15; P = 0.007; I2 = 23%) and between opioids combined with antidepressants and/or anticonvulsants and no centrally acting treatment (SMD: −0.62, 95% CI: −1.04, −0.20; P = 0.004; I2 = 0%). No other significant differences were observed. Conclusions Opioids reduce attention when compared with treatments not targeted on the CNS. If opioids are used together with antidepressants and/or anticonvulsants, this effect increases. Significance These findings on the neuropsychological effects of opioids could be used to generate strategies to refine pain treatments.

The Effects of Opioids on Cognition in Older Adults With Cancer and Chronic Noncancer Pain: A Systematic Review

“…Additionally, systematic identification and assessment of cognitive impairment could be useful in guiding opioid therapy. However, there is little consensus on which tools and assessments are effective in identifying cognitive impairment and which cognitive domains are impacted by opioids (34,43,44).…”

European clinical practice recommendations on opioids for chronic noncancer pain – Part 2: Special situations*

“…Comment: A systematic review of case-control studies on neuropsychological effects of LTOT for CNCP found that opioids reduce attention when compared with treatments not targeted on the CNS. If opioids are used together with antidepressants and/or anticonvulsants, this effect increases (Allegri et al, 2019).…”

<p>Cognitive Function During Opioid Tapering in Patients with Chronic Pain: A Prospective Cohort Study</p>

“…14 Consequently, tapering of opioids has been encouraged in recent guidelines, including the American Centers for Disease Control and the Canadian National Pain Centre. 1,15 Studies on cognitive function during opioid therapy have presented conflicting results, with some suggesting improved cognitive function, [16][17][18] some worsened function, [19][20][21][22][23] and some suggesting no impact. [24][25][26][27][28][29] A recent review found only significantly reduced attention among opioid users compared to non-users, but most included studies were cross-sectional and used different neuropsychological tests, thus limiting proper data synthesis into meta-analyses.…”

“…[24][25][26][27][28][29] A recent review found only significantly reduced attention among opioid users compared to non-users, but most included studies were cross-sectional and used different neuropsychological tests, thus limiting proper data synthesis into meta-analyses. 23 Methodological flaws in previous, mostly observational studies, have hindered differentiation of cognitive dysfunction caused by the chronic pain condition and possible cognitive effects of long-term opioid therapy. 30 The majority of published studies have examined the cognitive function during opioid dose escalation, [16][17][18][24][25][26] though the current trend is towards tapering off opioids.…”