-
The Cochrane Database of Systematic... Nov 2015Non-prescription (over-the-counter, or OTC) analgesics (painkillers) are used frequently. They are available in various brands, package sizes, formulations, and dose.... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Non-prescription (over-the-counter, or OTC) analgesics (painkillers) are used frequently. They are available in various brands, package sizes, formulations, and dose. They can be used for a range of different types of pain, but this overview reports on how well they work for acute pain (pain of short duration, usually with rapid onset). Thirty-nine Cochrane reviews of randomised trials have examined the analgesic efficacy of individual drug interventions in acute postoperative pain.
OBJECTIVES
To examine published Cochrane reviews for information about the efficacy of pain medicines available without prescription using data from acute postoperative pain.
METHODS
We identified OTC analgesics available in the UK, Australia, Canada, and the USA by examining online pharmacy websites. We also included some analgesics (diclofenac potassium, dexketoprofen, dipyrone) of importance in parts of the world, but not currently available in these jurisdictions.We identified systematic reviews by searching the Cochrane Database of Systematic Reviews (CDSR) on The Cochrane Library through a simple search strategy. All reviews were overseen by a single review group, had a standard title, and had as their primary outcome numbers of participants with at least 50% pain relief over four to six hours compared with placebo. From individual reviews we extracted the number needed to treat for an additional beneficial outcome (NNT) for this outcome for each drug/dose combination, and also calculated the success rate to achieve at least 50% of maximum pain relief. We also examined the number of participants experiencing any adverse event, and whether the incidence was different from placebo.
MAIN RESULTS
We found information on 21 different OTC analgesic drugs, doses, and formulations, using information from 10 Cochrane reviews, supplemented by information from one non-Cochrane review with additional information on ibuprofen formulations (high quality evidence). The lowest (best) NNT values were for combinations of ibuprofen plus paracetamol, with NNT values below 2. Analgesics with values close to 2 included fast acting formulations of ibuprofen 200 mg and 400 mg, ibuprofen 200 mg plus caffeine 100 mg, and diclofenac potassium 50 mg. Combinations of ibuprofen plus paracetamol had success rates of almost 70%, with dipyrone 500 mg, fast acting ibuprofen formulations 200 mg and 400 mg, ibuprofen 200 mg plus caffeine 100 mg, and diclofenac potassium 50 mg having success rates above 50%. Paracetamol and aspirin at various doses had NNT values of 3 or above, and success rates of 11% to 43%. We found no information on many of the commonly available low dose codeine combinations.The proportion of participants experiencing an adverse event were generally not different from placebo, except for aspirin 1000 mg and (barely) ibuprofen 200 mg plus caffeine 100 mg. For ibuprofen plus paracetamol, adverse event rates were lower than with placebo.
AUTHORS' CONCLUSIONS
There is a body of reliable evidence about the efficacy of some of the most commonly available drugs and doses widely available without prescription. The postoperative pain model is predominantly pain after third molar extraction, which is used as the industry model for everyday pain. The proportion of people with acute pain who get good pain relief with any of them ranges from around 70% at best to less than 20% at worst; low doses of some drugs in fast acting formulations were among the best. Adverse events were generally no different from placebo. Consumers can make an informed choice based on this knowledge, together with availability and price. Headache and migraine were not included in this overview.
Topics: Acute Pain; Administration, Oral; Analgesics; Humans; Nonprescription Drugs; Numbers Needed To Treat; Randomized Controlled Trials as Topic; Review Literature as Topic
PubMed: 26544675
DOI: 10.1002/14651858.CD010794.pub2 -
The Cochrane Database of Systematic... Jan 2014Duloxetine is a balanced serotonin and noradrenaline reuptake inhibitor licensed for the treatment of major depressive disorders, urinary stress incontinence and the... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Duloxetine is a balanced serotonin and noradrenaline reuptake inhibitor licensed for the treatment of major depressive disorders, urinary stress incontinence and the management of neuropathic pain associated with diabetic peripheral neuropathy. A number of trials have been conducted to investigate the use of duloxetine in neuropathic and nociceptive painful conditions. This is the first update of a review first published in 2010.
OBJECTIVES
To assess the benefits and harms of duloxetine for treating painful neuropathy and different types of chronic pain.
SEARCH METHODS
On 19th November 2013, we searched The Cochrane Neuromuscular Group Specialized Register, CENTRAL, DARE, HTA, NHSEED, MEDLINE, and EMBASE. We searched ClinicalTrials.gov for ongoing trials in April 2013. We also searched the reference lists of identified publications for trials of duloxetine for the treatment of painful peripheral neuropathy or chronic pain.
SELECTION CRITERIA
We selected all randomised or quasi-randomised trials of any formulation of duloxetine, used for the treatment of painful peripheral neuropathy or chronic pain in adults.
DATA COLLECTION AND ANALYSIS
We used standard methodological procedures expected by The Cochrane Collaboration.
MAIN RESULTS
We identified 18 trials, which included 6407 participants. We found 12 of these studies in the literature search for this update. Eight studies included a total of 2728 participants with painful diabetic neuropathy and six studies involved 2249 participants with fibromyalgia. Three studies included participants with depression and painful physical symptoms and one included participants with central neuropathic pain. Studies were mostly at low risk of bias, although significant drop outs, imputation methods and almost every study being performed or sponsored by the drug manufacturer add to the risk of bias in some domains. Duloxetine at 60 mg daily is effective in treating painful diabetic peripheral neuropathy in the short term, with a risk ratio (RR) for ≥ 50% pain reduction at 12 weeks of 1.73 (95% CI 1.44 to 2.08). The related NNTB is 5 (95% CI 4 to 7). Duloxetine at 60 mg daily is also effective for fibromyalgia over 12 weeks (RR for ≥ 50% reduction in pain 1.57, 95% CI 1.20 to 2.06; NNTB 8, 95% CI 4 to 21) and over 28 weeks (RR 1.58, 95% CI 1.10 to 2.27) as well as for painful physical symptoms in depression (RR 1.37, 95% CI 1.19 to 1.59; NNTB 8, 95% CI 5 to 14). There was no effect on central neuropathic pain in a single, small, high quality trial. In all conditions, adverse events were common in both treatment and placebo arms but more common in the treatment arm, with a dose-dependent effect. Most adverse effects were minor, but 16% of participants stopped the drug due to adverse effects. Serious adverse events were rare.
AUTHORS' CONCLUSIONS
There is adequate amounts of moderate quality evidence from eight studies performed by the manufacturers of duloxetine that doses of 60 mg and 120 mg daily are efficacious for treating pain in diabetic peripheral neuropathy but lower daily doses are not. Further trials are not required. In fibromyalgia, there is lower quality evidence that duloxetine is effective at similar doses to those used in diabetic peripheral neuropathy and with a similar magnitude of effect. The effect in fibromyalgia may be achieved through a greater improvement in mental symptoms than in somatic physical pain. There is low to moderate quality evidence that pain relief is also achieved in pain associated with depressive symptoms, but the NNTB of 8 in fibromyalgia and depression is not an indication of substantial efficacy. More trials (preferably independent investigator led studies) in these indications are required to reach an optimal information size to make convincing determinations of efficacy.Minor side effects are common and more common with duloxetine 60 mg and particularly with 120 mg daily, than 20 mg daily, but serious side effects are rare.Improved direct comparisons of duloxetine with other antidepressants and with other drugs, such as pregabalin, that have already been shown to be efficacious in neuropathic pain would be appropriate. Unbiased economic comparisons would further help decision making, but no high quality study includes economic data.
Topics: Adult; Analgesics; Chronic Pain; Diabetic Neuropathies; Duloxetine Hydrochloride; Fibromyalgia; Humans; Neuralgia; Randomized Controlled Trials as Topic; Thiophenes
PubMed: 24385423
DOI: 10.1002/14651858.CD007115.pub3 -
Medical Principles and Practice :... 2022Several forms of cannabinoids are currently being used to manage nausea and vomiting (N/V). Emerging cases of refractory N/V associated with chronic cannabis use among...
INTRODUCTION
Several forms of cannabinoids are currently being used to manage nausea and vomiting (N/V). Emerging cases of refractory N/V associated with chronic cannabis use among adults and older patients have been reported named cannabis hyperemesis syndrome (CHS). CHS is a condition that leads to repeated and severe N/V in long-term users of cannabinoids.
OBJECTIVE
The aim of this study was to outline current treatments for the management of CHS.
METHODS
A systematic review was conducted using PubMed, Ovid MEDLINE, Cochrane Central, EMBASE, and Google Scholar. Databases were used to search for articles on CHS published from January 2009 to June 2021, yielding 225 results of which 17 were deemed relevant and underwent review by 2 separate reviewers.
RESULTS
The duration of cannabis administration ranged between 6 months to 11 years may precipitate symptoms of CHS. The Rome IV diagnostic criteria of CHS require cannabinoid use and persistence of N/V symptoms for at least the past 6 months. Cannabis cessation is noted to be the most successful management, but other treatments also demonstrated symptom relief; these include hot water hydrotherapy, topical capsaicin cream, haloperidol, droperidol, benzodiazepines, propranolol, and aprepitant administration.
CONCLUSION
More research on CHS is needed to enhance knowledge translation, education, and create awareness in the medical community on the side effects of cannabinoids and to propose the best treatment options.
Topics: Adult; Analgesics; Cannabinoids; Cannabis; Humans; Marijuana Abuse; Syndrome; Vomiting
PubMed: 34724666
DOI: 10.1159/000520417 -
The Cochrane Database of Systematic... Dec 2018Inadequate pain management after surgery increases the risk of postoperative complications and may predispose for chronic postsurgical pain. Perioperative ketamine may... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Inadequate pain management after surgery increases the risk of postoperative complications and may predispose for chronic postsurgical pain. Perioperative ketamine may enhance conventional analgesics in the acute postoperative setting.
OBJECTIVES
To evaluate the efficacy and safety of perioperative intravenous ketamine in adult patients when used for the treatment or prevention of acute pain following general anaesthesia.
SEARCH METHODS
We searched CENTRAL, MEDLINE and Embase to July 2018 and three trials registers (metaRegister of controlled trials, ClinicalTrials.gov and the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP)) together with reference checking, citation searching and contact with study authors to identify additional studies.
SELECTION CRITERIA
We sought randomised, double-blind, controlled trials of adults undergoing surgery under general anaesthesia and being treated with perioperative intravenous ketamine. Studies compared ketamine with placebo, or compared ketamine plus a basic analgesic, such as morphine or non-steroidal anti-inflammatory drug (NSAID), with a basic analgesic alone.
DATA COLLECTION AND ANALYSIS
Two review authors searched for studies, extracted efficacy and adverse event data, examined issues of study quality and potential bias, and performed analyses. Primary outcomes were opioid consumption and pain intensity at rest and during movement at 24 and 48 hours postoperatively. Secondary outcomes were time to first analgesic request, assessment of postoperative hyperalgesia, central nervous system (CNS) adverse effects, and postoperative nausea and vomiting. We assessed the evidence using GRADE and created a 'Summary of findings' table.
MAIN RESULTS
We included 130 studies with 8341 participants. Ketamine was given to 4588 participants and 3753 participants served as controls. Types of surgery included ear, nose or throat surgery, wisdom tooth extraction, thoracotomy, lumbar fusion surgery, microdiscectomy, hip joint replacement surgery, knee joint replacement surgery, anterior cruciate ligament repair, knee arthroscopy, mastectomy, haemorrhoidectomy, abdominal surgery, radical prostatectomy, thyroid surgery, elective caesarean section, and laparoscopic surgery. Racemic ketamine bolus doses were predominantly 0.25 mg to 1 mg, and infusions 2 to 5 µg/kg/minute; 10 studies used only S-ketamine and one only R-ketamine. Risk of bias was generally low or uncertain, except for study size; most had fewer than 50 participants per treatment arm, resulting in high heterogeneity, as expected, for most analyses. We did not stratify the main analysis by type of surgery or any other factor, such as dose or timing of ketamine administration, and used a non-stratified analysis.Perioperative intravenous ketamine reduced postoperative opioid consumption over 24 hours by 8 mg morphine equivalents (95% CI 6 to 9; 19% from 42 mg consumed by participants given placebo, moderate-quality evidence; 65 studies, 4004 participants). Over 48 hours, opioid consumption was 13 mg lower (95% CI 10 to 15; 19% from 67 mg with placebo, moderate-quality evidence; 37 studies, 2449 participants).Perioperative intravenous ketamine reduced pain at rest at 24 hours by 5/100 mm on a visual analogue scale (95% CI 4 to 7; 19% lower from 26/100 mm with placebo, high-quality evidence; 82 studies, 5004 participants), and at 48 hours by 5/100 mm (95% CI 3 to 7; 22% lower from 23/100 mm, high-quality evidence; 49 studies, 2962 participants). Pain during movement was reduced at 24 hours (6/100 mm, 14% lower from 42/100 mm, moderate-quality evidence; 29 studies, 1806 participants), and 48 hours (6/100 mm, 16% lower from 37 mm, low-quality evidence; 23 studies, 1353 participants).Results for primary outcomes were consistent when analysed by pain at rest or on movement, operation type, and timing of administration, or sensitivity to study size and pain intensity. No analysis by dose was possible. There was no difference when nitrous oxide was used. We downgraded the quality of the evidence once if numbers of participants were large but small-study effects were present, or twice if numbers were small and small-study effects likely but testing not possible.Ketamine increased the time for the first postoperative analgesic request by 54 minutes (95% CI 37 to 71 minutes), from a mean of 39 minutes with placebo (moderate-quality evidence; 31 studies, 1678 participants). Ketamine reduced the area of postoperative hyperalgesia by 7 cm² (95% CI -11.9 to -2.2), compared with placebo (very low-quality evidence; 7 studies 333 participants). We downgraded the quality of evidence because of small-study effects or because the number of participants was below 400.CNS adverse events occurred in 52 studies, while 53 studies reported of absence of CNS adverse events. Overall, 187/3614 (5%) participants receiving ketamine and 122/2924 (4%) receiving control treatment experienced an adverse event (RR 1.2, 95% CI 0.95 to 1.4; high-quality evidence; 105 studies, 6538 participants). Ketamine reduced postoperative nausea and vomiting from 27% with placebo to 23% with ketamine (RR 0.88, 95% CI 0.81 to 0.96; the number needed to treat to prevent one episode of postoperative nausea and vomiting with perioperative intravenous ketamine administration was 24 (95% CI 16 to 54; high-quality evidence; 95 studies, 5965 participants).
AUTHORS' CONCLUSIONS
Perioperative intravenous ketamine probably reduces postoperative analgesic consumption and pain intensity. Results were consistent in different operation types or timing of ketamine administration, with larger and smaller studies, and by higher and lower pain intensity. CNS adverse events were little different with ketamine or control. Perioperative intravenous ketamine probably reduces postoperative nausea and vomiting by a small extent, of arguable clinical relevance.
Topics: Acute Pain; Adult; Analgesics; Analgesics, Opioid; Central Nervous System Diseases; Humans; Hyperalgesia; Injections, Intravenous; Ketamine; Morphine; Pain Measurement; Pain, Postoperative; Postoperative Nausea and Vomiting; Randomized Controlled Trials as Topic
PubMed: 30570761
DOI: 10.1002/14651858.CD012033.pub4 -
BMJ Clinical Evidence Feb 2014Dystonia is usually a lifelong condition with persistent pain and disability. Focal dystonia affects a single part of the body; generalised dystonia can affect most or... (Review)
Review
INTRODUCTION
Dystonia is usually a lifelong condition with persistent pain and disability. Focal dystonia affects a single part of the body; generalised dystonia can affect most or all of the body. It is more common in women, and some types of dystonia are more common in people of Ashkenazi descent.
METHODS AND OUTCOMES
We conducted a systematic review and aimed to answer the following clinical questions: What are the effects of drug treatments, surgical treatments, and physical treatments for focal and generalised dystonia? We searched: Medline, Embase, The Cochrane Library, and other important databases up to September 2013 (Clinical Evidence reviews are updated periodically; please check our website for the most up-to-date version of this review). We included harms alerts from relevant organisations such as the US Food and Drug Administration (FDA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA).
RESULTS
We found 19 studies that met our inclusion criteria. We performed a GRADE evaluation of the quality of evidence for interventions.
CONCLUSIONS
In this systematic review, we present information relating to the effectiveness and safety of the following interventions: acupuncture, amantadine, baclofen, benzatropine, biofeedback, botulinum toxins, bromocriptine, carbamazepine, carbidopa/levodopa, clonazepam, clozapine, deep brain stimulation of thalamus and globus pallidus, diazepam, gabapentin, haloperidol, lorazepam, myectomy (for focal dystonia), occupational therapy, ondansetron, physiotherapy, pregabalin, procyclidine, selective peripheral denervation (for focal dystonia), speech therapy, tizanidine, trazodone hydrochloride, and trihexyphenidyl.
Topics: Analgesics; Anticonvulsants; Dystonia; Humans; Physical Therapy Modalities; Speech Therapy; Treatment Outcome
PubMed: 25347760
DOI: No ID Found -
The Cochrane Database of Systematic... Jan 2017This review is an update of 'Topical capsaicin (high concentration) for chronic neuropathic pain in adults' last updated in Issue 2, 2013. Topical creams with capsaicin... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
This review is an update of 'Topical capsaicin (high concentration) for chronic neuropathic pain in adults' last updated in Issue 2, 2013. Topical creams with capsaicin are used to treat peripheral neuropathic pain. Following application to the skin, capsaicin causes enhanced sensitivity, followed by a period with reduced sensitivity and, after repeated applications, persistent desensitisation. High-concentration (8%) capsaicin patches were developed to increase the amount of capsaicin delivered; rapid delivery was thought to improve tolerability because cutaneous nociceptors are 'defunctionalised' quickly. The single application avoids noncompliance. Only the 8% patch formulation of capsaicin is available, with a capsaicin concentration about 100 times greater than conventional creams. High-concentration topical capsaicin is given as a single patch application to the affected part. It must be applied under highly controlled conditions, often following local anaesthetic, due to the initial intense burning sensation it causes. The benefits are expected to last for about 12 weeks, when another application might be made.
OBJECTIVES
To review the evidence from controlled trials on the efficacy and tolerability of topically applied, high-concentration (8%) capsaicin in chronic neuropathic pain in adults.
SEARCH METHODS
For this update, we searched CENTRAL, MEDLINE, Embase, two clinical trials registries, and a pharmaceutical company's website to 10 June 2016.
SELECTION CRITERIA
Randomised, double-blind, placebo-controlled studies of at least 6 weeks' duration, using high-concentration (5% or more) topical capsaicin to treat neuropathic pain.
DATA COLLECTION AND ANALYSIS
Two review authors independently searched for studies, extracted efficacy and adverse event data, and examined issues of study quality and potential bias. Where pooled analysis was possible, we used dichotomous data to calculate risk ratio and numbers needed to treat for one additional event, using standard methods.Efficacy outcomes reflecting long-duration pain relief after a single drug application were from the Patient Global Impression of Change (PGIC) at specific points, usually 8 and 12 weeks. We also assessed average pain scores over weeks 2 to 8 and 2 to 12 and the number of participants with pain intensity reduction of at least 30% or at least 50% over baseline, and information on adverse events and withdrawals.We assessed the quality of the evidence using GRADE and created a 'Summary of findings' table.
MAIN RESULTS
We included eight studies, involving 2488 participants, two more studies and 415 more participants than the previous version of this review. Studies were of generally good methodological quality; we judged only one study at high risk of bias, due to small size. Two studies used a placebo control and six used 0.04% topical capsaicin as an 'active' placebo to help maintain blinding. Efficacy outcomes were inconsistently reported, resulting in analyses for most outcomes being based on less than complete data.For postherpetic neuralgia, we found four studies (1272 participants). At both 8 and 12 weeks about 10% more participants reported themselves much or very much improved with high-concentration capsaicin than with 'active' placebo, with point estimates of numbers needed to treat for an additional beneficial outcome (NNTs) of 8.8 (95% confidence interval (CI) 5.3 to 26) with high-concentration capsaicin and 7.0 (95% CI 4.6 to 15) with 'active' placebo (2 studies, 571 participants; moderate quality evidence). More participants (about 10%) had average 2 to 8-week and 2 to 12-week pain intensity reductions over baseline of at least 30% and at least 50% with capsaicin than control, with NNT values between 10 and 12 (2 to 4 studies, 571 to 1272 participants; very low quality evidence).For painful HIV-neuropathy, we found two studies (801 participants). One study reported the proportion of participants who were much or very much improved at 12 weeks (27% with high-concentration capsaicin and 10% with 'active' placebo). For both studies, more participants (about 10%) had average 2 to 12-week pain intensity reductions over baseline of at least 30% with capsaicin than control, with an NNT of 11 (very low quality evidence).For peripheral diabetic neuropathy, we found one study (369 participants). It reported about 10% more participants who were much or very much improved at 8 and 12 weeks. One small study of 46 participants with persistent pain following inguinal herniorrhaphy did not show a difference between capsaicin and placebo for pain reduction (very low quality evidence).We downgraded the quality of the evidence for efficacy outcomes by one to three levels due to sparse data, imprecision, possible effects of imputation methods, and susceptibility to publication bias.Local adverse events were common, but not consistently reported. Serious adverse events were no more common with active treatment (3.5%) than control (3.2%). Adverse event withdrawals did not differ between groups, but lack of efficacy withdrawals were somewhat more common with control than active treatment, based on small numbers of events (six to eight studies, 21 to 67 events; moderate quality evidence, downgraded due to few events). No deaths were judged to be related to study medication.
AUTHORS' CONCLUSIONS
High-concentration topical capsaicin used to treat postherpetic neuralgia, HIV-neuropathy, and painful diabetic neuropathy generated more participants with moderate or substantial levels of pain relief than control treatment using a much lower concentration of capsaicin. These results should be interpreted with caution as the quality of the evidence was moderate or very low. The additional proportion who benefited over control was not large, but for those who did obtain high levels of pain relief, there were usually additional improvements in sleep, fatigue, depression, and quality of life. High-concentration topical capsaicin is similar in its effects to other therapies for chronic pain.
Topics: Administration, Topical; Adult; Analgesics; Capsaicin; Chronic Pain; Diabetic Neuropathies; HIV Infections; Humans; Neuralgia; Neuralgia, Postherpetic; Numbers Needed To Treat; Ointments; Pain, Postoperative; Randomized Controlled Trials as Topic
PubMed: 28085183
DOI: 10.1002/14651858.CD007393.pub4 -
Journal of Orthopaedic Surgery (Hong... 2023Duloxetine is a serotonin and norepinephrine reuptake inhibitor (SNRI) with clinical efficacy in chronic pain conditions. In this study, we aim to evaluate the... (Review)
Review
Duloxetine is a serotonin and norepinephrine reuptake inhibitor (SNRI) with clinical efficacy in chronic pain conditions. In this study, we aim to evaluate the analgesic effect and safety of duloxetine in total knee arthroplasty (TKA). A systematic search was completed on MEDLINE, PsycINFO, and Embase from inception to December 2022 to find relevant articles. We used Cochrane methodology to evaluate the bias of included studies. Investigated outcomes included postoperative pain, opioid consumption, adverse events (AEs), range of motion (ROM), emotional and physical function, patient satisfaction, patient-controlled analgesia (PCA), knee-specific outcomes, wound complications, skin temperature, inflammatory markers, length of stay, and incidence of manipulations. Nine articles involving 942 participants were included in our systematic review. Out of nine papers, eight were randomized clinical trials and one was a retrospective study. The results of these studies indicated the analgesic effect of duloxetine on postoperative pain, which was measured using numeric rating scale and visual analogue scale. Deluxetine was also effective in reducing the morphine requirement and wound complications and enhancing patient satisfaction after surgery. However, the results on ROM, PCA, and knee-specific outcomes were contraventional. Deluxetine was generally safe without serious AEs. The most common AEs included headache, nausea, vomiting, dry mouth, and constipation. Duloxetine may be an effective treatment option for postoperative pain following TKA, but further rigorously designed and well-controlled randomized trials are required.
Topics: Humans; Duloxetine Hydrochloride; Arthroplasty, Replacement, Knee; Retrospective Studies; Pain, Postoperative; Analgesics, Opioid; Randomized Controlled Trials as Topic
PubMed: 37279647
DOI: 10.1177/10225536231177482 -
The Cochrane Database of Systematic... Sep 2015This is an updated version of the original Cochrane overview published in Issue 9, 2011. That overview considered both efficacy and adverse events, but adverse events... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
This is an updated version of the original Cochrane overview published in Issue 9, 2011. That overview considered both efficacy and adverse events, but adverse events are now dealt with in a separate overview.Thirty-nine Cochrane reviews of randomised trials have examined the analgesic efficacy of individual drug interventions in acute postoperative pain. This overview brings together the results of those individual reviews and assesses the reliability of available data.
OBJECTIVES
To summarise the efficacy of pharmaceutical interventions for acute pain in adults with at least moderate pain following surgery who have been given a single dose of oral analgesic.
METHODS
We identified systematic reviews in the Cochrane Database of Systematic Reviews in The Cochrane Library through a simple search strategy. All reviews were overseen by a single review group, had a standard title, and had as their primary outcome the number of participants with at least 50% pain relief over four to six hours compared with placebo. For individual reviews, we extracted the number needed to treat for an additional beneficial outcome (NNT) for this outcome for each drug/dose combination, and also the percentage of participants achieving at least 50% maximum pain relief, the mean of mean or median time to remedication, and the percentage of participants remedicating by six, eight, 12, or 24 hours. Where there was adequate information for pairs of drug and dose (at least 200 participants, in at least two studies), we defined the addition of four comparisons of typical size (400 participants in total) with zero effect as making the result potentially subject to publication bias and therefore unreliable.
MAIN RESULTS
The overview included 39 separate Cochrane Reviews with 41 analyses of single dose oral analgesics tested in acute postoperative pain models, with results from about 50,000 participants in approximately 460 individual studies. The individual reviews included only high-quality trials of standardised design, methods, and efficacy outcome reporting. No statistical comparison was undertaken.Reliable results (high quality information) were obtained for 53 pairs of drug and dose in painful postsurgical conditions; these included various fixed dose combinations, and fast acting formulations of some analgesics. NNTs varied from about 1.5 to 20 for at least 50% maximum pain relief over four to six hours compared with placebo. The proportion of participants achieving this level of benefit varied from about 30% to over 70%, and the time to remedication varied from two hours (placebo) to over 20 hours. Good (low) NNTs were obtained with ibuprofen 200 mg plus paracetamol (acetaminophen) 500 mg (NNT compared with placebo 1.6; 95% confidence interval 1.5 to 1.8), ibuprofen fast acting 200 mg (2.1; 1.9 to 2.3); ibuprofen 200 mg plus caffeine 100 mg (2.1; 1.9 to 3.1), diclofenac potassium 50 mg (2.1; 1.9 to 2.5), and etoricoxib 120 mg (1.8; 1.7 to 2.0). For comparison, ibuprofen acid 400 mg had an NNT of 2.5 (2.4 to 2.6). Not all participants had good pain relief and, for many pairs of drug and dose, 50% or more did not achieve at least 50% maximum pain relief over four to six hours.Long duration of action (eight hours or greater) was found for etoricoxib 120 mg, diflunisal 500 mg, paracetamol 650 mg plus oxycodone 10 mg, naproxen 500/550 mg, celecoxib 400 mg, and ibuprofen 400 mg plus paracetamol 1000 mg.There was no evidence of analgesic effect for aceclofenac 150 mg, aspirin 500 mg, and oxycodone 5 mg (low quality evidence). No trial data were available in reviews of acemetacin, meloxicam, nabumetone, nefopam, sulindac, tenoxicam, and tiaprofenic acid. Inadequate amounts of data were available for nine drugs and doses, and data potentially susceptible to publication bias for 13 drugs and doses (very low quality evidence).
AUTHORS' CONCLUSIONS
There is a wealth of reliable evidence on the analgesic efficacy of single dose oral analgesics. Fast acting formulations and fixed dose combinations of analgesics can produce good and often long-lasting analgesia at relatively low doses. There is also important information on drugs for which there are no data, inadequate data, or where results are unreliable due to susceptibility to publication bias. This should inform choices by professionals and consumers.
Topics: Acute Pain; Administration, Oral; Adult; Analgesics; Humans; Pain, Postoperative
PubMed: 26414123
DOI: 10.1002/14651858.CD008659.pub3 -
British Journal of Clinical Pharmacology Sep 2015It is common to advise that analgesics, and especially non-steroidal anti-inflammatory drugs (NSAIDs), be taken with food to reduce unwanted gastrointestinal adverse... (Review)
Review
AIMS
It is common to advise that analgesics, and especially non-steroidal anti-inflammatory drugs (NSAIDs), be taken with food to reduce unwanted gastrointestinal adverse effects. The efficacy of single dose analgesics depends on producing high, early, plasma concentrations; food may interfere with this. This review sought evidence from single dose pharmacokinetic studies on the extent and timing of peak plasma concentrations of analgesic drugs in the fed and fasting states.
METHODS
A systematic review of comparisons of oral analgesics in fed and fasting states published to October 2014 reporting kinetic parameters of bioavailability, time to maximum plasma concentration (tmax ), and its extent (Cmax ) was conducted. Delayed-release formulations were not included.
RESULTS
Bioavailability was not different between fasted and fed states. Food typically delayed absorption for all drugs where the fasting tmax was less than 4 h. For the common analgesics (aspirin, diclofenac, ibuprofen, paracetamol) fed tmax was 1.30 to 2.80 times longer than fasted tmax . Cmax was typically reduced, with greater reduction seen with more rapid absorption (fed Cmax only 44-85% of the fasted Cmax for aspirin, diclofenac, ibuprofen and paracetamol).
CONCLUSION
There is evidence that high, early plasma concentrations produces better early pain relief, better overall pain relief, longer lasting pain relief and lower rates of remedication. Taking analgesics with food may make them less effective, resulting in greater population exposure. It may be time to rethink research priorities and advice to professionals, patients and the public.
Topics: Acetaminophen; Administration, Oral; Anti-Inflammatory Agents, Non-Steroidal; Aspirin; Biological Availability; Dipyrone; Drug Liberation; Food-Drug Interactions; Humans
PubMed: 25784216
DOI: 10.1111/bcp.12628 -
The Cochrane Database of Systematic... Sep 2020Pain after caesarean sections (CS) can affect the well-being of the mother and her ability with her newborn. Conventional pain-relieving strategies are often underused... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Pain after caesarean sections (CS) can affect the well-being of the mother and her ability with her newborn. Conventional pain-relieving strategies are often underused because of concerns about the adverse maternal and neonatal effects. Complementary alternative therapies (CAM) may offer an alternative for post-CS pain.
OBJECTIVES
To assess the effects of CAM for post-caesarean pain.
SEARCH METHODS
We searched Cochrane Pregnancy and Childbirth's Trials Register, LILACS, PEDro, CAMbase, ClinicalTrials.gov and the WHO International Clinical Trials Registry Platform (ICTRP) (6 September 2019), and checked the reference lists of retrieved articles.
SELECTION CRITERIA
Randomised controlled trials (RCTs), including quasi-RCTs and cluster-RCTs, comparing CAM, alone or associated with other forms of pain relief, versus other treatments or placebo or no treatment, for the treatment of post-CS pain.
DATA COLLECTION AND ANALYSIS
Two review authors independently performed study selection, extracted data, assessed risk of bias and assessed the certainty of evidence using GRADE.
MAIN RESULTS
We included 37 studies (3076 women) which investigated eight different CAM therapies for post-CS pain relief. There is substantial heterogeneity among the trials. We downgraded the certainty of evidence due to small numbers of women participating in the trials and to risk of bias related to lack of blinding and inadequate reporting of randomisation processes. None of the trials reported pain at six weeks after discharge. Primary outcomes were pain and adverse effects, reported per intervention below. Secondary outcomes included vital signs, rescue analgesic requirement at six weeks after discharge; all of which were poorly reported, not reported, or we are uncertain as to the effect Acupuncture or acupressure We are very uncertain if acupuncture or acupressure (versus no treatment) or acupuncture or acupressure plus analgesia (versus placebo plus analgesia) has any effect on pain because the quality of evidence is very low. Acupuncture or acupressure plus analgesia (versus analgesia) may reduce pain at 12 hours (standardised mean difference (SMD) -0.28, 95% confidence interval (CI) -0.64 to 0.07; 130 women; 2 studies; low-certainty evidence) and 24 hours (SMD -0.63, 95% CI -0.99 to -0.26; 2 studies; 130 women; low-certainty evidence). It is uncertain whether acupuncture or acupressure (versus no treatment) or acupuncture or acupressure plus analgesia (versus analgesia) has any effect on the risk of adverse effects because the quality of evidence is very low. Aromatherapy Aromatherapy plus analgesia may reduce pain when compared with placebo plus analgesia at 12 hours (mean difference (MD) -2.63 visual analogue scale (VAS), 95% CI -3.48 to -1.77; 3 studies; 360 women; low-certainty evidence) and 24 hours (MD -3.38 VAS, 95% CI -3.85 to -2.91; 1 study; 200 women; low-certainty evidence). We are uncertain if aromatherapy plus analgesia has any effect on adverse effects (anxiety) compared with placebo plus analgesia. Electromagnetic therapy Electromagnetic therapy may reduce pain compared with placebo plus analgesia at 12 hours (MD -8.00, 95% CI -11.65 to -4.35; 1 study; 72 women; low-certainty evidence) and 24 hours (MD -13.00 VAS, 95% CI -17.13 to -8.87; 1 study; 72 women; low-certainty evidence). Massage We identified six studies (651 women), five of which were quasi-RCTs, comparing massage (foot and hand) plus analgesia versus analgesia. All the evidence relating to pain, adverse effects (anxiety), vital signs and rescue analgesic requirement was very low-certainty. Music Music plus analgesia may reduce pain when compared with placebo plus analgesia at one hour (SMD -0.84, 95% CI -1.23 to -0.46; participants = 115; studies = 2; I = 0%; low-certainty evidence), 24 hours (MD -1.79, 95% CI -2.67 to -0.91; 1 study; 38 women; low-certainty evidence), and also when compared with analgesia at one hour (MD -2.11, 95% CI -3.11 to -1.10; 1 study; 38 women; low-certainty evidence) and at 24 hours (MD -2.69, 95% CI -3.67 to -1.70; 1 study; 38 women; low-certainty evidence). It is uncertain whether music plus analgesia has any effect on adverse effects (anxiety), when compared with placebo plus analgesia because the quality of evidence is very low. Reiki We are uncertain if Reiki plus analgesia compared with analgesia alone has any effect on pain, adverse effects, vital signs or rescue analgesic requirement because the quality of evidence is very low (one study, 90 women). Relaxation Relaxation may reduce pain compared with standard care at 24 hours (MD -0.53 VAS, 95% CI -1.05 to -0.01; 1 study; 60 women; low-certainty evidence). Transcutaneous electrical nerve stimulation TENS (versus no treatment) may reduce pain at one hour (MD -2.26, 95% CI -3.35 to -1.17; 1 study; 40 women; low-certainty evidence). TENS plus analgesia (versus placebo plus analgesia) may reduce pain compared with placebo plus analgesia at one hour (SMD -1.10 VAS, 95% CI -1.37 to -0.82; 3 studies; 238 women; low-certainty evidence) and at 24 hours (MD -0.70 VAS, 95% CI -0.87 to -0.53; 108 women; 1 study; low-certainty evidence). TENS plus analgesia (versus placebo plus analgesia) may reduce heart rate (MD -7.00 bpm, 95% CI -7.63 to -6.37; 108 women; 1 study; low-certainty evidence) and respiratory rate (MD -1.10 brpm, 95% CI -1.26 to -0.94; 108 women; 1 study; low-certainty evidence). We are uncertain if TENS plus analgesia (versus analgesia) has any effect on pain at six hours or 24 hours, or vital signs because the quality of evidence is very low (two studies, 92 women).
AUTHORS' CONCLUSIONS
Some CAM therapies may help reduce post-CS pain for up to 24 hours. The evidence on adverse events is too uncertain to make any judgements on safety and we have no evidence about the longer-term effects on pain. Since pain control is the most relevant outcome for post-CS women and their clinicians, it is important that future studies of CAM for post-CS pain measure pain as a primary outcome, preferably as the proportion of participants with at least moderate (30%) or substantial (50%) pain relief. Measuring pain as a dichotomous variable would improve the certainty of evidence and it is easy to understand for non-specialists. Future trials also need to be large enough to detect effects on clinical outcomes; measure other important outcomes as listed lin this review, and use validated scales.
Topics: Acupressure; Acupuncture Analgesia; Adolescent; Adult; Analgesia, Obstetrical; Analgesics; Aromatherapy; Bias; Cesarean Section; Combined Modality Therapy; Complementary Therapies; Female; Humans; Massage; Music Therapy; Pain, Postoperative; Placebos; Pregnancy; Randomized Controlled Trials as Topic; Relaxation Therapy; Therapeutic Touch; Transcutaneous Electric Nerve Stimulation; Young Adult
PubMed: 32871021
DOI: 10.1002/14651858.CD011216.pub2