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

Nicola Allegri, Simona Mennuni, Eliana Rulli, Nicola Vanacore, Oscar Corli, Irene Floriani, Irene De Simone, Massimo Allegri, Stefano Govoni, Tomaso Vecchi, Giorgio Sandrini, Davide Liccione, Elena Biagioli

Research output: Contribution to journalReview articlepeer-review


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.

Original languageEnglish
Pages (from-to)328-343
Number of pages16
JournalPain Practice
Issue number3
Publication statusPublished - Mar 2019


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