Eur Spine J DOI 10.1007/s00586-015-3891-4 REVIEW ARTICLE Are non-steroidal anti-inflammatory drugs effective for the management of neck pain and associated disorders, whiplash-associated disorders, or non-specific low back pain? A systematic review of systematic reviews by the Ontario Protocol for Traffic Injury Management (OPTIMa) Collaboration 1,2,3 1,4 5 1,6 Jessica J. Wong • Pierre Coˆte´ • Arthur Ameis • Sharanya Varatharajan • 1,7 1,6 8,9 Thepikaa Varatharajan • Heather M. Shearer • Robert J. Brison • 1,6 1,6 1,6 1,10 Deborah Sutton • Kristi Randhawa • Hainan Yu • Danielle Southerst • 4 4,6 1 11 Rachel Goldgrub • Silvano Mior • Maja Stupar • Linda J. Carroll • Anne Taylor-Vaisey1 Received: 5 November 2014 / Revised: 18 March 2015 / Accepted: 19 March 2015 Ó Springer-Verlag Berlin Heidelberg 2015 Abstract included systematic reviews with a low risk of bias in our Purpose To evaluate the effectiveness of non-steroidal best evidence synthesis. anti-inflammatory drugs (NSAIDs) for the management of Results We screened 706 citations and 14 systematic re- neck pain and associated disorders (NAD), whiplash-as- views were eligible for critical appraisal. Eight systematic sociated disorders, and non-specific low back pain (LBP) reviews had a low risk of bias. For recent-onset NAD, with or without radiculopathy. evidence suggests that intramuscular NSAIDs lead to Methods We systematically searched six databases from similar outcomes as combined manipulation and soft tissue 2000 to 2014. Random pairs of independent reviewers therapy. For NAD (duration not specified), oral NSAIDs critically appraised eligible systematic reviews using the may be more effective than placebo. For recent-onset LBP, Scottish Intercollegiate Guidelines Network criteria. We evidence suggests that: (1) oral NSAIDs lead to similar outcomes to placebo or a muscle relaxant; and (2) oral NSAIDs with bed rest lead to similar outcomes as placebo Systematic Review Registration Number: CRD42014009782. & Jessica J. Wong 6 Graduate Education and Research Programs, Canadian [email protected] Memorial Chiropractic College (CMCC), 6100 Leslie Street, Toronto, ON M2H 3J1, Canada 1 UOIT-CMCC Centre for the Study of Disability Prevention 7 and Rehabilitation, University of Ontario Institute of Graduate Studies in Masters of Public Health, University of Technology (UOIT) and Canadian Memorial Chiropractic Saskatchewan, 104 Clinic Place, Saskatoon, SK S7N 5E5, College (CMCC), 6100 Leslie Street, Toronto, ON M2H 3J1, Canada Canada 8 Kingston General Hospital, 76 Stuart Street, Kingston, 2 Undergraduate Education, Canadian Memorial Chiropractic ON K7L 2V7, Canada College, 6100 Leslie Street, Toronto, ON M2H 3J1, Canada 9 Department of Emergency Medicine, School of Medicine, 3 Division of Graduate Studies, Canadian Memorial Queen’s University, Kingston, ON, Canada Chiropractic College, 6100 Leslie Street, Toronto, 10 Rebecca MacDonald Centre for Arthritis and Autoimmune ON M2H 3J1, Canada Disease, Mount Sinai Hospital, Joseph and Wolf Lebovic 4 Faculty of Health Sciences, University of Ontario Institute of Health Complex, 60 Murray Street, 2nd Floor (Main), Technology (UOIT), 2000 Simcoe Street North, Oshawa, Toronto, ON M5T 3L9, Canada ON L1H 7L7, Canada 11 Injury Prevention Centre, University of Alberta, 4075 RTF, 5 Certification Program in Insurance Medicine and Medico- 8308 114 Street, Edmonton T6G 2E1, AB, Canada legal Expertise, Faculty of Medicine, University of Montreal, N-414, Roger-Gaudry Building, 2900, Boulevard Edouard- Montpetit, Montreal, QC H3T 1J4, Canada 123 Eur Spine J with bed rest. For persistent LBP, evidence suggests that: low back pain [25, 26]. For lumbar radiculopathy, two (1) oral NSAIDs are more effective than placebo; and (2) systematic reviews reported that NSAIDs are not more oral NSAIDs may be more effective than acetaminophen. effective than placebo [27, 28]. For recent-onset LBP with radiculopathy, there is incon- Different methodologies used to conduct the previous sistent evidence on the effectiveness of oral NSAIDs versus reviews likely contributed to the differences in their con- placebo. Finally, different oral NSAIDs lead to similar clusions. The methodologies differed in the application of outcomes for neck and LBP with or without radiculopathy. critical appraisal and evidence synthesis methods. Across Conclusions For NAD, oral NSAIDs may be more ef- reviews, different instruments were used to critically ap- fective than placebo. Oral NSAIDs are more effective than praise the literature and synthesize the evidence [21–28]. placebo for persistent LBP, but not for recent-onset LBP. Inclusion of studies with a high risk of bias may threaten Different oral NSAIDs lead to similar outcomes for neck the internal validity of a systematic review. Randomized pain and LBP. controlled trials (RCTs) with poor internal validity were used in the evidence synthesis of six reviews [21, 25, 26, Keywords Whiplash-associated disorders Á Neck pain 29–31]. Considering the varying methodologies used in and associated disorders Á Nonspecific low back pain Á previous systematic reviews, an in-depth review of their Nonsteroidal anti-inflammatory drugs Á Systematic review Á quality is warranted prior to accepting their results. Medication We conducted a systematic review of systematic re- views to examine the effectiveness of NSAIDs for the management of neck pain and associated disorders (NAD), Introduction whiplash-associated disorders (WAD), or non-specific low back pain with or without radiculopathy. Neck and back pain are experienced by more than 80 % of the population during their lifetime, and are common rea- sons for seeking healthcare [1–6]. These conditions are Methods costly, and work absenteeism and lost productivity are frequent complications [7–9]. Most neck and back pain are Registration common sources of disability, whether attributed to work, traffic collision, or daily activities [1, 3, 10–13]. To date, We registered our protocol with the International few interventions demonstrate efficacy on a scientifically Prospective Register of Systematic Reviews (PROSPERO) valid basis and most interventions are only associated with on May 14, 2014 (CRD42014009782). short-term benefits [14, 15]. Non-steroidal anti-inflammatory drugs (NSAIDs) are Eligibility criteria commonly used for neck and low back pain. NSAIDs suppress inflammatory processes that produce swelling and Population pain [16]. In the United States, NSAIDs are the most common intervention prescribed for non-malignant chronic Our review targeted systematic reviews of adults or chil- pain, including musculoskeletal disorders, with use re- dren with NAD or WAD (grades I–III), or non-specific low ported in approximately 95 % of visits to physicians [17]. back pain (with or without radiculopathy) and excluded In the United Kingdom, general practitioners prescribed pain from major pathology (fractures, dislocations, spinal NSAIDs to approximately 30 % of patients with chronic cord injury, infection, neoplasms, systemic disease). We low back pain [18]. In Spain, 41 % of patients with low defined NAD and WAD according to previous classifica- back pain reported taking NSAIDs for more than 1 month tions [32, 33] (Table 1). We defined non-specific low back in the past year [19]. pain as low back pain with or without radiculopathy in the Despite its common use, the effectiveness of NSAIDs absence of specific pathological entities [24]. for the management of neck and low back pain is not firmly established [20–22]. Several systematic reviews examining Intervention NSAIDs for neck and low back pain have reported limited or unclear evidence [20–22]. In contrast, two systematic We restricted our review to systematic reviews that tested reviews concluded (based on low quality evidence and the effectiveness of NSAIDs. NSAIDs are defined as small effect sizes) that NSAIDs are effective for short-term medications that block the action of cyclo-oxygenase symptomatic relief in patients with low back pain [23, 24]. (Cox)-1 and/or Cox-2 (necessary for prostaglandin pro- Furthermore, two reviews found evidence supporting the duction), thus reducing inflammation and pain [16]. Cox-1 use of NSAIDs in individuals with acute [25] or chronic enzymes are also cyto-protective; blocking their action is 123 Eur Spine J Table 1 Classification of grades for neck pain and associated dis- systematic review of studies (with or without meta-analy- orders [32] and whiplash-associated disorders [33] sis); and (4) adults or children with NAD, WAD, or non- Grade Definition specific low back pain with or without radiculopathy (mixed populations must have stratified results for NAD, Neck pain and associated disorders WAD, or non-specific low back pain). I No signs or symptoms suggestive of major structural We excluded: (1) guidelines, letters, editorials, com- pathology and no or minor interference with activities of daily living mentaries, unpublished manuscripts, dissertations, govern- II No signs or symptoms of major structural pathology, ment reports, books, conference proceedings, meeting but major interference with activities of daily living abstracts, lectures and addresses, consensus development III No signs or symptoms of major structural pathology, but statements; (2) non-systematic reviews, RCTs, cohort presence of neurologic signs such as decreased deep tendon studies, case–control studies, cross-sectional studies, case reflexes, weakness or sensory deficits reports/series, qualitative studies, biomechanical studies, a IV Signs or symptoms of major