Patients with chronic non-cancer pain who are prescribed and are taking opioids can have a history of long term high dose opioid use without effective pain relief. In those without good pain relief, reduction of prescribed opioid dose may be the desired and shared goal of both patient and clinician. Simple unsupervised reduction of opioid use is clinically challenging, and very difficult to achieve and maintain.
To investigate the effectiveness of different methods designed to achieve reduction or cessation of prescribed opioid use for the management of chronic non-cancer pain.
We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, and EMBASE from inception to 8th April 2013, as well as bibliographies.
Included studies had to be randomised controlled trials comparing opioid users receiving an intervention with a control group receiving treatment as usual, active control, or placebo. The aim of the study had to include a treatment goal of dose reduction or cessation of opioid medication.
Data collection and analysis
We sought data relating to prescribed opioid use, adverse events of opioid reduction, pain, and psychological and physical function.
Two studies provided information on 86 participants. One compared electroacupuncture with sham acupuncture for 20 minutes twice a week for six weeks; there was no difference between treatments. The other followed 11 weeks of cognitive behavioural therapy with either therapeutic interactive voice response through a computer for four months or usual treatment; the active group had a significant reduction in opioid use, while the usual care group had a significant increase.
Both included studies were at significant risk of bias because of their small size, together with other important issues, including blinding. Because of this risk and the paucity of relevant studies, no conclusions can be drawn regarding the effectiveness of interventions for opioid withdrawal in chronic non-cancer pain.
Interventions pour la réduction de l’utilisation d’opioïdes prescrits pour les douleurs chroniques non cancéreuses
Les patients atteints de douleurs chroniques non cancéreuses qui prennent des opioïdes prescrits peuvent avoir des antécédents de consommation d'opiacés à haute dose à long terme sans soulagement efficace de la douleur. Pour ces personnes chez qui la douleur n’est plus soulagée, la réduction des opioïdes peut être l’objectif désiré et partagé du patient et du clinicien. La réduction sans surveillance simple de l'utilisation d'opioïdes est cliniquement difficile, et très difficile à atteindre et à maintenir.
Etudier l'efficacité de différentes méthodes visant la réduction ou l'arrêt de la consommation d'opiacés prescrits pour la prise en charge des douleurs chroniques non cancéreuses.
Stratégie de recherche documentaire
Nous avons effectué des recherches dans le registre Cochrane des essais contrôlés (CENTRAL), MEDLINE et EMBASE de leur création jusqu'au 8 avril 2013, ainsi que les références bibliographiques.
Critères de sélection
Les études incluses devaient être des essais contrôlés randomisés comparant des consommateurs d'opiacés recevant une intervention à un groupe témoin recevant un traitement habituel, un contrôle actif ou placebo. L'objectif de cette étude devait inclure un objectif de traitement de réduction de la dose ou d'arrêt du traitement aux opiacés.
Recueil et analyse des données
Nous avons recherché des données relatives à l'utilisation d'opioïdes, les événements indésirables de la réduction des opiacés, la douleur et la fonction physique et psychologique.
Deux études ont fourni des informations sur 86 participants. Une comparait l'électro-acuponcture avec l'acupuncture simulée pour 20 minutes deux fois par semaine pendant six semaines; il n'y avait aucune différence entre les traitements. L'autre étude de 11 semaines faisait suite soit à une thérapie comportementale cognitive de quatre mois accompagnée d’une réponse thérapeutique vocale interactive par ordinateur soit à un traitement habituel; le groupe actif présentaient une réduction significative de la consommation d'opiacés, tandis que le groupe de soins habituels présentait une augmentation significative.
Conclusions des auteurs
Les deux études incluses présentaient un risque significatif de biais en raison de leur petite taille, en association avec d'autres questions importantes, y compris la mise en aveugle. En raison de ce risque et de la rareté des études pertinentes, aucune conclusion ne peut être tirée concernant l'efficacité des interventions pour le sevrage des opiacés dans les douleurs chroniques non cancéreuses.
Notes de traduction
Translated by: French Cochrane Centre
Translation supported by: Financeurs pour le Canada : Instituts de Recherche en Sant� du Canada, Minist�re de la Sant� et des Services Sociaux du Qu�bec, Fonds de recherche du Qu�bec-Sant� et Institut National d'Excellence en Sant� et en Services Sociaux; pour la France : Minist�re en charge de la Sant�
Reducing prescribed opioid use in chronic non-cancer pain
About 1 in 5 adults suffer from moderate or severe chronic pain that is not caused by cancer. Some people with this type of pain are treated with opioids (typically with drugs like morphine, codeine, oxycodone, fentanyl, or buprenorphine, either as tablets or as patches placed on the skin). It is not unusual for this medication to be ineffective or to stop working over time, and, sometimes, effective pain relief is not achieved despite doses being increased. Stopping using opioid drugs is not easy, especially when they have been used for some time, because stopping abruptly can cause unpleasant side effects. This review looked for high quality studies (randomised controlled trials) of treatments to help people safely stop taking opioids prescribed for their pain. Only two studies were found, and they investigated only 86 people. No conclusions can be drawn from this small amount of information. Non-randomised studies, not included in this review, do indicate that in most people intensive rehabilitation packages can bring about major reduction in opioid use. Reducing prescribed opioid use in chronic non-cancer pain is an important topic in need of more research.
Réduction de l’utilisation d’opioïdes prescrits pour les douleurs chroniques non cancéreuses
Environ 1 adulte sur 5 souffre de douleurs chroniques modérées ou sévères qui ne sont pas provoquées par le cancer. Certaines personnes atteintes de ce type de douleur sont traitées par des opioïdes (généralement avec des médicaments tels que la morphine, la codéine, l'oxycodone, le fentanyl, ou à la buprénorphine, soit sous forme de comprimés ou de timbres placés sur la peau). Il n'est pas rare que ces médicaments soit inefficaces ou arrêtent de fonctionner au cours du temps, et, parfois, un soulagement efficace de la douleur n'est pas obtenu malgré une augmentation des doses. L'arrêt des médicaments opioïdes n'est pas facile, en particulier lorsqu' ils ont été utilisés longtemps, car l'arrêt brutal peut entraîner des effets secondaires désagréables. Cette revue a recherché des études de haute qualité (essais contrôlés randomisés) sur les traitements aidant les personnes à arrêter les opioïdes prescrits pour la douleur en toute sécurité. Seules deux études ont été identifiées, et elles examinaient uniquement 86 patients. Aucune conclusion ne peut être tirée de cette petite quantité d'informations. Des études non-randomisées, non incluses dans cette revue indiquent que, pour la plupart des gens, les programmes de rééducation intensive peuvent entraîner une réduction importante dans la consommation d'opiacés. La diminution de la consommation d'opiacés prescrits pour les douleurs chroniques non cancéreuses est un important sujet qui nécessite des recherches supplémentaires.
Notes de traduction
Translated by: French Cochrane Centre
Translation supported by: Financeurs pour le Canada : Instituts de Recherche en Sant� du Canada, Minist�re de la Sant� et des Services Sociaux du Qu�bec, Fonds de recherche du Qu�bec-Sant� et Institut National d'Excellence en Sant� et en Services Sociaux; pour la France : Minist�re en charge de la Sant�
Резюме на простом языке
Уменьшение использования назначенных опиоидов при хронической нераковой боли
Около 1 человека из 5 взрослых страдают от умеренной или тяжелой хронической боли, которая не вызвана раком. Некоторых людей с таким типом боли лечат опиоидами (лекарствами, подобными морфину, кодеину, оксикодону, фентанилу или бупренорфину, либо в виде таблеток или в виде накожных пластырей). В некоторых случаях лекарственное лечение неэффективно или оно перестает работать с течением времени, и иногда эффективное обезболивание не достигается, несмотря на увеличение дозы. Прекратить использовать опиоидные лекарства нелегко, особенно, если их применяют в течение какого-то времени, т. к. внезапное прекращение их применения может вызвать неприятные побочные эффекты. Для подготовки этого обзора провели поиск исследований высокого качества (рандомизированных контролируемых испытаний), в которых изучали методы лечения, которые могли бы помочь людям безопасно прекратить прием опиоидов, назначенных для лечения боли. Были обнаружены только два исследования с участием 86 человек. Из такого небольшого количества информации сделать какие-либо выводы не представляется возможным. Нерандомизированные исследования, не включенные в этот обзор, действительно указывают, что у большинства людей интенсивные реабилитационные мероприятия могут привести к значительному сокращению использования опиоидов. Уменьшение использования назначенных опиоидов при хронической нераковой боли является важной темой и нуждается в дополнительных исследованиях.
Заметки по переводу
Перевод: Аглетдинова Эльнара Ленаровна. Редактирование: Юдина Екатерина Викторовна. Координация проекта по переводу на русский язык: Cochrane Russia - Кокрейн Россия (филиал Северного Кокрейновского Центра на базе Казанского федерального университета). По вопросам, связанным с этим переводом, пожалуйста, обращайтесь к нам по адресу: firstname.lastname@example.org
Chronic pain of moderate or severe intensity and lasting six months or longer affects around 20% of adults and imposes significant reduction in quality of life (Moore 2013). Opioids have long been used in the treatment of acute and cancer pain, and over the last two decades there has been a marked increase in their prescription for chronic non-cancer pain (CNCP), especially in the US, Australia, and Europe. Estimates of the numbers of people with chronic non-cancer pain treated with opioids are not commonly available, but one estimate for the UK indicates that almost one million people may use some form of opioid (Gallagher 2009).
Several randomised controlled trials suggested that opioids provide modest pain relief in the short to medium term (typical trial duration is 12 weeks; Kalso 2004; Furlan 2006). However, there is much less evidence that opioids provide long term pain relief in CNCP (ASIPP 2012; Noble 2010), especially when statistical imputation methods where withdrawal for any reason is regarded as treatment failure (and relevant to clinical practice) are used in favour of carrying the last observed pain readings to the end of the trial and using that measurement to estimate efficacy despite the patient not taking the medicine (not, therefore, relevant to clinical practice) (Moore 2012; Steiner 2011).
Adverse events, principally sedation, impaired cognitive function, depression, constipation, and bladder dysfunction, are also common during opioid therapy (Benyamin 2008), with up to 80% of users suffering at least one adverse event (BPS 2010; Moore 2005). Long-term opioid use can be associated with immune system depression, hormonal disturbances, and hyperalgesia (Benyamin 2008), as well as fractures (Miller 2011), and increased all-cause mortality in older people compared with other analgesics (Solomon 2010). Opioid use also carries risks of tolerance, dependence, and abuse.
Practicalities of the real world like prescribing restrictions for non-opioid analgesics, or guidelines that suggest early use of opioids, can mean that many patients are prescribed opioid drugs, sometimes inappropriately. The American Society of Interventional Pain Physicians suggests that the majority of patients who start chronic opioid treatment continue with the treatment throughout their life (ASIPP 2012). On occasion, opioid doses are increased as a result of insufficient analgesia or the development of tolerance (ie, requiring a higher dose to obtain the same therapeutic benefit). This can lead to patients being prescribed very high doses of opioids, but still without acceptable pain relief. American opioid sales quadrupled between 1999 and 2010 (ASIPP 2012). In the US, increased prescribing is associated with higher rates of overdose and overdose death (Paulozzi 2011), but with an indication that 60% of CNCP opioid deaths occurred while opioids were used as directed (ASIPP 2012). The link between opioid prescribing and opioid-related death is unclear, but rapid increases in opioid prescribing are being seen in Australia (Leong 2009), and in England there was a 101% increase in the number of prescriptions for strong opioids between 2004 and 2011 (NHS Information Centre 2012).
A number of professional societies worldwide have produced guidance advocating/promoting the judicious and careful use of opioids. The American Academy of Pain Medicine, the American Pain Society, and the American Society of Addiction Medicine jointly advise that health care providers should exercise caution when prescribing opioids, assessing circumstances and suitability on an individual basis (Chou 2009). Guidance in Washington State (Washington State Agency Medical Group 2010) has passed into law (HB2876 2010). Current UK guidance is typical in that it recognises that prescription opioids can lead to problem use, and that there is considerable uncertainty in the literature about any long term benefits of continued use. The British Pain Society guidance on opioids for persistent pain (BPS 2010) is particularly cautious. Similar cautions have been raised for prescribers in Australia (McDonough 2012).
There is growing concern that the widespread use of opioids has public health implications (Stannard 2012). The balance between benefit and risks generated during long term therapy with opioids suggests that it may be neither clinically effective nor in patients’ best interests to continue opioid prescription without adequate pain relief. There is, therefore, a potential need to facilitate and maintain opioid dose reduction. For many patients it is likely that long-term opioid treatment is continued even when benefit is not demonstrated, and greater patient benefits may accrue from opioid withdrawal. Patients who do not benefit from treatment in terms of pain, or who suffer unacceptable adverse events, should be helped to cease opioid treatment whilst concurrently addressing their pain (Ballantyne 2003).
There is a growing recognition that many patients will reach a state where the reduction of prescribed opioids is the desired and shared goal of both patient and clinician. This state is sometimes reached after a history of long term high dose opioid use, making simple unsupervised cessation clinically challenging, if not impossible. This may occur, at least in part, because of the reluctance of patient and prescriber to reduce opioid dose for fear of worsening pain, as well as issues of dependence and subsequent withdrawal symptoms.
There are many studies of methods of withdrawal from opioids; most, however, are undertaken in the context of addiction services for patients with an opioid abuse problem. Our interest here was in the planned reduction or total withdrawal of opioids prescribed for pain management. Common opioid reduction techniques in the addiction field are instructive and include opioid replacement stabilisation and dose tapering and may involve psychological treatments (Amato 2011). Inducing withdrawal under sedation using opioid antagonists such as naloxone, naltrexone, or nalmefene is possible (Gowing 2009; Gowing 2010) but is not recommended owing to unacceptable risks of adverse events. It is unclear whether similar interventions are effective when adjusted to CNCP in which treatment aims differ, or if other approaches are more appropriate.
Description of the condition
with chronic pain of a non-cancer-related origin
who are prescribed opioid medication for pain management
who have a treatment goal of dose reduction or cessation of opioid medicine
Description of the intervention
The intervention may be any clinical method that aims to facilitate opioid withdrawal or dose reduction as a compulsory or optional aspect of treatment, as either a primary or a secondary outcome. The intervention could be pharmacological, physiological, psychological, or another, as long its methods are documented clearly within the study.
How the intervention might work
Different methods will have different mechanisms. In particular, we expect non-pharmacological treatment aimed at opioid reduction to operate principally through behaviour change, and pharmacological methods to operate principally by reducing or managing the adverse events of opioid use or opioid withdrawal.
Why it is important to do this review
Increased prescribing of opioids is a problem because of their potential to cause harm, along with issues of limited relief and tolerance. Given the known risks of opioid therapy, it is appropriate to continue to prescribe opioid medicines only to those patients for whom the treatment produces acceptable benefits, weighed against any adverse events. Given evidence in many societies of huge increases in the use of medicinal opioids for CNCP, their limited effectiveness, and their adverse event profile, we can reasonably expect a large increase in patients seeking clinical help to reduce or halt opioid consumption. An evidence summary of the most effective methods is needed, along with guidance on treatment development.
To investigate the effectiveness of different methods designed to achieve reduction or cessation of prescribed opioid use for the management of CNCP.
Criteria for considering studies for this review
Types of studies
Included studies had to be randomised control trials (RCTs) comparing opioid users receiving an intervention with a control group receiving treatment as usual, active control, or placebo. The aim of the study had to include a treatment goal of dose reduction or cessation of opioid medicine.
Types of participants
Participants were adults (18 years of age or older) using prescription opioids for management of chronic non-cancer pain with a duration of at least three months. Pain conditions could include but were not limited to: neuropathic pain, myofacial pain, back pain, fibromyalgia, headache, abdominal, neck or musculoskeletal pain.
We excluded studies involving only participants with issues of addiction, abuse, dependence, or non-prescribed opioid use, and involving participants using opioids for pain relief during palliative care. This is because the aims of treatment for these populations differ substantially from those for the population of interest.
Types of interventions
We planned to include in this review a large variety of intervention types. Interventions could be based in pharmacology, physiology, psychology, spirituality, or another approach, provided that the underpinning methodology was well documented in the study and was valid. Eligible intervention types could include opioid antagonist treatment, dose tapering, or opioid replacement with other pain relieving medication. Interventions could also involve physical therapy, massage, disability management, complementary therapies, or psychological approaches such as cognitive behavioural therapy, counselling, and coping techniques.
We excluded studies encompassing only interventions specifically for opioid addiction, medication overuse, dependence, or withdrawal symptoms.
Types of outcome measures
We extracted relevant outcomes before treatment, immediately after treatment, and at follow-up, at least three months later but no longer than a year. If there were two follow-up time points, the later would be chosen.
The primary outcomes of this review are prescribed opioid use in adults, and the adverse events related to opioid reduction.
Secondary outcomes are symptom reporting of pain, psychological functioning, and physical functioning.
Search methods for identification of studies
We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, and EMBASE from inception to 8th April 2013, for RCTs meeting inclusion criteria, with no restrictions placed on language. See Appendix 1, Appendix 2, and Appendix 3 for the MEDLINE (via Ovid), EMBASE (via Ovid), and CENTRAL search strategies.
Searching other resources
We searched the reference lists of retrieved papers and carried out a citation search to identify any potentially eligible papers not found through the electronic search. We also contacted the authors of studies identified for inclusion to obtain additional data relevant to this review and not included in the published articles.
Data collection and analysis
Selection of studies
We filtered search results initially by title and abstract, and obtained full copies of potentially eligible studies. Two review authors read the studies to confirm eligibility, with disagreements discussed and mediated by a third review author if necessary. After the search was conducted, we limited the selection of studies to those published from 2000 onwards, to reflect the major growth in recent years in opioid prescribing for chronic non-cancer pain.
Data extraction and management
Two review authors extracted data using a standard data extraction form to include details of participants, intervention method and duration, quantity and type of opioid used, study design, and treatment outcomes. We discussed any discrepancies with a third review author.
Assessment of risk of bias in included studies
We assessed risk of bias in the included studies using the Cochrane Collaboration Risk of bias tool to assign judgements of high, low, or unclear risk of bias to sequence generation, allocation concealment, blinding, incomplete outcome data, selective reporting, and any other potential sources of bias in the included studies.
Measures of treatment effect
We planned to use risk ratio (RR) to establish statistical difference, and number needed to treat for an additional beneficial outcome (NNT) and number needed to treat for an additional harmful outcome (NNH) as absolute measures of benefit or harm.
We defined a 'responder' to treatment as a participant who experienced at least a 50% reduction in opioid consumption, or achieved complete opioid withdrawal or a reduction of their intake to below 'high' dose, which we identified as 120 mg/day oral morphine equivalent. Trials have previously shown that dose-related harms of taking more than 120 mg/day of opioid drugs outweigh the benefits (Braden 2010; Morasco 2010; Sullivan 2010), and published guidelines, including those of the American Pain Society and the American Academy of Pain Medicine (Chou 2009), and by the Washington State Agency Medical Group 2010, recommend a cut-off at 120 mg/day. A responder also had to have, at worst, no increase in pain as a result of the intervention. Both aspects of improvement had to be maintained for at least three months post intervention.
Unit of analysis issues
The unit of analysis was the individual patient.
Dealing with missing data
We used the intention-to-treat approach to deal with missing data. We would include in the analysis all participants who were randomised to treatment, and those for whom follow-up data were not available were assumed to be non-responders.
Assessment of heterogeneity
It was anticipated that there would be significant clinical heterogeneity between studies (participants, conditions, interventions), so we planned to pool data using a random-effects model.
Subgroup analysis and investigation of heterogeneity
We planned subgroup analyses to assess the effect of entry dose on intervention efficacy, and to compare outcomes between pain conditions or intervention type if sufficient data were available.
We planned to perform a sensitivity analysis should we suspect that studies with high risk of bias were significantly skewing results of a comparison, removing studies from the analysis to assess their influence.
Description of studies
Results of the search
We found 5195 reports in the original search; we identified 4285 reports after duplicates were removed. We identified ten potentially relevant reports from the titles and abstracts, and of these, three met the inclusion criteria of the review (Figure 1).
Two studies (three reports) were included in the analysis (Zheng 2008; Naylor 2010), with a total of 90 participants randomised to treatment, and 86 treated. One study (Naylor 2010) reported additional useful information in an earlier publication (Naylor 2008). Full details can be found in the Characteristics of included studies table.
In addition to published data, the authors of the two included studies provided additional data for the outcomes of pain and psychological functioning (Appendix 4).
Both of the studies were at significant risk of bias because of their small size, plus a number of other issues, including blinding (Figure 2).
Effects of interventions
The two included studies used different interventions, and so results were not pooled.
Zheng 2008 randomised participants to receive either real electroacupuncture (REA; n = 17) or sham electroacupuncture (SEA; n = 18) for 20 minutes twice a week for six weeks. Opioid consumption varied considerably within each group, and the mean consumption at baseline differed between groups, being 462 (± 463) mg/week in the REA group and 296 (± 288) mg/week in the SEA group. Participants in both groups who completed the six weeks of treatment (REA = 12; SEA = 14) reported a significant reduction in opioid consumption between baseline and the end of treatment at eight weeks, of 64% and 46% in the REA and SEA groups, respectively. In an intention-to-treat analysis, the reductions were 39% and 26%. The difference between groups was not statistically significant. At follow-up at 20 weeks (REA = 9; SEA = 14), opioid consumption had gradually increased in the REA group and was significantly higher at 20 weeks than at eight weeks, while in the SEA group there was no significant change.
Naylor 2010 compared therapeutic interactive voice response through a computer for four months with usual treatment, following cognitive behavioural therapy for 11 weeks. The experimental group (n = 26, 14 of whom were using opioids at baseline) reported a significant decrease in opioid use from baseline at both four- and eight-month follow-ups, with three participants stopping opioid use entirely. The control group (n = 25, 15 of whom were using opioids at baseline) significantly increased opioid consumption from baseline to the eight-month follow-up, and three more participants began opioid treatment. At eight-month follow-up, the difference in mean opioid dose was significant, with the experimental group using less than the control group.
Zheng 2008 reported a total of 33 adverse events during the treatment period with REA, and 19 with SEA, none of which were serious. Opioid-based adverse events decreased from baseline to eight weeks after treatment by 40% in the REA group and 45% in the SEA group.
Naylor 2010 did not report on adverse events, but contact with the authors confirmed that there were no adverse events associated with treatment.
These numbers are from data supplied by the authors (Appendix 4) and differ very slightly from the published data.
Zheng 2008 used the Visual Analogue Scale to assess pain intensity. Average pain at baseline was 4.9/10 in the experimental group and 5.6/10 in the control group, and post-treatment scores were 4.2 and 5.4, respectively. No differences were detected between groups. At 20 weeks average pain scores were 3.6 and 4.6.
Naylor 2010 analysed pain using the McGill Pain Questionnaire, reported in Naylor 2008 (Naylor 2010). The experimental group reported a decrease in typical pain from baseline to eight months from 5.7/10 to 3.4/10, and the control group from 6.8 to 5.7. The difference between groups was statistically significant.
Naylor 2010 reported physical function using the SF-36 Physical Function composite scale. The experimental group showed a small increase (from 31/100 to 40/100) in functioning over eight months, while the control group did not (29/100 to 31/100). The difference between groups was statistically significant.
Both studies utilised the Beck Depression Inventory as a measure of psychological functioning. The data are those provided by the authors.
Zheng 2008 reported a significant decrease in depression scores from baseline to post-treatment at 8 weeks in the REA group, from 18 to 17. Scores in the SEA group also decreased, from 19 to 15. At final measurement at 20 weeks, the real electro-acupuncture group mean score was 14, and the sham electro-acupuncture group mean score was 15. There was no significant difference between the groups.
Naylor 2010 reported a decrease in scores of depression across the study. The experimental group reported a mean of 17 at baseline, and 8.1 at 8 month follow-up. The maximum score fell from 29 to 22 in the same period. The control group scored an average of 19 at baseline, with a maximum of 51, decreasing to an average of 15, maximum 37, at 8 month follow-up.
Summary of main results
There were no adequate data from which to draw any conclusions from two small studies with different interventions and only 86 treated participants.
Overall completeness and applicability of evidence
Because of the very small number of included studies, it was decided to additionally investigate methods of prescription opioid reduction that were not randomised control trials, in case this was a more commonly used study design. We looked at papers from the existing search results and additional reference searching. Inclusion criteria remained the same as in the main search, excepting the criteria of randomised control design.
In contrast to the randomised evidence, there was a much larger body of evidence from observational studies. A three-week, outpatient, intensive, multidisciplinary pain rehabilitation program conducted at the Mayo Clinic Pain Rehabilitation Center demonstrated large reductions in medication use, particularly in use of opioids, in a number of publications in recent years. The three-week programme included stretching, goal setting, stress management, physical therapy, pain management, relaxation, and occupational therapy (Mayo 2013).
Typical opioid use in patients at admission was high, often above 40% and as high as 100%, and at discharge and follow-up was low, often below 10%. The analyses were retrospective or longitudinal, and not randomised, but represented an interesting body of additional data.
Results like these were obtained for 159 patients with fibromyalgia (Hooten 2007), for 383 patients after fusion or non-fusion spinal surgery, or no surgery (Crisostomo 2008), in a group of 411 patients with a wide range of age and non-cancer pain conditions (Darchuk 2010), and for 634 chronic pain patients of different smoking status (Hooten 2009). In a group of 213 patients all taking opioids on admission, the rate of opioid use at discharge was 7% and remained low for as long as six months after admission (Townsend 2008).
Change in medication use, including opioid medication use, is a common feature of multimodal and multicomponent programmes of cognitive behavioural therapy for chronic pain. The evidence for such programmes in improving disability status and reducing the impact of mental health outcomes is promising (Williams 2012). At present, however, it is not possible to extract and describe the components of such programmes for their effectiveness on medication consumption outcomes, although individual trials report positive effects. A challenge will be to determine methods of analysis, if possible, of such treatment packages with multiple components addressing multiple outcomes.
Others have sought evidence from literature reviews to prevent opioid over-use, and have put forward what is claimed to be an evidence-based algorithmic approach (Atluri 2012).
Legislation (HB2876 2010) has had a major effect on opioid prescribing in Washington State, where a de-facto limit of 120 mg oral morphine equivalent a day is suggested, with higher doses available after consultation with a specialist. An interim assessment showed that about half of physicians followed guidance on opioid prescribing, and that about 90% of them found it useful (DLI 2009). A more recent survey has shown large falls in opioid prescribing (27%), and in the proportion taking more than 120 mg a day oral morphine equivalents (35%), as well as in opioid-related deaths (50%) (Franklin 2012).
Quality of the evidence
The randomised trial evidence was generally of low quality.
Potential biases in the review process
We were not aware of any biases in the review process, although there was a potential for bias in searching for studies. While the intention to reduce opioid use may have been clear, possible interventions may have been disparate.
Agreements and disagreements with other studies or reviews
We found no other similar reviews.
Implications for practice
There were too few data in this review to permit any comments about implications for practice.
Implications for research
It is clear that more research is needed, but there was little guidance from the randomised studies included in this review to inform decisions about the design of future randomised trials, or what interventions they might investigate. Indeed it is a moot point whether testing individual interventions is appropriate, given that extant evidence from non-randomised studies indicates that a multifaceted multidisciplinary approach may be preferable.
The Mayo Clinic Pain Rehabilitation Center evidence indicated that a relatively short multifactorial rehabilitation programme might be a reasonable place to begin research, as that single centre appeared to obtain consistently good results. It is possible that the intensity of delivery of the multifactorial programme is as or more important than the details of specific components. In which case, the research agenda becomes one of replication in the first instance, followed by assessment and evaluation. Delivery of an intensive rehabilitation programme would probably have to be refined for particular locations and cultures.
We acknowledge the help of Jane Hayes and Jo Abbott in developing the search strategy, and the authors of the included studies in providing additional data.
(pain* or headache* or migraine* or neuralgia* or neuropath* or arthriti* or osteoarthriti*).mp.
1 or 2 or 3 or 4 or 5
exp Analgesics, Opioid/
(morphine or meperidine or methadone or buprenorphine or fentanyl or hydrocodone or oxycodone or codeine).mp.
(opioid* or opiate* or papaver).mp.
7 or 8 or 9 or 10
Opiate Substitution Treatment/
exp Narcotic Antagonists/
(diprenophine or nalmefene or nalorphine or naloxone or naltrexone or methadone or buprenorphine or clonidine or lofexidine or guanfacine).mp.
((cogniti* or behaviour* or behavior* or family or psychosocial*) adj5 (therap* or intervention*)).mp.
(counsel* or cope or coping).mp.
exp Physical Therapy Modalities/
exp Mind-Body Therapies/
(physical* adj5 therap*).mp.
(biofeedback* or massage* or acupuncture).mp.
pastoral care/ or spirituality/
(well being or well-being or relax* or accept* or meditat* or spiritual*).mp.
(withdraw* or wean* or detox* or cease or cessation or reduc* or taper* or stop* or terminat* or remove* or substitu*).mp.
12 or 13 or 14 or 15 or 16 or 17 or 18 or 19 or 20 or 21 or 22 or 23 or 24 or 25 or 26 or 27 or 28 or 29
6 and 11 and 30
randomized controlled trial.pt.
controlled clinical trial.pt.
clinical trials as topic.sh.
32 or 33 or 34 or 35 or 36 or 37 or 38
31 and 39
exp animals/ not humans.sh.
40 not 41
(post-operative or postoperative).mp.
42 not 43
limit 44 to ("young adult (19 to 24 years)" or "adult (19 to 44 years)" or "young adult and adult (19-24 and 19-44)" or "middle age (45 to 64 years)" or "middle aged (45 plus years)" or "all aged (65 and over)" or "aged (80 and over)")
Appendix 2. EMBASE search strategy (via Ovid)
exp chronic pain/ or exp intractable pain/
(pain* or headache* or migraine* or neuralgia* or neuropath* or arthriti* or osteoarthriti*).ti,ab.
1 or 2 or 3
exp narcotic analgesic agent/
exp narcotic agent/
(morphine or meperidine or methadone or buprenorphine or fentanyl or hydrocodone or oxycodone or codeine).ti,ab.
(opioid* or opiate* or papaver).ti,ab.
5 or 6 or 7 or 8
opiate substitution treatment/
exp narcotic antagonist/
(diprenorphine or nalmefene or nalorphine or naloxone or naltrexone or methadone or buprenorphine or clonidine or lofexidine or guanfacine).ti,ab.
((cogniti* or behaviour* or behavior* or family or psychosocial*) adj3 (therap* or intervention*)).ti,ab.
exp alternative medicine/
((physical* adj3 therap*) or physiotherap*).ti,ab.
(biofeedback* or massage* or acupuncture*).ti,ab.
(counsel* or cope or coping).ti,ab.
(well being or well-being or relax* or accept* or meditat* or spiritual*).ti,ab.
(withdraw* or wean* or detox* or cease or cessation or reduc* or taper* or stop* or terminat* or remove* or substitu*).ti,ab.
10 or 11 or 12 or 13 or 14 or 15 or 16 or 17 or 18 or 19 or 20 or 21 or 22 or 23 or 24 or 25 or 26
4 and 9 and 27
randomized controlled trial/
(crossover* or cross over* or cross-over*).mp.
(double* adj blind*).mp.
(singl* adj blind*).mp.
29 or 30 or 31 or 32 or 33 or 34 or 35 or 36 or 37 or 38 or 39 or 40 or 41
28 and 42
Appendix 3. CENTRAL search strategy
MeSH descriptor Pain explode all trees
(MeSH descriptor Fibromyalgia, this term only)
(MeSH descriptor Headache Disorders explode all trees)
(MeSH descriptor Arthritis explode all trees)
(pain* or headache* or migraine* or neuralgia* or neuropath* or arthriti* or osteoarthriti*)
(#1 OR #2 OR #3 OR #4 OR #5)
(MeSH descriptor Analgesics, Opioid explode all trees)
(morphine or meperidine or methadone or buprenorphine or fentanyl or hydrocodone or oxycodone or codeine)
(opioid* or opiate* or papaver)
(MeSH descriptor Narcotics explode all trees)
(#7 OR #8 OR #9 OR #10)
(MeSH descriptor Rehabilitation explode all trees)
Any MeSH descriptor with qualifier: RH
(MeSH descriptor Opiate Substitution Treatment explode all trees)
(MeSH descriptor Narcotic Antagonists explode all trees)
(diprenophine or nalmefene or nalorphine or naloxone or naltrexone or methadone or buprenorphine or clonidine or lofexidine or guanfacone)
(MeSH descriptor Psychotherapy explode all trees)
((cogniti* or behaviour* or behavior* or family or psychosocial*) near/5 (therap* or intervention*))
counsel* or cope or coping
MeSH descriptor Physical Therapy Modalities explode all trees
MeSH descriptor Mind-Body Therapies explode all trees
physical* near/5 therap*
biofeedback* or massage* or acupuncture*
(MeSH descriptor Pastoral Care, this term only)
(MeSH descriptor Spirituality, this term only)
(MeSH descriptor Adaptation, Psychological, this term only)
(well being or well-being or relax* or accept* or meditat* or spiritual*)
withdraw* or wean* or detox* or cease or cessation or reduc* or taper* or stop* or terminat* or remove* or substitu*
(12 OR #13 OR #14 OR #15 OR #16 OR #17 OR #18 OR #19 OR #20 OR #21 OR #22 OR #23 OR #24 OR #25 OR #26 OR #27 OR #28 OR #29 OR #30)
(#6 AND #11 AND #31), from 2002 to 2012
MeSH descriptor Pain, Postoperative explode all trees
(#32 AND NOT #33), from 2002 to 2012
Appendix 4. Additional data supplied by authors
McGill Typical Pain
5.7 ± 1.9
5.5 ± 1.7
4.1 ± 2.2
3.4 ± 2.4
6.8 ± 1.5
5.6 ± 1.6
5.7 ± 1.4
5.7 ± 1.7
16.7 ± 6.5
10.4 ± 6.4
8.1 ± 5.7
8.1 ± 4.8
18.6 ± 11.2
16.7 ± 11.2
16.3 ± 8.3
14.9 ± 8.7
Weeks 1, 2
4.2 ± 2.3
3.8 ± 1.7
3.6 ± 1.7
5.4 ± 2.4
5.0 ± 2.0
4.6 ± 2.1
18.4 ± 7.1
15.7 ± 9.7
17.1 ± 8.3
13.8 ± 8.1
14.1 ± 9.3
14.0 ± 7.5
19.0 ± 8.3
16.3 ± 10.9
15.3 ± 9.6
14.5 ± 10.8
15.2 ± 12.0
30 March 2016
Contact details amended.
Contributions of authors
Draft the protocol
Develop a search strategy
Search for studies (usually 2 authors)
Obtain copies of studies
Select which studies to include (2 + 1 arbiter)
Extract data from studies (2 authors)
Enter data into RevMan
Carry out the analysis
Interpret the analysis
Draft the final write-up of the review
Update the review
Content expert name
Author responsible for grammar and language
Declarations of interest
JW, EF, CE, and CS have no relevant interests to declare.
SD has received research support from charities and from government and industry sources at various times, but none are related to this review.
RAM has consulted for various pharmaceutical companies and has received lecture fees from pharmaceutical companies related to analgesics and other healthcare interventions, including (in the past five years) AstraZeneca, Eli Lilly, Flynn Pharma, Furtura Medical, Grünenthal, GSK, Horizon Pharma, Lundbeck, Menarini, MSD, Pfizer, Reckitt Bensckiser, Sanofi Aventis, Urgo, and Vifor Pharma.
RK has no conflict of interest in relation to the work under consideration for publication or relevant financial activities outside the submitted work, although he has attended advisory board meetings and has received honoraria or support to attend scientific meetings from several pharmaceutical companies, some of whom market opioids. RK is Chair, United Kingdom Clinical Pharmacy Association Pain Management Group; Chair, PAIN (Pharmacist Analgesia Interest Network); Member of IASP and several SIGs; Member of IASP task force on pharmacy undergraduate education; and Member of British Pain Society and several SIGs. RK has attended advisory board meetings, has received honoraria or support to attend scientific meetings, or has held research grants for Grünenthal, Reckitt Benckiser, Napp Pharmaceuticals, Pfizer, Astra Zeneca, and Astellas, some of which market opioids.
Sources of support
Oxford Pain Relief Trust, UK.
No sources of support supplied
Differences between protocol and review
We contacted the authors of studies identified for inclusion to obtain additional data relevant to this review and not included in the published articles. The original search for studies was intended to be completed without a time limit, but we limited inclusion to studies published in 2000 and later to reflect major changes since 2000 in prescribing of opioids to large numbers of people with chronic non-cancer pain; in this way, we worked to ensure that the review would have contemporary relevance.
Characteristics of studies
Characteristics of included studies [ordered by study ID]
11 weeks plus 120 days duration, randomised, standard care, controlled trial. Assessments at baseline, post intervention, 4 months, and 8 months post intervention
Diagnosis: chronic musculoskeletal pain
55 participants randomised, 51 participants received allocated intervention
Female 44, Male 7
Mean age 46 (SD ± 11.5) years
Prerandomisation cognitive behavioural therapy (all participants, n = 55)
Therapeutic Interactive Voice Response (n = 26)
Standard care (n = 25)
Prescribed medication use: dose and frequency of opioid analgesics, non-steroidal anti-inflammatory drugs, benzodiazepines, and antidepressants
Pain: Short Form McGIll Pain Questionnaire (MPQ), Pain Symptoms sub scale from the Treatment Outcomes in Pain Survey (TOPS)