BACKGROUND: Complex regional pain syndrome (CRPS) is a chronic pain condition that usually occurs in a limb following trauma or surgery. It is characterised by persisting pain that is disproportionate in magnitude or duration to the typical course of pain after similar injury. There is currently no consensus regarding the optimal management of CRPS, although a broad range of interventions have been described and are commonly used. This is the first update of the original Cochrane review published in Issue 4, 2013.
OBJECTIVES: To summarise the evidence from Cochrane and non-Cochrane systematic reviews of the efficacy, effectiveness, and safety of any intervention used to reduce pain, disability, or both, in adults with CRPS.
METHODS: We identified Cochrane reviews and non-Cochrane reviews through a systematic search of Ovid MEDLINE, Ovid Embase, Cochrane Database of Systematic Reviews, CINAHL, PEDro, LILACS and Epistemonikos from inception to October 2022, with no language restrictions. We included systematic reviews of randomised controlled trials that included adults (≥18 years) diagnosed with CRPS, using any diagnostic criteria. Two overview authors independently assessed eligibility, extracted data, and assessed the quality of the reviews and certainty of the evidence using the AMSTAR 2 and GRADE tools respectively. We extracted data for the primary outcomes pain, disability and adverse events, and the secondary outcomes quality of life, emotional well-being, and participants' ratings of satisfaction or improvement with treatment. MAIN RESULTS: We included six Cochrane and 13 non-Cochrane systematic reviews in the previous version of this overview and five Cochrane and 12 non-Cochrane reviews in the current version. Using the AMSTAR 2 tool, we judged Cochrane reviews to have higher methodological quality than non-Cochrane reviews. The studies in the included reviews were typically small and mostly at high risk of bias or of low methodological quality. We found no high-certainty evidence for any comparison. There was low-certainty evidence that bisphosphonates may reduce pain intensity post-intervention (standardised mean difference (SMD) -2.6, 95% confidence interval (CI) -1.8 to -3.4, P = 0.001; I2 = 81%; 4 trials, n = 181) and moderate-certainty evidence that they are probably associated with increased adverse events of any nature (risk ratio (RR) 2.10, 95% CI 1.27 to 3.47; number needed to treat for an additional harmful outcome (NNTH) 4.6, 95% CI 2.4 to 168.0; 4 trials, n = 181). There was moderate-certainty evidence that lidocaine local anaesthetic sympathetic blockade probably does not reduce pain intensity compared with placebo, and low-certainty evidence that it may not reduce pain intensity compared with ultrasound of the stellate ganglion. No effect size was reported for either comparison. There was low-certainty evidence that topical dimethyl sulfoxide may not reduce pain intensity compared with oral N-acetylcysteine, but no effect size was reported. There was low-certainty evidence that continuous bupivacaine brachial plexus block may reduce pain intensity compared with continuous bupivacaine stellate ganglion block, but no effect size was reported. For a wide range of other commonly used interventions, the certainty in the evidence was very low and provides insufficient evidence to either support or refute their use. Comparisons with low- and very low-certainty evidence should be treated with substantial caution. We did not identify any RCT evidence for routinely used pharmacological interventions for CRPS such as tricyclic antidepressants or opioids.
AUTHORS' CONCLUSIONS: Despite a considerable increase in included evidence compared with the previous version of this overview, we identified no high-certainty evidence for the effectiveness of any therapy for CRPS. Until larger, high-quality trials are undertaken, formulating an evidence-based approach to managing CRPS will remain difficult. Current non-Cochrane systematic reviews of interventions for CRPS are of low methodological quality and should not be relied upon to provide an accurate and comprehensive summary of the evidence.
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.
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.
HINTERGRUND: Die antiepileptische Medikamente für die Behandlung von verschiedenen Arten von neuropathischem Schmerz verwendet worden, und manchmal Fibromyalgie. Unser Verständnis von Qualitätsstandards in der chronischen Schmerz Studien hat sich verbessert, neue Quellen der möglichen Befangenheit enthalten. Individuelle Cochrane-Reviews mit diesen neuen Standards einzelnen Antiepileptika geprüft. Eine frühe Kritik aus dieser Gruppe, die ursprünglich im Jahr 1998 veröffentlicht wurde, war 'Antikonvulsiva bei akuten und chronischen Schmerzen "betitelt. Diese Übersicht umfasst nun die neuropathischen Schmerzen Aspekt dieser ursprünglichen Kritik, die 2009 zurückgezogen wurde.
ZIELE: Um einen Überblick über die relative analgetische Wirksamkeit von Antiepileptika, die mit Placebo bei neuropathischen Schmerzen und Fibromyalgie verglichen wurden, bereitzustellen und zu unerwünschten Ereignissen bei ihrer Verwendung zu melden.
Methoden: Wir enthalten Bewertungen theCochrane Database of Systematic Reviews veröffentlicht bis August 2013 (Heft 7). Wir extrahierten Informationen von jeder Kritik an Maßnahmen der Wirksamkeit und der Schaden, und methodischen Details über die Anzahl der Teilnehmer, die Studiendauer und die Anrechnungsmethoden, um mögliche Verzerrungen in verfügbaren Daten zu beurteilen.
Wir analysierten Wirksamkeitsdaten für jede schmerzhafte Zustand in drei Stufen, je nach Ergebnis und die Freiheit von bekannten Quellen von Bias. Die erste Stufe erfüllt derzeit besten Standards - mindestens 50% Reduktion der Schmerzintensität über der Basislinie (oder dessen Äquivalent), ohne den Einsatz von letzten vorwärts (LOCF) für Aussteiger, einer Intention-to-treat (ITT)-Analyse, parallel durchgeführt Beobachtung Gruppe untersucht mit mindestens 200 Teilnehmern nachhaltig 8 Wochen oder mehr. Die zweite Stufe verwendet die Daten von mindestens 200 Teilnehmer in denen eine oder mehrere der oben genannten Bedingungen nicht erfüllt wurden. Die dritte Stufe des Beweises, um Daten von weniger als 200 Teilnehmern oder mit einigen wichtigen methodischen Probleme, die Auslegung begrenzt zusammen.
HAUPTERGEBNISSE: Es wurden keine Studien berichtet erstklassige Ergebnisse.
Nur für Gabapentin und Pregabalin fanden wir recht gute zweite Ebene Belege für die Wirksamkeit bei der schmerzhaften diabetischen Neuropathie und Postzosterschmerz. Darüber hinaus ist für Pregabalin, fanden wir Hinweise auf Wirksamkeit bei zentralen neuropathischen Schmerzen und Fibromyalgie. Punktschätzungen von Zahlen benötigt, um für einen zusätzlichen positiven Effekt (NNT) zu behandeln waren im Bereich von 4 bis 10 für das wichtigste Ergebnis der Schmerzintensität Reduktion gegenüber dem Ausgangs von 50% oder mehr.
Für andere Antiepileptika es keine Beweise (Clonazepam, Phenytoin), so wenig dafür, dass keine vernünftige Urteil könnte über die Wirksamkeit (Valproinsäure), niedrige Qualität Beweise wahrscheinlich mit einer Reihe von Vorurteilen zu überschätzen Wirksamkeit (Carbamazepin) zu sein, gemacht werden, oder vernünftige Qualität Beweise, die wenig oder keine Wirkung (Lamotrigin, Oxcarbazepin, Topiramat). Lacosamid aufgezeichnet, eine triviale statistische Überlegenheit gegenüber Placebo, es sei unzuverlässig zu dem Schluss, dass es keine Wirkung, wo es möglich war, hatte erhebliche Voreingenommenheit.
Alle Vorteile der Behandlung kam mit einem hohen Risiko von Nebenwirkungen und Entzugs aufgrund von Nebenwirkungen, aber schwerwiegende unerwünschte Ereignisse wurden nicht signifikant erhöht, jedoch mit Oxcarbazepin.
Schlussfolgerungen der Autoren: Klinische Studie Beweise unterstützt nur die Verwendung von Gabapentin und Pregabalin in einigen neuropathischen Schmerzen Bedingungen (schmerzhafter diabetischer Neuropathie, Postzosterschmerz und zentralen neuropathischen Schmerzen) und Fibromyalgie. Nur eine Minderheit der Menschen erreicht annehmbar gute Schmerzlinderung mit jeder Droge, aber es ist bekannt, dass die Lebensqualität und Funktion deutlich verbessert mit dem Ergebnis von mindestens 50% Reduktion der Schmerzintensität. Für andere Antiepileptika es keine Beweise, keine ausreichenden Beweise oder Hinweise auf einen Mangel an Wirkung, diese enthalten Carbamazepin. Erkenntnisse aus der klinischen Praxis und Erfahrung ist, dass einige Patienten können gute Ergebnisse mit anderen als Gabapentin oder Pregabalin Antiepileptika zu erreichen.
Es gibt keine festen Beweise, um die wichtigen Fragen rund um die pragmatischen Patienten sollte die Droge, und in welcher Reihenfolge die Drogen verwendet werden soll beantworten. Es ist eine klinische Wirksamkeit Forschungsagenda, Beweise über Strategien eher als Interventionen, die insgesamt besten Ergebnisse in einer Bevölkerung zu produzieren, in kürzester Zeit und zu den geringsten Kosten für Gesundheitsdienstleister.
Complex regional pain syndrome (CRPS) is a chronic pain condition that usually occurs in a limb following trauma or surgery. It is characterised by persisting pain that is disproportionate in magnitude or duration to the typical course of pain after similar injury. There is currently no consensus regarding the optimal management of CRPS, although a broad range of interventions have been described and are commonly used. This is the first update of the original Cochrane review published in Issue 4, 2013.
OBJECTIVES:
To summarise the evidence from Cochrane and non-Cochrane systematic reviews of the efficacy, effectiveness, and safety of any intervention used to reduce pain, disability, or both, in adults with CRPS.
METHODS:
We identified Cochrane reviews and non-Cochrane reviews through a systematic search of Ovid MEDLINE, Ovid Embase, Cochrane Database of Systematic Reviews, CINAHL, PEDro, LILACS and Epistemonikos from inception to October 2022, with no language restrictions. We included systematic reviews of randomised controlled trials that included adults (≥18 years) diagnosed with CRPS, using any diagnostic criteria. Two overview authors independently assessed eligibility, extracted data, and assessed the quality of the reviews and certainty of the evidence using the AMSTAR 2 and GRADE tools respectively. We extracted data for the primary outcomes pain, disability and adverse events, and the secondary outcomes quality of life, emotional well-being, and participants' ratings of satisfaction or improvement with treatment.
MAIN RESULTS:
We included six Cochrane and 13 non-Cochrane systematic reviews in the previous version of this overview and five Cochrane and 12 non-Cochrane reviews in the current version. Using the AMSTAR 2 tool, we judged Cochrane reviews to have higher methodological quality than non-Cochrane reviews. The studies in the included reviews were typically small and mostly at high risk of bias or of low methodological quality. We found no high-certainty evidence for any comparison. There was low-certainty evidence that bisphosphonates may reduce pain intensity post-intervention (standardised mean difference (SMD) -2.6, 95% confidence interval (CI) -1.8 to -3.4, P = 0.001; I2 = 81%; 4 trials, n = 181) and moderate-certainty evidence that they are probably associated with increased adverse events of any nature (risk ratio (RR) 2.10, 95% CI 1.27 to 3.47; number needed to treat for an additional harmful outcome (NNTH) 4.6, 95% CI 2.4 to 168.0; 4 trials, n = 181). There was moderate-certainty evidence that lidocaine local anaesthetic sympathetic blockade probably does not reduce pain intensity compared with placebo, and low-certainty evidence that it may not reduce pain intensity compared with ultrasound of the stellate ganglion. No effect size was reported for either comparison. There was low-certainty evidence that topical dimethyl sulfoxide may not reduce pain intensity compared with oral N-acetylcysteine, but no effect size was reported. There was low-certainty evidence that continuous bupivacaine brachial plexus block may reduce pain intensity compared with continuous bupivacaine stellate ganglion block, but no effect size was reported. For a wide range of other commonly used interventions, the certainty in the evidence was very low and provides insufficient evidence to either support or refute their use. Comparisons with low- and very low-certainty evidence should be treated with substantial caution. We did not identify any RCT evidence for routinely used pharmacological interventions for CRPS such as tricyclic antidepressants or opioids.
AUTHORS' CONCLUSIONS:
Despite a considerable increase in included evidence compared with the previous version of this overview, we identified no high-certainty evidence for the effectiveness of any therapy for CRPS. Until larger, high-quality trials are undertaken, formulating an evidence-based approach to managing CRPS will remain difficult. Current non-Cochrane systematic reviews of interventions for CRPS are of low methodological quality and should not be relied upon to provide an accurate and comprehensive summary of the evidence.
