Opioids for chronic noncancer pain: a meta-analysis of effectiveness and side effects

An enriched enrollment randomized withdrawal (EERW) trial design has been advocated to be useful for the study of drugs that are beneficial to only a fraction of the individuals who take them. Some investigators defend the use of enrichment designs for opioids in chronic noncancer pain (CNCP), reasoning that opioids may appear to underperform in clinically heterogeneous contexts, ie, that substantial efficacy in a particular patient subgroup may be diluted or masked by poor efficacy in another subgroup. The authors previously published a systematic review of opioids for CNCP in 2006; however, at that time, there were only a few EERW trials available for comparison. This more exhaustive, updated review compares the results between EERW and non-EERW trials of opioids for a variety of CNCP conditions.BACKGROUND: An enriched enrollment randomized withdrawal (EERW) design excludes potential participants who are nonresponders or who cannot tolerate the experimental drug before random assignment. It is unclear whether EERW design has an influence on the efficacy and safety of opioids for chronic noncancer pain (CNCP).OBJECTIVES: The primary objective was to compare the results from EERW and non-EERW trials of opioids for CNCP. Secondary objectives were to compare weak versus strong opioids, subgroups of patients with different types of pain, and the efficacy of opiods compared with placebo versus other drugs.METHODS: MEDLINE, EMBASE and CENTRAL were searched up to July 2009, for randomized controlled trials of any opioid for CNCP. Meta-analyses and meta-regressions were conducted to compare the results. Treatment efficacy was assessed by effect sizes (small, medium and large) and the incidence of adverse effects was assessed by a clinically relevant mean difference of 10% or greater.RESULTS: Sixty-two randomized trials were included. In 61 trials, the duration was less than 16 weeks. There was no difference in efficacy between EERW and non-EERW trials for both pain (P=0.6) and function (P=0.3). However, EERW trials failed to detect a clinically relevant difference for nausea, vomiting, somnolence, dizziness and dry skin/itching compared with non-EERW. Opioids were more effective than placebo in patients with nociceptive pain (effect size=0.60, 95% CI 0.49 to 0.72) and neuropathic pain (effect size=0.56, 95% CI 0.38 to 0.73).CONCLUSION: EERW trial designs appear not to bias the results of efficacy, but they underestimate the adverse effects. The present updated meta-analysis shows that weak and strong opioids are effective for CNCP of both nociceptive and neuropathic origin.

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How Can We Best Reduce Pain Catastrophizing in Adults With Chronic Noncancer Pain? A Systematic Review and Meta-Analysis

Journal of Pain ◽

10.1016/j.jpain.2017.09.010 ◽

2018 ◽

Vol 19 (3) ◽

pp. 233-256 ◽

Cited By ~ 39

Author(s):

Robert Schütze ◽

Clare Rees ◽

Anne Smith ◽

Helen Slater ◽

Jared M. Campbell ◽

...

Keyword(s):

Systematic Review ◽

Pain Catastrophizing ◽

Meta Analysis ◽

Chronic Noncancer Pain ◽

Noncancer Pain

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Faculty Opinions recommendation of Cannabis and cannabinoids for the treatment of people with chronic noncancer pain conditions: a systematic review and meta-analysis of controlled and observational studies.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.733321840.793551729 ◽

2018 ◽

Author(s):

Stephan Schug

Keyword(s):

Systematic Review ◽

Observational Studies ◽

Meta Analysis ◽

Chronic Noncancer Pain ◽

Noncancer Pain

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Trigger Point Manual Therapy for the Treatment of Chronic Noncancer Pain in Adults: A Systematic Review and Meta-analysis

Archives of Physical Medicine and Rehabilitation ◽

10.1016/j.apmr.2018.06.019 ◽

2019 ◽

Vol 100 (3) ◽

pp. 562-577 ◽

Cited By ~ 3

Author(s):

Diarmuid Denneny ◽

Helena C. Frawley ◽

Katrine Petersen ◽

Rebecca McLoughlin ◽

Suzanne Brook ◽

...

Keyword(s):

Systematic Review ◽

Manual Therapy ◽

Trigger Point ◽

Meta Analysis ◽

Chronic Noncancer Pain ◽

Noncancer Pain

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The prevalence and economic impact of prescription opioid-related side effects among patients with chronic noncancer pain

Journal of Opioid Management ◽

10.5055/jom.2013.0165 ◽

2013 ◽

Vol 9 (4) ◽

pp. 239-254 ◽

Cited By ~ 15

Author(s):

Jasmina I. Ivanova, MA ◽

Howard G. Birnbaum, PhD ◽

Yana Yushkina, BA ◽

Rachael A. Sorg, MPH ◽

John Reed, MD ◽

...

Keyword(s):

Side Effects ◽

Side Effect ◽

Healthcare Costs ◽

Claims Data ◽

Patient Survey ◽

Prescription Opioid ◽

Chronic Noncancer Pain ◽

Medical Group Practice ◽

Outcomes Measures ◽

Noncancer Pain

Objectives: To estimate the prevalence of opioid-related side effects among patients with chronic noncancer pain (CNCP) who initiated opioids and compare healthcare costs of patients with and without side effects using patient survey, medical charts, and claims data.Patients, participants: Patients initiating opioids, who were aged ≥18 years, had ≥1 pain diagnosis, and did not have cancer, were identified through claims data and medical records from a Central Massachusetts medical group practice and mailed surveys between October 2010 and July 2012.Main outcomes measures: Prevalence of opioid-related side effects was estimated from patient surveys, charts, and claims data within 90 days after opioid initiation (study period). Study period healthcare costs were compared between patients with and without side effects (self-reported problematic side effects or side effects recorded in medical charts or claims).Results: Among patients with CNCP who initiated opioids and completed the survey (N = 167), the average age was 53 years, and 62.9 percent were women. Based on the survey, charts, and claims, 91.6 percent, 15.0 percent, and 19.2 percent of patients, respectively, had ≥1 opioid-related side effect. Overall, 59.3 percent of patients reported having ≥1 problematic side effect or side effect recorded in charts or claims. In the analysis that controlled for baseline characteristics and resource use, patients with versus without side effects had higher mean study period healthcare costs ($3,347 vs $2,521, p = 0.049).Conclusions: Prevalence of opioid-related side effects among patients with CNCP who initiated opioids was substantially higher based on patient survey than from charts or claims. Opioid-related side effects were associated with significantly higher healthcare costs.

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