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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 -
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 -
Palliative Medicine Jul 2011Opioid use in patients with renal impairment can lead to increased adverse effects. Opioids differ in their effect in renal impairment in both efficacy and tolerability.... (Review)
Review
A systematic review of the use of opioid medication for those with moderate to severe cancer pain and renal impairment: a European Palliative Care Research Collaborative opioid guidelines project.
BACKGROUND
Opioid use in patients with renal impairment can lead to increased adverse effects. Opioids differ in their effect in renal impairment in both efficacy and tolerability. This systematic literature review forms the basis of guidelines for opioid use in renal impairment and cancer pain as part of the European Palliative Care Research Collaborative's opioid guidelines project.
OBJECTIVE
The objective of this study was to identify and assess the quality of evidence for the safe and effective use of opioids for the relief of cancer pain in patients with renal impairment and to produce guidelines.
SEARCH STRATEGY
The Cochrane Database of Systematic Reviews, Cochrane Central Register of Controlled Trials, MedLine, EMBASE and CINAHL were systematically searched in addition to hand searching of relevant journals.
SELECTION CRITERIA
Studies were included if they reported a clinical outcome relevant to the use of selected opioids in cancer-related pain and renal impairment. The selected opioids were morphine, diamorphine, codeine, dextropropoxyphene, dihydrocodeine, oxycodone, hydromorphone, buprenorphine, tramadol, alfentanil, fentanyl, sufentanil, remifentanil, pethidine and methadone. No direct comparator was required for inclusion. Studies assessing the long-term efficacy of opioids during dialysis were excluded.
DATA COLLECTION AND ANALYSIS
This is a narrative systematic review and no meta-analysis was performed. The Grading of RECOMMENDATIONS Assessment, Development and Evaluation (GRADE) approach was used to assess the quality of the studies and to formulate guidelines.
MAIN RESULTS
Fifteen original articles were identified. Eight prospective and seven retrospective clinical studies were identified but no randomized controlled trials. No results were found for diamorphine, codeine, dihydrocodeine, buprenorphine, tramadol, dextropropoxyphene, methadone or remifentanil.
CONCLUSIONS
All of the studies identified have a significant risk of bias inherent in the study methodology and there is additional significant risk of publication bias. Overall evidence is of very low quality. The direct clinical evidence in cancer-related pain and renal impairment is insufficient to allow formulation of guidelines but is suggestive of significant differences in risk between opioids.
RECOMMENDATIONS
RECOMMENDATIONS regarding opioid use in renal impairment and cancer pain are made on the basis of pharmacokinetic data, extrapolation from non-cancer pain studies and from clinical experience. The risk of opioid use in renal impairment is stratified according to the activity of opioid metabolites, potential for accumulation and reports of successful or harmful use. Fentanyl, alfentanil and methadone are identified, with caveats, as the least likely to cause harm when used appropriately. Morphine may be associated with toxicity in patients with renal impairment. Unwanted side effects with morphine may be satisfactorily dealt with by either increasing the dosing interval or reducing the 24 hour dose or by switching to an alternative opioid.
Topics: Analgesics, Opioid; Clinical Trials as Topic; Europe; Humans; Neoplasms; Pain; Pain Measurement; Practice Guidelines as Topic; Renal Insufficiency; Severity of Illness Index
PubMed: 21708859
DOI: 10.1177/0269216311406313 -
The Journal of Rheumatology. Supplement Sep 2012To determine the efficacy and safety of antidepressants in pain management in patients with inflammatory arthritis (IA). (Review)
Review
OBJECTIVES
To determine the efficacy and safety of antidepressants in pain management in patients with inflammatory arthritis (IA).
METHODS
We searched the Cochrane Central Register of Controlled Trials, Medline, Embase, and PsychINFO for randomized controlled trials in adults with IA that compared any antidepressants (administered via any route) to another analgesic intervention or placebo. We also searched the 2008-2009 American College of Rheumatology and European League Against Rheumatism abstracts and performed a hand search of reference lists of relevant articles. Primary outcomes were patient-reported pain relief ≥ 30% and withdrawals due to adverse events. Two authors independently assessed methodological quality and extracted data. A risk of bias assessment was performed using methods recommended by the Cochrane Collaboration.
RESULTS
Eight trials (652 participants) in patients with rheumatoid arthritis (RA) and 1 trial in patients with ankylosing spondylitis (100 participants) were included in this review. The majority of studies were published in the late 1980s in patients with active disease receiving minimal disease-modifying antirheumatic drug therapy. All trials evaluated tricyclic antidepressants (TCA) and 2 studies included a selective serotonin uptake inhibitor. Seven of the 9 trials had high risk of bias, 2 were unclear, and metaanalysis was not performed due to trial heterogeneity. RA trials with short-term outcome (< 1 week) found no significant benefit of amitriptyline 25 mg in combination with dextropropoxyphene (DXP) 65 mg over placebo, and inferiority of amitriptyline + DXP versus DXP 130 mg [mean difference (MD) 10.0, 95% CI 0.4 to 19.6]. There was conflicting evidence regarding medium (1-6 wks) or longer-term (> 6 wks) benefits on pain. One trial in depressed patients with RA showed no significant difference between amitriptyline and paroxetine given for 8 weeks (65% vs 56% much or very much improved; RR 1.2, 95% CI 0.9 to 1.5). One trial found that amitriptyline was no better than placebo in reducing pain in patients with active AS over 2 weeks (MD -0.2, 95% CI -1.2 to 0.8). From 5 trials, withdrawals due to adverse events were not significantly different from placebo. However, there were significantly more minor adverse events in patients receiving TCA compared with those receiving a placebo (RR 2.3, 95% CI 1.2 to 4.4). These included somnolence, dizziness, dry mouth, and nausea.
CONCLUSION
Based upon 9 trials of high or unclear risk of bias, it is not possible to draw firm conclusions about the efficacy of TCA as analgesics for patients with IA. The use of these agents may be associated with adverse events that are generally mild and do not lead to cessation of treatment. High-quality trials are needed in this area.
Topics: Analgesics; Antidepressive Agents; Arthritis, Rheumatoid; Clinical Trials as Topic; Drug Therapy, Combination; Evidence-Based Medicine; Expert Testimony; Humans; International Cooperation; Pain; Pain Management
PubMed: 22942325
DOI: 10.3899/jrheum.120338 -
The Cochrane Database of Systematic... Nov 2011Despite improvements in the management of rheumatoid arthritis (RA), pain control is often inadequate even when inflammation is well controlled. (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Despite improvements in the management of rheumatoid arthritis (RA), pain control is often inadequate even when inflammation is well controlled.
OBJECTIVES
To assess the efficacy and safety of opioid analgesics for treating pain in patients with RA.
SEARCH METHODS
We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library), MEDLINE and EMBASE for studies to May 2010. We also searched the 2008 to 2009 American College of Rheumatology (ACR) and European League against Rheumatism (EULAR) abstracts and performed a handsearch of the reference lists of articles.
SELECTION CRITERIA
Studies were included if they were randomized or quasi-randomized controlled trials (RCTs or CCTs) which compared opioid therapy to another therapy (active or placebo) for pain in patients with RA. Outcomes of interest were pain, adverse effects, function and quality of life.
DATA COLLECTION AND ANALYSIS
Two review authors independently selected the studies for inclusion, extracted the data, and performed a risk of bias assessment.
MAIN RESULTS
Eleven studies (672 participants) were included in the review. Four studies assessed the efficacy of single doses of various opioid and non-opioid analgesics; a pooled analysis of these studies was not performed but in each study opioids reduced pain more than placebo. There were no differences between analgesic drugs in these studies.Seven studies were between one and six weeks in duration and assessed six different oral opioids (dextropropoxyphene, codeine, tramadol, tilidine, pentazocine, morphine), either alone or combined with non-opioid analgesics. The only strong opioid investigated was controlled-release morphine sulphate, in a single study with 20 participants. Six studies compared an opioid to placebo. Opioids were superior to placebo in patient-reported global impression of change (3 studies, 324 participants: relative risk (RR) 1.44, 95% CI 1.03 to 2.03) but not for the number of withdrawals due to inadequate analgesia (4 studies, 345 participants: RR 0.82, 95% CI 0.34 to 2.0). Adverse events (most commonly nausea, vomiting, dizziness and constipation) were more frequent in patients receiving opioids compared to placebo (4 studies, 371 participants: odds ratio 3.90, 95% CI 2.31 to 6.56); the pooled risk ratio for withdrawal due to adverse events was 2.67 (3 studies, 331 participants: 95% CI 0.52 to 13.75). One study compared an opioid (codeine with paracetamol) to an NSAID (diclofenac) and found no difference in efficacy or safety between interventions.
AUTHORS' CONCLUSIONS
There is limited evidence that weak oral opioids may be effective analgesics for some patients with RA, but adverse effects are common and may offset the benefits of this class of medications. There is insufficient evidence to draw conclusions regarding the use of weak opioids for longer than six weeks, or the role of strong opioids.
Topics: Adult; Aged; Analgesics, Opioid; Arthralgia; Arthritis, Rheumatoid; Humans; Middle Aged; Randomized Controlled Trials as Topic
PubMed: 22071805
DOI: 10.1002/14651858.CD003113.pub3 -
The Cochrane Database of Systematic... Mar 2015Oral analgesia is a convenient and widely used form of pain relief following caesarean section. It includes various medications used at different doses alone or in... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Oral analgesia is a convenient and widely used form of pain relief following caesarean section. It includes various medications used at different doses alone or in adjunction to other form of analgesia.
OBJECTIVES
To determine the effectiveness, safety and cost-effectiveness of oral analgesia for post-caesarean pain relief.
SEARCH METHODS
We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (31 July 2014) and reference lists of retrieved studies.
SELECTION CRITERIA
Randomised controlled trials (RCTs). Cluster-randomised trials were eligible for inclusion but none were identified. Quasi-randomised and cross-over trials were not eligible for inclusion.Interventions included oral medication given to women for post-caesarean pain relief compared with oral medication, or placebo/no treatment.
DATA COLLECTION AND ANALYSIS
Two review authors independently assessed for inclusion all the potential studies and independently assessed trial quality, extracted the data using the agreed data extraction form, and checked them for accuracy.
MAIN RESULTS
Eight small trials involving 962 women (out of 13 included trials) contributed data to the analysis, of which only four trials had low risk of bias.None of the included studies reported on 'adequate pain relief', which is one of this review's primary outcomes. 1. Opiod analgesics versus placeboBased on one trial involving 120 women, the effect of opioids versus placebo was not significant in relation to the need for additional pain relief (primary outcome) (risk ratio (RR) 0.33, 95% confidence interval (CI) 0.06 to 1.92), and the effect in terms of adverse drug effects outcomes was also uncertain (RR 6.58, 95% CI 0.38 to 113.96).Low (75 mg) and high (150 mg) doses of tramadol had a similar effect on the need for additional pain relief (RR 0.67, 95% CI 0.12 to 3.78 and RR 0.14, 95% CI 0.01 to 2.68, respectively, one study, 80 women). 2. Non-opioid analgesia versus placeboThe confidence interval for the lower requirement for additional analgesia (primary outcome) with the non-opioid analgesia group was wide and includes little or no effect (average RR 0.70, 95% CI 0.48 to 1.01, six studies, 584 women). However, we observed substantial heterogeneity due to the variety of non-opioid drugs used (I(2) = 85%). In a subgroup analysis of different drugs, only gabapentin use resulted in less need for additional pain relief (RR 0.34, 95% CI 0.23 to 0.51, one trial, 126 women). There was no difference in need for additional pain relief with the use of celexocib, ibuprofen, ketoprofen, naproxen, paracetamol. Maternal drug effects were more common with the use of non-opioid analgesics (RR 11.12, 95% CI 2.13 to 58.22, two trials, 267 women).Gabapentin 300 mg (RR 0.25, 95% CI 0.13 to 0.49, one study, 63 women) and 600 mg (RR 0.44, 95% CI 0.27 to 0.71, one study, 63 women) as well as ketoprofen 100 mg (RR 0.55, 95% CI 0.39 to 0.79, one study 72 women) were both more effective than placebo with respect to the need for additional pain relief. However, the 50 mg ketoprofen group and the placebo group did not differ in terms of the number of women requiring additional pain relief (RR 0.82, 95% CI 0.64 to 1.07, one study, 72 women). 3. Combination analgesics versus placeboOur pooled analysis for the effect of combination analgesics on the need for additional pain relief was RR 0.70 (95% CI 0.35 to 1.40, three trials, 242 women, I(2) = 69%). When comparing different drugs within the combination oral analgesics versus placebo comparison we observed subgroup differences (P = 0.05; I² = 65.8%). One trial comparing paracetamol plus codeine versus placebo resulted in fewer women requiring additional pain relief (RR 0.44, 95% CI 0.23 to 0.82, one trial, 65 women). However, there were no differences in the the number of women requiring additional pain relief when comparing paracetamol plus oxycodone versus placebo, or paracetamol plus propoxyphene (RR 1.00, 95% CI 0.78 to 1.28, one trial, 96 women and RR 0.65, 95% CI 0.11 to 3.69, one trial, 81 women, respectively).Maternal drug effects were more common in combination analgesics group versus placebo (RR 13.18, 95% CI 2.86 to 60.68, three trials, 252 women). 4. Opioid analgesics versus non-opioid analgesicsThe confidence interval for the effect on additional pain relief between opioid and non-opioid drugs was very wide (RR 0.51, 95% CI 0.07 to 3.51, one trial, 121 women). Side effects were more common with the use opioids versus non-opioids analgesics (RR 2.32, 95% CI 1.15 to 4.69, two trials 241 women). 5. Opioid analgesics versus combination analgesicsThere was no difference in need for additional pain relief in opioid analgesics versus combination analgesics based on one study involving 121 women comparing tramadol and paracetamol plus propoxyphene (RR 0.51, 95% CI 0.07 to 3.51). Maternal adverse effects also did not differ between the two groups (RR 6.74, 95% CI 0.39 to 116.79). 6. Non-opioid versus combination analgesicsThe need for additional pain relief was greater in the group of women who received non-opoid analgesics (RR 0.87, 95% CI 0.81 to 0.93, one trial, 192 women) compared with the group of women who received combination analgesics. Secondary outcomes not reported in the included studiesNo data were found on the following secondary outcomes: number of days in hospital post-operatively, re-hospitalisation due to incisional pain, fully breastfeeding on discharge, mixed feeding at discharge, incisional pain at six weeks after caesarean section, maternal post partum depression, effect (negative) on mother and baby interaction and cost of treatment.
AUTHORS' CONCLUSIONS
Eight trials with 962 women were included in the analysis, but only four trials were of high quality. All the trials were small. We carried out subgroup analysis for different drugs within the same group and for high versus low doses of the same drug. However, the relatively few studies (one to two trials) and numbers of women (40 to 136) limits the reliability of these subgroup analyses.Due to limited data available no conclusions can be made regarding the safest and the most effective form of oral analgesia for post-caesarean pain. Further studies are necessary.
Topics: Administration, Oral; Adult; Analgesia; Analgesics, Non-Narcotic; Analgesics, Opioid; Cesarean Section; Drug Therapy, Combination; Female; Humans; Pain, Postoperative; Pregnancy; Randomized Controlled Trials as Topic
PubMed: 25821010
DOI: 10.1002/14651858.CD010450.pub2 -
The Cochrane Database of Systematic... 2000Patient surveys have shown that postoperative pain is often not managed well, and there is a need to assess the efficacy and safety of commonly used analgesics as newer... (Review)
Review
BACKGROUND
Patient surveys have shown that postoperative pain is often not managed well, and there is a need to assess the efficacy and safety of commonly used analgesics as newer treatments become available. Dextropropoxyphene is one example of an opioid analgesic in current use, and is widely prescribed for pain relief in combination with paracetamol under names such as Co-proxamol and Distalgesic.
OBJECTIVES
To determine the analgesic efficacy and adverse effects of single dose oral Dextropropoxyphene alone and in combination with paracetamol (acetaminophen) for moderate to severe postoperative pain.
SEARCH STRATEGY
Published reports were identified from: Medline (1966 - November 1996), Biological Abstracts (1985 - 1996), Embase (1980 - 1996), the Cochrane Library (Issue 4 1996), and the Oxford Pain Relief Database (1954 - 1994). Additional studies were identified from the reference lists of retrieved reports. Date of the most recent searches: July 1998.
SELECTION CRITERIA
The inclusion criteria used were: full journal publication, postoperative pain, postoperative oral administration, adult patients, baseline pain of moderate to severe intensity, double-blind design, and random allocation to treatment groups which included dextropropoxyphene and placebo or a combination of dextropropoxyphene plus paracetamol and placebo.
DATA COLLECTION AND ANALYSIS
Data were extracted by two independent reviewers, and trials were quality scored. Summed pain intensity and pain relief data were extracted and converted into dichotomous information to yield the number of patients with at least 50% pain relief. This was used to calculate the relative benefit and number-needed-to-treat (NNT) for one patient to achieve at least 50% pain relief.
MAIN RESULTS
Six trials (440 patients) compared dextropropoxyphene with placebo and five (963 patients) compared dextropropoxyphene plus paracetamol 650 mg with placebo. For a single dose of dextropropoxyphene 65 mg in postoperative pain the NNT for at least 50% pain relief was 7.7 (95% confidence interval 4.6 to 22) when compared with placebo over 4-6 hours. For the equivalent dose of dextropropoxyphene combined with paracetamol 650 mg the NNT was 4.4 (3.5 to 5.6) when compared with placebo. These results were compared with those for other analgesics obtained from equivalent systematic reviews. Pooled data showed increased incidence of central nervous system adverse effects for dextropropoxyphene plus paracetamol compared with placebo.
REVIEWER'S CONCLUSIONS
The combination of dextropropoxyphene 65 mg with paracetamol 650 mg shows similar efficacy to tramadol 100 mg for single dose studies in postoperative pain but with a lower incidence of adverse effects. The same dose of paracetamol combined with 60 mg codeine appears more effective but, with the slight overlap in the 95% confidence intervals, this conclusion is not robust. Adverse effects of both combinations were similar. Ibuprofen 400 mg has a lower (better) NNT than both dextropropoxyphene 65 mg plus paracetamol 650 mg and tramadol 100 mg.
Topics: Acetaminophen; Analgesics, Non-Narcotic; Analgesics, Opioid; Dextropropoxyphene; Drug Therapy, Combination; Humans; Pain, Postoperative
PubMed: 10796793
DOI: 10.1002/14651858.CD001440 -
The Cochrane Database of Systematic... 2002Despite use in many countries of tapered methadone for detoxification from opiate, the evidence of efficacy to prevent relapse and promote lifestyle change has not been... (Review)
Review
BACKGROUND
Despite use in many countries of tapered methadone for detoxification from opiate, the evidence of efficacy to prevent relapse and promote lifestyle change has not been systematically evaluated.
OBJECTIVES
To determine whether tapered methadone is effective to manage withdrawal from opioids.
SEARCH STRATEGY
We searched: Cochrane Controlled Trial Register (Issue 1, 2000), MEDLINE (OVID 1966-2000), EMBASE (1980-2000); reference list of relevant articles; personal communication; conference abstracts; trials from pharmaceutical industry; Internet.
SELECTION CRITERIA
All randomised controlled trials on the use of tapered methadone versus all other detoxification treatments, placebo and different modalities of methadone detoxification programs for the treatment of opiate withdrawal.
DATA COLLECTION AND ANALYSIS
One reviewer assessed studies for inclusion and undertook data extraction. The overall process were confirmed by consultation between reviewers.
MAIN RESULTS
20 studies were included, with 1357 people randomised. 10 studies compared methadone with adrenergic agonists, 7 compared different modalities of methadone detoxification, 2 compared methadone with other opioid agonists, 1 study compared methadone with chlordiazepoxide one with placebo. 10 studies that compared methadone with adrenergic agonists showed clinical differences of the treatments; 6 studies that compared different methadone schedules, showed different withdrawal responses; 2 studies that compared methadone and other opioid agonists showed that methadyl acetate performed similarly to methadone, while propoxyphene produced more severe withdrawal symptoms and more drop-outs than methadone; chlordiazepoxide and methadone (1 study) resulted similar in terms of overall effectiveness; more severe withdrawal and more drop outs in the placebo group than in methadone one (1 study). The results indicate that tapered methadone and other medications used are effective although symptoms experienced differed according to the medication used and the program adopted. The medications are similar in terms of overall effectiveness. Improvements were achieved when other services supporting services were offered contemporaneously with detoxification.
REVIEWER'S CONCLUSIONS
Data from literature are hardly comparable; programs vary widely with regard to duration, design and treatment objectives, along with reporting impairing the application of meta-analysis. The studies included confirm that slow tapering with temporary substitution of long acting opioid can reduce withdrawal severity. Nevertheless the majority of patients relapsed to heroin use, abstinence cannot be considered a goal as heroin dependence is a chronic, relapsing disorder and the purpose of detoxification should be to remove or reduce dependence on heroin in a controlled and human fashion and not a treatment for heroin dependence.
Topics: Humans; Methadone; Narcotics; Randomized Controlled Trials as Topic; Substance Withdrawal Syndrome
PubMed: 11869660
DOI: 10.1002/14651858.CD003409 -
European Journal of Clinical... Apr 1998To determine the analgesic efficacy and adverse effects of single-dose oral dextropropoxyphene alone and in combination with paracetamol for moderate to severe... (Review)
Review
OBJECTIVE
To determine the analgesic efficacy and adverse effects of single-dose oral dextropropoxyphene alone and in combination with paracetamol for moderate to severe post-operative pain.
METHODS
Published reports were identified from a variety of electronic databases including MEDLINE, Biological Abstracts, EMBASE, the Cochrane Library and the Oxford Pain Relief Database. Additional studies were identified from the reference lists of retrieved reports. Summed pain intensity and pain relief data were extracted and converted into dichotomous information to yield the number of patients with at least 50% pain relief. This was used to calculate the relative benefit and number-needed-to-treat for one patient to achieve at least 50% pain relief. Six reports (440 patients) compared dextropropoxyphene with placebo and five (963 patients) compared dextropropoxyphene plus paracetamol 650 mg with placebo.
RESULTS
For a single dose of dextropropoxyphene 65 mg in post-operative pain the number-needed-to-treat for at least 50% pain relief was 7.7 (95% confidence interval 4.6 to 22) when compared with placebo over 4-6 h. For the equivalent dose of dextropropoxyphene in combination with paracetamol 650 mg the number-needed-to-treat was 4.4 (3.5 to 5.6) when compared with placebo. Pooled data showed increased incidence of central nervous system adverse effects for dextropropoxyphene plus paracetamol when compared with placebo. A rank order of single-dose analgesic effectiveness in post-operative pain of moderate to severe intensity obtained from similar systematic reviews is presented.
CONCLUSION
Dextropropoxyphene 65 mg plus paracetamol 650 mg has a similar analgesic efficacy to that of tramadol 100 mg but with a lower incidence of adverse effects. Ibuprofen 400 mg has a lower (better) number-needed-to-treat than both dextropropoxyphene 65 mg plus paracetamol 650 mg and tramadol 100 mg.
Topics: Acetaminophen; Analgesics, Non-Narcotic; Analgesics, Opioid; Dextropropoxyphene; Humans; Pain, Postoperative; Randomized Controlled Trials as Topic
PubMed: 9626913
DOI: 10.1007/s002280050430 -
The Cochrane Database of Systematic... Oct 2004Despite widespread use in many countries of tapered methadone for detoxification from opiate dependence, the evidence of efficacy to prevent relapse and promote... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Despite widespread use in many countries of tapered methadone for detoxification from opiate dependence, the evidence of efficacy to prevent relapse and promote lifestyle change has not been systematically evaluated.
OBJECTIVES
To determine whether tapered methadone is effective to manage opioids withdrawal.
SEARCH STRATEGY
We searched: the Cochrane Controlled Trials Register (Issue 1, 2000), MEDLINE (OVID 1966-2000), EMBASE (1980-2000); scan of reference list of relevant articles; personal communication; conference abstracts; unpublished trials from pharmaceutical industry; Internet (NIDA, Clinical Trials.org, BMJ).
SELECTION CRITERIA
All randomised controlled trials focused on tapered methadone (length of treatment max 30 days) versus all other pharmacological detoxification treatments, placebo and different modalities of methadone detoxification programs for the treatment of opiate withdrawal.
DATA COLLECTION AND ANALYSIS
One reviewer (LA) assessed studies for inclusion and undertook data extraction. Inclusion decisions and the overall process were confirmed by consultation between reviewers. Where possible analysis was carried out according to the "intention to treat" principles.
MAIN RESULTS
20 studies were included in the review, with 1357 participants. 10 studies compared methadone with adrenergic agonists, 7 studies compared different modalities of methadone detoxification, 2 studies compared methadone with other opioid agonists, 1 study with chlordiazepoxide, 1 with placebo. The conclusions of the 10 studies that compared methadone with adrenergic agonists showed no substantial clinical difference of the two treatments in terms of retention in treatment, degree of discomfort and detoxification success rates. The conclusions of the 6 studies that compare different methadone reduction schedules, showed that different types of methadone withdrawal schedule produce different responses in terms of withdrawal symptoms and severity of them. Regarding the studies that compare methadone with other opioid agonists, methadyl acetate performed similarly to methadone on most process and outcome measures, while methadone reduced severity of withdrawal and had fewer drop-outs than did propoxyphene. Using chlordiazepoxide vs methadone, the results suggest that the two drugs had similar results in terms of overall effectiveness. Comparing methadone with placebo more severe withdrawal and more drop outs were founded in the placebo group. The results indicate that tapered methadone and other medications used in the included studies are effective in the treatment of the heroin withdrawal syndrome, although symptoms experienced by subjects differed according to the medication used and the program adopted. It seems that regardless of which medication is selected for heroin detoxification, the rates of subsequent heroin abstinence are about equal. This suggests that the medications are similar in terms of overall effectiveness. Improvements were achieved when other services such as counseling and other supporting services were offered contemporaneously with detoxification.
REVIEWERS' CONCLUSIONS
Data from literature are hardly comparable; programs vary widely with regard to duration, design and treatment objectives, impairing the application of meta-analysis. Results of many outcomes could not be summarised because they were presented either in graphical form or provided only statistical tests and p-values. For most studies standard deviation for continuous variables were not provided. The studies included in this review confirm that slow tapering with temporary substitution of long acting opioids, accompanied by medical supervision and ancillary medications can reduce withdrawal severity. Nevertheless the majority of patients relapsed to heroin use. However this cannot be considered a goal for a detoxification as heroin dependence is a chronic, relapsing disorder and the goal of detoxification should be to remove or reduce dependence on heroin in a controlled and human fashion and not a treatment for heroin dependence.
Topics: Humans; Methadone; Narcotics; Opioid-Related Disorders; Randomized Controlled Trials as Topic; Substance Withdrawal Syndrome
PubMed: 15495052
DOI: 10.1002/14651858.CD003409.pub2