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BMJ (Clinical Research Ed.) Oct 2021To assess the effectiveness and safety of different preparations and doses of non-steroidal anti-inflammatory drugs (NSAIDs), opioids, and paracetamol for knee and hip...
OBJECTIVE
To assess the effectiveness and safety of different preparations and doses of non-steroidal anti-inflammatory drugs (NSAIDs), opioids, and paracetamol for knee and hip osteoarthritis pain and physical function to enable effective and safe use of these drugs at their lowest possible dose.
DESIGN
Systematic review and network meta-analysis of randomised trials.
DATA SOURCES
Cochrane Central Register of Controlled Trials (CENTRAL), Medline, Embase, regulatory agency websites, and ClinicalTrials.gov from inception to 28 June 2021.
ELIGIBILITY CRITERIA FOR SELECTING STUDIES
Randomised trials published in English with ≥100 patients per group that evaluated NSAIDs, opioids, or paracetamol (acetaminophen) to treat osteoarthritis.
OUTCOMES AND MEASURES
The prespecified primary outcome was pain. Physical function and safety outcomes were also assessed.
REVIEW METHODS
Two reviewers independently extracted outcomes data and evaluated the risk of bias of included trials. Bayesian random effects models were used for network meta-analysis of all analyses. Effect estimates are comparisons between active treatments and oral placebo.
RESULTS
192 trials comprising 102 829 participants examined 90 different active preparations or doses (68 for NSAIDs, 19 for opioids, and three for paracetamol). Five oral preparations (diclofenac 150 mg/day, etoricoxib 60 and 90 mg/day, and rofecoxib 25 and 50 mg/day) had ≥99% probability of more pronounced treatment effects than the minimal clinically relevant reduction in pain. Topical diclofenac (70-81 and 140-160 mg/day) had ≥92.3% probability, and all opioids had ≤53% probability of more pronounced treatment effects than the minimal clinically relevant reduction in pain. 18.5%, 0%, and 83.3% of the oral NSAIDs, topical NSAIDs, and opioids, respectively, had an increased risk of dropouts due to adverse events. 29.8%, 0%, and 89.5% of oral NSAIDs, topical NSAIDs, and opioids, respectively, had an increased risk of any adverse event. Oxymorphone 80 mg/day had the highest risk of dropouts due to adverse events (51%) and any adverse event (88%).
CONCLUSIONS
Etoricoxib 60 mg/day and diclofenac 150 mg/day seem to be the most effective oral NSAIDs for pain and function in patients with osteoarthritis. However, these treatments are probably not appropriate for patients with comorbidities or for long term use because of the slight increase in the risk of adverse events. Additionally, an increased risk of dropping out due to adverse events was found for diclofenac 150 mg/day. Topical diclofenac 70-81 mg/day seems to be effective and generally safer because of reduced systemic exposure and lower dose, and should be considered as first line pharmacological treatment for knee osteoarthritis. The clinical benefit of opioid treatment, regardless of preparation or dose, does not outweigh the harm it might cause in patients with osteoarthritis.
SYSTEMATIC REVIEW REGISTRATION
PROSPERO number CRD42020213656.
Topics: Acetaminophen; Administration, Oral; Administration, Topical; Aged; Analgesics, Opioid; Anti-Inflammatory Agents, Non-Steroidal; Female; Humans; Male; Middle Aged; Minimal Clinically Important Difference; Network Meta-Analysis; Osteoarthritis, Hip; Osteoarthritis, Knee; Pain Management
PubMed: 34642179
DOI: 10.1136/bmj.n2321 -
Journal of Pain and Symptom Management Feb 2010Opioids are recommended for control of moderate-to-severe, chronic, malignant, and nonmalignant pain. A controlled-release formulation of the opioid oxymorphone has... (Meta-Analysis)
Meta-Analysis Review
Opioids are recommended for control of moderate-to-severe, chronic, malignant, and nonmalignant pain. A controlled-release formulation of the opioid oxymorphone has recently been launched. The aim of this review was to assess the effectiveness of oxymorphone as an analgesic in chronic pain. A systematic search for published studies of oral oxymorphone in the management of chronic pain was conducted. The studies were evaluated for their internal validity according to standard criteria. They were also evaluated for their external validity and research ethic aspects. A meta-analysis was performed to examine the effect of oxymorphone compared with placebo. Nine studies were evaluated; three were excluded because of low quality. Six controlled studies (duration 2-12 weeks) included a total of 1489 subjects suffering from chronic low back pain, chronic pain from osteoarthritis, and chronic cancer pain. Three of the studies were of high quality and three of medium quality. External validity was assessed to be high, medium, and low (in one, three, and two studies, respectively). The meta-analysis suggests that daily doses of 40-100mg are superior to placebo; however, the estimate (reduction of pain intensity compared with placebo) of the treatment effect is imprecise (95% confidence interval -17.08, -8.69). Limited evidence suggests that oxymorphone is effective for pain control in patients with cancer. No significant differences between oxymorphone and oxycodone at equipotent doses were found. In conclusion, oxymorphone is superior to placebo. There is no evidence that the efficacy of oxymorphone differs from other opioids.
Topics: Analgesics, Opioid; Chronic Disease; Humans; Low Back Pain; Neoplasms; Osteoarthritis; Oxymorphone; Pain; Randomized Controlled Trials as Topic
PubMed: 20152592
DOI: 10.1016/j.jpainsymman.2009.07.010 -
The Cochrane Database of Systematic... Oct 2017Chronic pain is common and can be challenging to manage. Despite increased utilisation of opioids, the safety and efficacy of long-term use of these compounds for... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Chronic pain is common and can be challenging to manage. Despite increased utilisation of opioids, the safety and efficacy of long-term use of these compounds for chronic non-cancer pain (CNCP) remains controversial. This overview of Cochrane Reviews complements the overview entitled 'High-dose opioids for chronic non-cancer pain: an overview of Cochrane Reviews'.
OBJECTIVES
To provide an overview of the occurrence and nature of adverse events associated with any opioid agent (any dose, frequency, or route of administration) used on a medium- or long-term basis for the treatment of CNCP in adults.
METHODS
We searched the Cochrane Database of Systematic Reviews (the Cochrane Library) Issue 3, 2017 on 8 March 2017 to identify all Cochrane Reviews of studies of medium- or long-term opioid use (2 weeks or more) for CNCP in adults aged 18 and over. We assessed the quality of the reviews using the AMSTAR criteria (Assessing the Methodological Quality of Systematic Reviews) as adapted for Cochrane Overviews. We assessed the quality of the evidence for the outcomes using the GRADE framework.
MAIN RESULTS
We included a total of 16 reviews in our overview, of which 14 presented unique quantitative data. These 14 Cochrane Reviews investigated 14 different opioid agents that were administered for time periods of two weeks or longer. The longest study was 13 months in duration, with most in the 6- to 16-week range. The quality of the included reviews was high using AMSTAR criteria, with 11 reviews meeting all 10 criteria, and 5 of the reviews meeting 9 out of 10, not scoring a point for either duplicate study selection and data extraction, or searching for articles irrespective of language and publication type. The quality of the evidence for the generic adverse event outcomes according to GRADE ranged from very low to moderate, with risk of bias and imprecision being identified for the following generic adverse event outcomes: any adverse event, any serious adverse event, and withdrawals due to adverse events. A GRADE assessment of the quality of the evidence for specific adverse events led to a downgrading to very low- to moderate-quality evidence due to risk of bias, indirectness, and imprecision.We calculated the equivalent milligrams of morphine per 24 hours for each opioid studied (buprenorphine, codeine, dextropropoxyphene, dihydrocodeine, fentanyl, hydromorphone, levorphanol, methadone, morphine, oxycodone, oxymorphone, tapentadol, tilidine, and tramadol). In the 14 Cochrane Reviews providing unique quantitative data, there were 61 studies with a total of 18,679 randomised participants; 12 of these studies had a cross-over design with two to four arms and a total of 796 participants. Based on the 14 selected Cochrane Reviews, there was a significantly increased risk of experiencing any adverse event with opioids compared to placebo (risk ratio (RR) 1.42, 95% confidence interval (CI) 1.22 to 1.66) as well as with opioids compared to a non-opioid active pharmacological comparator, with a similar risk ratio (RR 1.21, 95% CI 1.10 to 1.33). There was also a significantly increased risk of experiencing a serious adverse event with opioids compared to placebo (RR 2.75, 95% CI 2.06 to 3.67). Furthermore, we found significantly increased risk ratios with opioids compared to placebo for a number of specific adverse events: constipation, dizziness, drowsiness, fatigue, hot flushes, increased sweating, nausea, pruritus, and vomiting.There was no data on any of the following prespecified adverse events of interest in any of the included reviews in this overview of Cochrane Reviews: addiction, cognitive dysfunction, depressive symptoms or mood disturbances, hypogonadism or other endocrine dysfunction, respiratory depression, sexual dysfunction, and sleep apnoea or sleep-disordered breathing. We found no data for adverse events analysed by sex or ethnicity.
AUTHORS' CONCLUSIONS
A number of adverse events, including serious adverse events, are associated with the medium- and long-term use of opioids for CNCP. The absolute event rate for any adverse event with opioids in trials using a placebo as comparison was 78%, with an absolute event rate of 7.5% for any serious adverse event. Based on the adverse events identified, clinically relevant benefit would need to be clearly demonstrated before long-term use could be considered in people with CNCP in clinical practice. A number of adverse events that we would have expected to occur with opioid use were not reported in the included Cochrane Reviews. Going forward, we recommend more rigorous identification and reporting of all adverse events in randomised controlled trials and systematic reviews on opioid therapy. The absence of data for many adverse events represents a serious limitation of the evidence on opioids. We also recommend extending study follow-up, as a latency of onset may exist for some adverse events.
Topics: Adult; Analgesics, Opioid; Chronic Pain; Humans; Patient Dropouts; Randomized Controlled Trials as Topic; Review Literature as Topic; Time Factors
PubMed: 29084357
DOI: 10.1002/14651858.CD012509.pub2 -
Experimental Biology and Medicine... Nov 2023The opioid epidemic has become a serious national crisis in the United States. An indepth systematic analysis of opioid-related adverse events (AEs) can clarify the...
The opioid epidemic has become a serious national crisis in the United States. An indepth systematic analysis of opioid-related adverse events (AEs) can clarify the risks presented by opioid exposure, as well as the individual risk profiles of specific opioid drugs and the potential relationships among the opioids. In this study, 92 opioids were identified from the list of all Food and Drug Administration (FDA)-approved drugs, annotated by RxNorm and were classified into 13 opioid groups: buprenorphine, codeine, dihydrocodeine, fentanyl, hydrocodone, hydromorphone, meperidine, methadone, morphine, oxycodone, oxymorphone, tapentadol, and tramadol. A total of 14,970,399 AE reports were retrieved and downloaded from the FDA Adverse Events Reporting System (FAERS) from 2004, Quarter 1 to 2020, Quarter 3. After data processing, Empirical Bayes Geometric Mean (EBGM) was then applied which identified 3317 pairs of potential risk signals within the 13 opioid groups. Based on these potential safety signals, a comparative analysis was pursued to provide a global overview of opioid-related AEs for all 13 groups of FDA-approved prescription opioids. The top 10 most reported AEs for each opioid class were then presented. Both network analysis and hierarchical clustering analysis were conducted to further explore the relationship between opioids. Results from the network analysis revealed a close association among fentanyl, oxycodone, hydrocodone, and hydromorphone, which shared more than 22 AEs. In addition, much less commonly reported AEs were shared among dihydrocodeine, meperidine, oxymorphone, and tapentadol. On the contrary, the hierarchical clustering analysis further categorized the 13 opioid classes into two groups by comparing the full profiles of presence/absence of AEs. The results of network analysis and hierarchical clustering analysis were not only consistent and cross-validated each other but also provided a better and deeper understanding of the associations and relationships between the 13 opioid groups with respect to their adverse effect profiles.
Topics: Analgesics, Opioid; Bayes Theorem; Data Mining; Fentanyl; Hydrocodone; Hydromorphone; Meperidine; Oxycodone; Oxymorphone; Tapentadol; United States
PubMed: 38158803
DOI: 10.1177/15353702231211860 -
Pain Physician May 2016Opioid overdose continues to be a significant and growing cause of preventable mortality and morbidity. Studies suggest that unintentional, non-fatal overdose from... (Review)
Review
BACKGROUND
Opioid overdose continues to be a significant and growing cause of preventable mortality and morbidity. Studies suggest that unintentional, non-fatal overdose from prescription opioid analgesics constitutes a large portion of total overdose events. The societal burden associated with these events is a frequently overlooked public health concern.
OBJECTIVES
To evaluate unintentional, non-fatal prescription opioid overdoses, including the identification of risk factors, societal burden, and knowledge gaps where further study is warranted.
STUDY DESIGN
Systematic review of the literature for unintentional, non-fatal opioid overdose.
METHODS
Preferred reporting items for systematic reviews and meta-analyses guidelines were used in constructing this systematic review. To determine the scope of the existing literature, a systematic search was conducted using the MEDLINE, CINAHL, PsycINFO, and Web of Science databases.
RESULTS
This systematic review analyzes 24 articles (21 retrospective descriptive analyses, 2 prospective analyses, one phase III trial, and one meta-analysis). Articles were reviewed by authors and relevant data examined. Results show that opioid overdose morbidity is significantly more prevalent than mortality and sequelae of non-fatal events should be studied in more detail.
LIMITATIONS
The limitations of this systematic review include the range of study populations and opioids discussed and the broad and variable definitions of "opioid overdose" in the literature.
CONCLUSIONS
Opioid overdose morbidity and mortality is seen across the entire spectrum of inpatient and outpatient use with significant numbers of adverse events occurring in population segments not identified by high risk indicators. Increased physician awareness and a multi-modal approach could help mitigate the overdose epidemic while maintaining effective pain control for patients.
KEY WORDS
Prescription, opioid, accidental drug overdose, unintentional overdose, drug poisoning, fentanyl, oxycodone, hydrocodone, methadone, oxymorphone, hydromorphone.
Topics: Analgesics, Opioid; Drug Overdose; Humans; Prescription Drug Overuse
PubMed: 27228510
DOI: No ID Found -
The Cochrane Database of Systematic... May 2015Agitation is a common experience for people living with dementia, particularly as day-to-day function and cognition start to decline more. At the present time there are... (Review)
Review
BACKGROUND
Agitation is a common experience for people living with dementia, particularly as day-to-day function and cognition start to decline more. At the present time there are limited pharmacological options for relieving agitation and little is known about the safety and efficacy of opioid drugs in this setting.
OBJECTIVES
To determine the clinical efficacy and safety of opioids for agitation in people with dementia.
SEARCH METHODS
We searched ALOIS, the Cochrane Dementia and Cognitive Improvement Group Specialized Register, on 13 June 2014 using the terms: narcotic OR opioid OR opium OR morphine OR buprenorphine OR codeine OR dextromoramide OR diphenoxylate OR dipipanone OR dextropropoxyphene OR propoxyphene OR diamorphine OR dihydrocodeine OR alfentanil OR fentanyl OR remifentanil OR meptazinol OR methadone OR nalbuphine OR oxycodone OR papaveretum OR pentazocine OR meperidine OR pethidine OR phenazocine OR hydrocodone OR hydromorphone OR levorphanol OR oxymorphone OR butorphanol OR dezocine OR sufentanil OR ketobemidone.ALOIS contains records of clinical trials identified from monthly searches of a number of major healthcare databases such as MEDLINE, EMBASE and PscyINFO, as well as numerous trial registries and grey literature sources.
SELECTION CRITERIA
Randomised, controlled trials of opioids compared to placebo for agitation in people with dementia.
DATA COLLECTION AND ANALYSIS
Two authors independently assessed the studies identified by the search against the inclusion criteria.
MAIN RESULTS
There are currently no completed randomised, placebo controlled trials of opioids for agitation in dementia. There are two potentially relevant trials still in progress.
AUTHORS' CONCLUSIONS
We found insufficient evidence to establish the clinical efficacy and safety of opioids for agitation in people with dementia. There remains a lack of data to determine if or when opioids either relieve or exacerbate agitation. More evidence is needed to guide the effective, appropriate and safe use of opioids in dementia.
Topics: Analgesics, Opioid; Dementia; Humans; Psychomotor Agitation
PubMed: 25972091
DOI: 10.1002/14651858.CD009705.pub2 -
Current Medical Research and Opinion Jul 2011For chronic pain treatment many health care authorities consider morphine to be the reference standard for strategic decisions in pain therapy. Although morphine's... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
For chronic pain treatment many health care authorities consider morphine to be the reference standard for strategic decisions in pain therapy. Although morphine's effectiveness is clear and its cost is low, it's unclear whether morphine should remain the first choice or reference treatment.
RESEARCH DESIGN AND METHODS
We performed a systematic review to evaluate the evidence available to support the position of morphine as the reference standard for step III opioids based on efficacy and tolerability outcomes.
RESULTS
The search yielded 5,675 titles and 56 studies were included. Considerable heterogeneity precluded pair-wise meta-analysis on change of pain intensity and no difference between morphine and other opioids were found for tolerability outcomes. The network meta-analysis showed no statistically significant difference in change of pain intensity between morphine and oxycodone, methadone and oxymorphone. Compared to morphine, patients using buprenorphine are more likely to discontinue treatment due to lack of effect (OR 2.32, 95% CI 1.37 to 3.95). Patients using methadone are more likely to discontinue due to adverse events (OR 3.09, 95% CI 1.14 to 8.36), whereas this risk is decreased for patients using fentanyl (OR 0.29, 95% CI 0.17 to 0.50) or buprenorphine (OR 0.30, 95% CI 0.16 to 0.53). The most important limitation of this review is that the included studies are heterogeneous with regard to study population and intervention, which may affect the pooled effect estimates. The main strength is that we only included parallel RCTs, the strongest design for intervention studies.
CONCLUSIONS
The current evidence is moderate, both in respect to the number of directly comparative studies and in the quality of reporting of these studies. No clear superiority in efficacy and tolerability of morphine over other opioids was found in pair-wise and network analyses. Based on these results, a justification for the placement of morphine as the reference standard for the treatment of severe chronic pain cannot be supported.
Topics: Adult; Analgesics, Opioid; Chronic Disease; Data Interpretation, Statistical; Humans; Matched-Pair Analysis; Morphine; Pain; Randomized Controlled Trials as Topic; Standard of Care; Treatment Outcome
PubMed: 21635191
DOI: 10.1185/03007995.2011.586332 -
Schmerz (Berlin, Germany) Feb 2015The efficacy, tolerability and safety of opioid therapy in chronic osteoarthritis (OA) pain is under debate. We updated a Cochrane systematic review on the efficacy and... (Comparative Study)
Comparative Study Review
[Opioids in chronic osteoarthritis pain. A systematic review and meta-analysis of efficacy, tolerability and safety in randomized placebo-controlled studies of at least 4 weeks duration].
BACKGROUND
The efficacy, tolerability and safety of opioid therapy in chronic osteoarthritis (OA) pain is under debate. We updated a Cochrane systematic review on the efficacy and safety of opioids in chronic OA pain published in 2009.
METHODS
We screened MEDLINE, Scopus and the Cochrane Central Register of Controlled Trials (CENTRAL) up until October 2013, as well as reference sections of original studies and systematic reviews of randomized controlled trials (RCTs) of opioids in chronic osteoarthritis (OA) pain. We included double-blind randomized placebo-controlled studies lasting ≥ 4 weeks. Using a random effects model, absolute risk differences (RD) were calculated for categorical data and standardized mean differences (SMD) for continuous variables.
RESULTS
We included 20 RCTs with 33 treatment arms and 8545 participants. Median study duration was 12 (4-24) weeks. Oxycodone and tramadol were each tested in six studies; buprenorphine, hydromorphone, morphine and tapentadol each in two studies and codeine, fentanyl and oxymorphone in one study each. Results are reported with 95 % confidence intervals (CIs). Opioids were superior to placebo in reducing pain intensity (SMD - 0.22 [- 0.28, - 0.17], p < 0.00001; 16 studies with 6743 participants). Opioids were not superior to placebo in 50 % pain reduction (RD - 0.00 [- 0.07, 0.07], p = 0.96; two studies with 2684 participants). Opioids were superior to placebo in terms of reports of much or very much global improvement (RD 0.13 [0.05, 0.21], p = 0.002; three studies with 2251 participants). Opioids were superior to placebo in improving physical functioning (SMD - 0.22 [- 0.28, - 0.17], p < 0.00001; 14 studies with 5887 participants). Patients dropped out more frequently with opioids than with placebo (RD 0.17 [0.14, 0.21], p < 0.00001; 15 studies with 6834 participants; number needed to harm 5 [4-6]. There was no significant difference between opioids and placebo in the frequency of serious adverse events (SAE) or deaths over the respective observation periods.
CONCLUSION
Opioids were superior to placebo in terms of efficacy and inferior in terms of tolerability. The effect sizes of average reduction in pain intensity and physical disability were small. Opioids and placebo did not differ in terms of safety. The conclusion on the safety of opioids compared to placebo is limited by the low number of SAE and deaths. Short-term opioid therapy may be considered in selected chronic OA pain patients. No current evidence-based guideline recommends opioids as first-line treatment option for chronic OA pain. To provide superior evidence for future treatment guidelines, RCTs must directly compare existing pharmacological and nonpharmacological therapies and administer these in various combinations and sequences. The English full-text version of this article is freely available at SpringerLink (under "Supplemental").
Topics: Adult; Analgesics, Opioid; Chronic Pain; Double-Blind Method; Evidence-Based Medicine; Humans; Long-Term Care; Osteoarthritis; Pain Measurement; Randomized Controlled Trials as Topic; Treatment Outcome
PubMed: 25376547
DOI: 10.1007/s00482-014-1451-1 -
Current Medical Research and Opinion Oct 2011A systematic review of chronic pain treatment with strong opioids (step 3 WHO pain ladder) and a comparison to a new drug recently approved for the treatment of severe... (Comparative Study)
Comparative Study Review
AIM
A systematic review of chronic pain treatment with strong opioids (step 3 WHO pain ladder) and a comparison to a new drug recently approved for the treatment of severe chronic pain in Europe, tapentadol (Palexia, Nucynta*), were performed.
METHODS
Thirteen electronic databases were searched as well as a number of other sources from 1980 up to November 2010 for relevant randomized controlled clinical trials in chronic moderate and severe pain investigating at least one step 3 opioid. Chronic pain could be nociceptive or neuropathic, malignant or non-malignant, all systemic administrations were considered as well as trials of different lengths. Two separate analyses were performed, one only for trials which reported (at least as sub-groups) the outcome in patients with severe pain, the other including both moderate and severe pain conditions. With the exception of the direct comparison between tapentadol, oxycodone and placebo, indirect comparisons were performed based on a network analysis. Trials with an enriched or an enriched withdrawal design were excluded. Primary (pain intensity) and a number of secondary endpoints were evaluated, including pain relief (30% and 50%), patient global impression of change, quality of life, quality of sleep, discontinuations, as well as serious adverse events and selected adverse events.
RESULTS
Only 10 trials were eligible for analysis of patients with severe pain (eight investigating tapentadol and two trials comparing buprenorphine patch vs placebo). For moderate and severe pain, 42 relevant trials were identified and indirect comparisons with transdermal buprenorphine, transdermal fentanyl, hydromorphone, morphine, and oxymorphone were performed. This report focuses on the network analysis. Tapentadol showed statistically favourable results over oxycodone for pain intensity, 30% and 50% pain relief, patient global impression of change (PGIC), and quality of life. Furthermore, some of the most important adverse events of chronic opioid treatment were significantly less frequent with tapentadol as compared to oxycodone, i.e. constipation, nausea, and vomiting; discontinuations due to these adverse events were found significantly reduced with tapentadol. Similar results were obtained for the network analysis, i.e. tapentadol was superior for the primary outcome (pain intensity) to hydromorphone and morphine, whereas fentanyl and oxymorphone showed trends in favour of these treatments. Significantly less frequent gastrointestinal adverse events of tapentadol were observed in comparison with fentanyl, hydromorphone, morphine, and oxymorphone, apparently leading to significantly reduced treatment discontinuations (for any reason).
CONCLUSIONS
Taken together, the benefit-risk ratio of tapentadol appears to be improved compared to step 3 opioids.
Topics: Chronic Pain; Clinical Trials as Topic; Databases, Factual; Europe; Humans; Pain Measurement; Phenols; Quality of Life; Tapentadol
PubMed: 21905968
DOI: 10.1185/03007995.2011.611494 -
Schmerz (Berlin, Germany) Feb 2015The efficacy and safety of opioid therapy in chronic low back pain (CLBP) is under debate. We updated a recent systematic review on the efficacy and safety of opioids in... (Comparative Study)
Comparative Study Meta-Analysis Review
[Opioids in chronic low back pain. A systematic review and meta-analysis of efficacy, tolerability and safety in randomized placebo-controlled studies of at least 4 weeks duration].
BACKGROUND
The efficacy and safety of opioid therapy in chronic low back pain (CLBP) is under debate. We updated a recent systematic review on the efficacy and safety of opioids in CLBP.
METHODS
We screened MEDLINE, Scopus and the Cochrane Central Register of Controlled Trials (CENTRAL) up until October 2013, as well as reference sections of original studies and systematic reviews of randomized controlled trials (RCTs) of opioids in CLBP. We included double-blind randomized placebo-controlled studies of at least 4 weeks duration. Using a random effects model, absolute risk differences (RD) were calculated for categorical data and standardized mean differences (SMD) for continuous variables.
RESULTS
We included 12 RCTs with 17 treatment arms and 4375 participants. Median study duration was 12 (4-16) weeks. Of the 17 treatment arms, seven (41.2 %) used oxycodone; four (23.6 %) tramadol; buprenorphine and oxymorphone were each used in two (11.8 %) and hydromorphone and tapentadol each in one (5.8 %). The results for studies with parallel/cross-over design were as follows (with 95 % confidence interval, CI): opioids were superior to placebo in reducing pain intensity (SMD - 0.29 [- 0.37, - 0.21], p < 0.0001; six studies with 2896 participants). Opioids were superior to placebo in 50 % pain reduction (RD 0.05 [0.01, 0.10], p = 0.01; two studies with 1492 participants; number needed to benefit (NNTB) 19 [95 % CI 10-107]). Opioids were not superior to placebo in reports of much or very much improved pain (RD 0.16 [- 0.01, 0.34], p = 0.07; two studies with 1153 participants). Opioids were superior to placebo in improving physical functioning (SMD - 0.22 [- 0.31, - 0.12], p < 0.0001; four studies with 1895 participants). Patients dropped out less frequently with opioids than with placebo due to lack of efficacy (RD - 0.10 [- 0.16, - 0.04], p = 0.001; five studies with 3168 participants; NNTB 10 [8-13]). Patients dropped out more frequently with opioids than with placebo due to adverse events (RD 0.12 [0.05, 0.19], p = 0.0007; six studies with 2910 participants; number needed to harm (NNTH) 7 [95 % CI 6-8]). There was no significant difference between opioids and placebo in terms of the frequency of serious adverse events or deaths.
CONCLUSION
Opioids were superior to placebo in terms of efficacy and inferior in terms of tolerability. Opioids and placebo did not differ in terms of safety during the study period. The conclusion on the safety of opioids compared to placebo is limited by the low number of serious adverse events and deaths. Short-term and intermediate-term opioid therapy may be considered in selected CLBP patients. The English full-text version of this article is freely available at SpringerLink (under "Supplemental").
Topics: Activities of Daily Living; Analgesics, Opioid; Cross-Over Studies; Humans; Long-Term Care; Low Back Pain; Pain Measurement; Randomized Controlled Trials as Topic; Treatment Outcome
PubMed: 25503883
DOI: 10.1007/s00482-014-1449-8