Journal Logo

General Section

Interactions between analgesic drug therapy and mindfulness-based interventions for chronic pain in adults: protocol for a systematic scoping review

Park, Rexa; Mohiuddin, Mohammeda; Poulin, Patriciab; Salomons, Timc,d; Edwards, Roberte; Nathan, Howardb; Haley, Chrisa; Gilron, Iana,f,d,g,*

Author Information
doi: 10.1097/PR9.0000000000000793
  • Open
  • Editor's Choice


1. Introduction

Chronic pain is a significant health problem given its prevalence, impact on quality of life, economic burden, and difficult management. Chronic pain is generally described as pain that persists over 3 months or past the normal time for tissue healing.15 However, in most people, the duration of pain is much longer.9,37 For example, one Canadian study found that over 45% of people with chronic pain have experienced pain for over 10 years.37 Chronic pain has major negative impacts on daily living activities and work-related outcomes, such as employment status and days missed from work.4 Individuals living with chronic pain have double the risk of suicide compared with those who do not.27,38 Chronic pain is one of the most common reasons for medical visits and is estimated to affect 1.5 billion people worldwide.8,10,12 Approximately 30% of adults in the United States and up to 19% of adults in Canada experience chronic pain.20,36 Chronic pain costs $635 billion per year in the United States and $43 billion per year in Canada when direct health care and productivity costs are considered, which exceed the annual costs from cancer, heart disease, and diabetes.20,28 Despite the limited evidence supporting the efficacy and safety of opioids for chronic noncancer pain, they have been the mainstay of treatment in the United States for the past 2 decades. The high opioid prescriptions have been associated with increases in opioid-related mortality due to accidental overdose and in the number of individuals with opioid-misuse disorders.3,21 This emphasizes the importance of advancing knowledge on nonopioid treatment regimens, including alternatives, which might replace or enhance the effectiveness of drug therapies.

The use of mindfulness-based interventions (MBIs) for the management of chronic pain has received considerable attention in the last 3 decades due to its potentially beneficial effects on pain intensity, depressive symptoms, quality of life, as well as emerging evidence regarding its safety.23,30,31,35,41 Recent studies have consistently shown a positive relationship between mindfulness and positive psychological health, with clinical uses including the treatment of depression, stress reduction, and tobacco cessation—as well as for chronic pain.17,25,39 Although there are variations between mindfulness techniques, their basic procedures and goals are similar.7 Mindfulness involves nonjudgmentally observing one's own thoughts, feelings, and sensations in the present moment without attempting to change them.24 A well-studied MBI is mindfulness-based stress reduction.22 Mindfulness-based stress reduction is an evidence-based, structured 8-week group program consisting of 8 weekly 2-hour workshops and a full day session half-way through the course.32,34 Mindfulness-based stress reduction includes instruction on mindfulness meditation, body scans, and hatha yoga to facilitate awareness of physical and mental experiences. In addition, participants commit to perform daily 45-minute homework tasks that include meditation and yoga.22,32

A large body of evidence supports the possible benefits of MBIs for patients with chronic pain.11,23,26,31,35. Although mindfulness may directly reduce pain intensity, the primary goal of mindfulness is to improve functioning and distress.35 The practice of mindfulness is believed to result in the spontaneous uncoupling of the sensory component from the cognitive emotional component of pain.24 This emotional component can amplify pain and contribute to the development of depression and anxiety, as well as contribute to avoidance of activity, thereby exacerbating disability.7 Thus, understanding and controlling the cognitive and emotional components of pain aims to reduce the amount of suffering and disability.

Given the well-recognized limitations of any one modality of treatment for chronic pain, the evolving concept of multimodal therapy has led to the concurrent use of 2 or more different treatment modalities for chronic pain. However, the evidence base to support the rational use of specific treatment combinations is quite limited.21 Because MBIs and drug therapies likely reduce pain by different mechanisms, their combined use could provide added benefit. However, there have been no reports of interaction effects of the combination of MBIs with any specific analgesic drugs. Thus, we aim to perform a systematic scoping review to systematically review MBI trials with respect to concurrent drug therapy used during each trial, evaluate the current state of the literature, and look at the evidence for the efficacy and safety of MBI and drug combination therapy compared with monotherapy.

2. Objectives

The objective of this overview is to review the available clinicals trials of MBIs for chronic pain to describe the landscape of mindfulness-based trials with respect to drug therapy and evaluate the available evidence on the interactions between MBIs and various drug treatments.

3. Methods

This protocol is developed in accordance with PRISMA-P guidelines33 and will be registered in the PROSPERO register (protocol number pending).

3.1. Sources of evidence

We will conduct a detailed search on CENTRAL, MEDLINE, EMBASE, and PsycINFO from their inception until the date the searches are run. The search will include terms relating to MBIs, chronic pain, and relevant clinical pain outcomes. The search strategy for MEDLINE was developed in consultation with a librarian specializing in literature searches.

We will also review the bibliographies of any randomized controlled trials identified for relevance, as well as search clinical trial databases ( and the World Health Organization International Clinical Trials Registry Platform to identify additional published or unpublished data.

3.2. Report selection

3.2.1. Types of studies

The review will include randomized controlled trials that evaluate the efficacy of MBIs in the treatment of chronic pain. Studies with less than 10 participants will be excluded to minimize small study bias.

3.2.2. Types of participants

We will include studies with adults aged 18 years and over-reporting any type of chronic pain for at least 3 months. Chronic pain can include persistent (eg, chronic low back pain and fibromyalgia) and intermittent (eg, migraine) pain.

3.2.3. Types of interventions

We will focus on any MBI administered for the treatment of chronic pain. To provide a discrete set of results, we will focus on “mindfulness,” “mindfulness-based stress reduction,” “mindfulness-oriented recovery enhancement,” “mindfulness-based cognitive therapy,” “mindfulness meditation,” “mindfulness awareness in body-oriented therapy,” or any intervention that is a modification of these mindfulness-based therapies. This will allow the current state of mindfulness trials with respect to concomitant drug therapy to be summarized. We will exclude studies where mindfulness is only a component of the intervention.

3.2.4. Comparators

Studies comparing the MBI can be compared with usual care, wait-list control, or an active comparator.

3.3. Data collection, extraction, and management

Two reviewers will independently evaluate studies for eligibility. Screening will be performed on titles and abstracts, and full-text screening will be performed on citations felt to be potentially eligible. Disagreements between the reviewers will be resolved by discussion and consensus. If necessary, a third reviewer will be consulted.

Data from selected studies will be extracted independently by two reviewers using standardized extraction forms. The forms will capture information about the chronic pain conditions of participants, type of mindfulness-based treatment investigated, primary and secondary outcome measures, and other study characteristics.

3.4. Outcomes

3.4.1. Primary outcomes

Our primary outcomes will include the following: (1) What concomitant analgesic drug therapies the trial participants were receiving, (2) if and how trials controlled for what concomitant analgesic drug therapies the participants were receiving, and (3) if trials analyzed the interaction between the MBI and the concomitant drug therapies the trial participants were receiving. As an example, we will report on any subgroup analyses on the effect of the MBI with or without a specific concomitant analgesic drug. For the trials that analyzed the interaction between mindfulness and drug therapy, we will also look at what the results were in terms of pain intensity and pain relief (eg, MBI and drug combination therapy compared with monotherapy in reducing pain intensity).

3.4.2. Secondary outcomes

Secondary outcomes include how MBI and drug combination treatment differs from monotherapy in managing secondary features of chronic pain such as depression, physical and mental health-related quality of life, and functional disability. Secondary outcomes will also include participants experiencing any adverse event and participants experiencing any serious adverse event.

3.5. Analysis plan

3.5.1. Analysis of outcomes

A descriptive approach will be used to report the primary outcomes because the outcomes will likely be varied across studies. We will also use a descriptive approach to evaluate how the combination treatment differs from the individual treatments in managing secondary features of chronic pain such as depression, physical and mental health-related quality of life, and functional disability. Analysis of trial outcomes will be categorized according to the type of control intervention used in the trial. The interaction between MBIs and drug therapy will be evaluated to the degree that each trial accounted for drug effects.

3.5.2. Analysis of risk of bias

Risk of bias for each study will be independently assessed by 2 reviewers using criteria outlined in the Cochrane Handbook for Systematic Review of Interventions (25). For any studies that include both an MBI and an analgesic drug as the trial interventions, risk of bias will be assessed separately for each intervention. Disagreements between reviewers will be resolved with discussion and consensus. If necessary, a third reviewer will be consulted. We will assess the following for each study: (1) random sequence generation for possible selection bias; (2) allocation concealment for possible selection bias; (3) blinding of participants and personnel for possible performance bias; (4) blinding of outcome assessment for possible detection bias; (5) incomplete outcome data for possible attrition bias; (6) selective reporting for possible reporting bias; and (7) size of study for possible biases confounded by small sample size. Each category will be assigned a low, unclear, or high risk of bias and presented with a “Risk of bias” graph and “Risk of bias” summary.

3.5.3. Dealing with missing data

No pooled analysis is planned in this review. Missing data regarding concomitant drug therapy will be used to aid in the describing the landscape of trials investigating MBIs for chronic pain patients with respect to drug therapy.

4. Discussion

Chronic pain is a common and complicated health issue that has a marked negative impact on patients' quality of life, physical and mental health, relationships, and productivity.2,6 In North America, physicians have increasingly prescribed opioids for chronic pain in efforts to reduce pain intensity, despite the lack of rigorous research demonstrating its long-term effectiveness.13,18,19 Deaths from prescription opioid overdoses quadrupled in the last 15 years in the United States, with >210,000 prescription opioid-related deaths since 1999, emphasizing the need for an alternative approach to chronic pain management.1 Efforts by the government and regulatory bodies to curb the opioid crisis is unlikely to be an effective solution to the chronic pain crisis.40 The nature of attention given to the opioid crisis may worsen the stigma associated with the proper use of prescription opioids, and result in patients being aggressively tapered off prescription opioids without other treatment options to help control their pain.16 Therefore, the issue of chronic pain should be managed in a larger context than simply the opioid crisis.40 Other primary pharmacological modalities for chronic pain management include antidepressants, anticonvulsants, nonsteroidal anti-inflammatory drugs, and muscle relaxants.21 However, because of the dose-limiting adverse effects and limited efficacy of many these therapies, there is still a significant unmet need for sufferers as many patients with chronic patients are still in pain despite treatment.21,29 Furthermore, despite advancements in chronic pain research, finding a safe alternative for chronic pain remains a large challenge.29 Emerging evidence supports the safe use of MBIs in reducing pain intensity as well as improving secondary features of chronic pain.5,14,23,35 However, little is known about the current state of MBI trials with respect to concomitant drug therapy. In addition, there is no consensus regarding the clinical effects of MBIs in combination with current drug therapies for chronic pain. This review seeks to elucidate the current state of the literature and clinical effects of this combination, provide information to health care professionals on how MBIs can be integrated into patients' multidisciplinary chronic pain management strategy, and improve the quality of life of chronic pain patients. Understanding the unique effects of MBIs and its combination with drug therapy on chronic pain can also help patients formulate realistic expectations of mindfulness therapy and potentially facilitate adherence, which may help patients live productive lives despite discomfort.


The authors have no conflict of interest to declare.

This work was supported, in part, by the Queen's University Department of Anesthesiology & Perioperative Medicine, and the Chronic Pain Network of the Canadian Institutes of Health Research Strategy on Patient-Oriented Research.


[1]. Prescription opioid overdose data | drug overdose. CDC Injury Center, 2018. Available at: Accessed May 12, 2019.
[2]. Abu-Saad Huijer H. Chronic pain: a review. J Med Liban 2010;58:21–7.
[3]. Alford DP. Opioid prescribing for chronic pain—achieving the right balance through education. N Engl J Med 2016;374:301–3.
[4]. Andrew R, Derry S, Taylor RS, Straube S, Phillips CJ. The costs and consequences of adequately managed chronic non-cancer pain and chronic neuropathic pain. Pain Pract 2014;14:79–94.
[5]. Anheyer D, Haller H, Barth J, Lauche R, Dobos G, Cramer H. Mindfulness-based stress reduction for treating low back pain: a systematic review and meta-analysis. Ann Intern Med 2017;166:799–807.
[6]. Ataoglu E, Tiftik T, Kara M, Tunc H, Ersoz M, Akkus S. Effects of chronic pain on quality of life and depression in patients with spinal cord injury. Spinal Cord 2013;51:23–6.
[7]. Bishop SR, Lau M, Shapiro S, Carlson L, Anderson ND, Carmody J, Segal ZV, Abbey S, Speca M, Velting D. Mindfulness: a proposed operational definition. Clin Psychol Sci Pract 2004;11:230–41.
[8]. Borsook D. A future without chronic pain: neuroscience and clinical research. Cerebrum 2012;2012:7.
[9]. Breivik H, Collett B, Ventafridda V, Cohen R, Gallacher D. Survey of chronic pain in Europe: prevalence, impact on daily life, and treatment. Eur J Pain 2006;10:287–333.
[10]. Caudill-Slosberg MA, Schwartz LM, Woloshin S. Office visits and analgesic prescriptions for musculoskeletal pain in US: 1980 vs. 2000. PAIN 2004;109:514–19.
[11]. Cherkin DC, Sherman KJ, Balderson BH, Cook AJ, Anderson ML, Hawkes RJ, Hansen KE, Turner JA. Effect of mindfulness-based stress reduction vs cognitive behavioral therapy or usual care on back pain and functional limitations in adults with chronic low back pain: a randomized clinical trial. JAMA 2016;315:1240–9.
[12]. Cherry DK, Woodwell DA, Rechtsteiner EA. National Ambulatory Medical Care Survey: 2005 summary. Adv Data 2007:1–39.
[13]. Cheung CW, Qiu Q, Choi SW, Moore B, Goucke R, Irwin M. Chronic opioid therapy for chronic non-cancer pain: a review and comparison of treatment guidelines. Pain Physician 2014;17:401–14.
[14]. Chiesa A, Serretti A. Mindfulness-based interventions for chronic pain: a systematic review of the evidence. J Altern Complement Med 2011;17:83–93.
[15]. Chou R, Turner JA, Devine EB, Hansen RN, Sullivan SD, Blazina I, Dana T, Bougatsos C, Deyo RA. The effectiveness and risks of long-term opioid therapy for chronic pain: a systematic review for a National Institutes of Health Pathways to Prevention Workshop. Ann Intern Med 2015;162:276–86.
[16]. De Ruddere L, Craig KD. Understanding stigma and chronic pain: a-state-of-the-art review. PAIN 2016;157:1607–10.
[17]. de Souza IC, de Barros VV, Gomide HP, Miranda TC, Menezes Vde P, Kozasa EH, Noto AR. Mindfulness-based interventions for the treatment of smoking: a systematic literature review. J Altern Complement Med 2015;21:129–40.
[18]. Eccleston C, Fisher E, Thomas KH, Hearn L, Derry S, Stannard C, Knaggs R, Moore RA. Interventions for the reduction of prescribed opioid use in chronic non-cancer pain. Cochrane Database Syst Rev 2017;11:CD010323.
[19]. Frieden TR, Houry D. Reducing the risks of relief—the CDC opioid-prescribing guideline. N Engl J Med 2016;374:1501–4.
[20]. Gaskin DJ, Richard P. The economic costs of pain in the United States. J Pain 2012;13:715–24.
[21]. Gilron I, Jensen TS, Dickenson AH. Combination pharmacotherapy for management of chronic pain: from bench to bedside. Lancet Neurol 2013;12:1084–95.
[22]. Grossman P, Niemann L, Schmidt S, Walach H. Mindfulness-based stress reduction and health benefits. A meta-analysis. J Psychosom Res 2004;57:35–43.
[23]. Hilton L, Hempel S, Ewing BA, Apaydin E, Xenakis L, Newberry S, Colaiaco B, Maher AR, Shanman RM, Sorbero ME, Maglione MA. Mindfulness meditation for chronic pain: systematic review and meta-analysis. Ann Behav Med 2017;51:199–213.
[24]. Kabat-Zinn J. An outpatient program in behavioral medicine for chronic pain patients based on the practice of mindfulness meditation: theoretical considerations and preliminary results. Gen Hosp Psychiatry 1982;4:33–47.
[25]. Khoo EL, Small R, Cheng W, Hatchard T, Glynn B, Rice DB, Skidmore B, Kenny S, Hutton B, Poulin PA. Comparative evaluation of group-based mindfulness-based stress reduction and cognitive behavioural therapy for the treatment and management of chronic pain: a systematic review and network meta-analysis. Evid Based Ment Health 2019;22:26–35.
[26]. Kozasa EH, Tanaka LH, Monson C, Little S, Leao FC, Peres MP. The effects of meditation-based interventions on the treatment of fibromyalgia. Curr Pain Headache Rep 2012;16:383–7.
[27]. Lerman SF, Rudich Z, Brill S, Shalev H, Shahar G. Longitudinal associations between depression, anxiety, pain, and pain-related disability in chronic pain patients. Psychosom Med 2015;77:333–41.
[28]. Lynch ME. The need for a Canadian pain strategy. Pain Res Manag 2011;16:77–80.
[29]. Lynch ME, Watson CP. The pharmacotherapy of chronic pain: a review. Pain Res Manag 2006;11:11–38.
[30]. MacCoon DG, Imel ZE, Rosenkranz MA, Sheftel JG, Weng HY, Sullivan JC, Bonus KA, Stoney CM, Salomons TV, Davidson RJ, Lutz A. The validation of an active control intervention for Mindfulness Based Stress Reduction (MBSR). Behav Res Ther 2012;50:3–12.
[31]. Majeed MH, Ali AA, Sudak DM. Mindfulness-based interventions for chronic pain: evidence and applications. Asian J Psychiatry 2018;32:79–83.
[32]. Mars TS, Abbey H. Mindfulness meditation practise as a healthcare intervention: a systematic review. Int J Osteopathic Med 2010;13:56–66.
[33]. Moher D, Liberati A, Tetzlaff J, Altman DG. Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. Ann Intern Med 2009;151:264–9.
[34]. Nathan HJ, Poulin P, Wozny D, Taljaard M, Smyth C, Gilron I, Sorisky A, Lochnan H, Shergill Y. Randomized trial of the effect of mindfulness-based stress reduction on pain-related disability, pain intensity, health-related quality of life, and A1C in patients with painful diabetic peripheral neuropathy. Clin Diabetes 2017;35:294–304.
[35]. Reiner K, Tibi L, Lipsitz JD. Do mindfulness-based interventions reduce pain intensity? A critical review of the literature. Pain Med 2013;14:230–42.
[36]. Reitsma ML, Tranmer JE, Buchanan DM, Vandenkerkhof EG. The prevalence of chronic pain and pain-related interference in the Canadian population from 1994 to 2008. Chronic Dis Inj Can 2011;31:157–64.
[37]. Schopflocher D, Taenzer P, Jovey R. The prevalence of chronic pain in Canada. Pain Res Manag 2011;16:445–50.
[38]. Tang NK, Crane C. Suicidality in chronic pain: a review of the prevalence, risk factors and psychological links. Psychol Med 2006;36:575–86.
[39]. Tomlinson ER, Yousaf O, Vitterso AD, Jones L. Dispositional mindfulness and psychological health: a systematic review. Mindfulness 2018;9:23–43.
[40]. Waddell K, Moat K, Lavis J. Evidence brief: developing a National Pain Strategy for Canada. Hamilton: McMaster Health Forum, 2017. Available at: Accessed June 29, 2019.
[41]. Zeidan F, Grant JA, Brown CA, McHaffie JG, Coghill RC. Mindfulness meditation-related pain relief: evidence for unique brain mechanisms in the regulation of pain. Neurosci Lett 2012;520:165–73.

Chronic pain; Mindfulness; Analgesic therapy; Clinical trials; Systematic review; Meditation

Copyright © 2019 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of The International Association for the Study of Pain.