Medications for Acute and Chronic Low Back Pain: A Review of the Evidence for an American Pain Society/American College of Physicians Clinical Practice Guideline

In the United States, low back pain is the fifth most common reason for all physician office visits and the second most common symptomatic reason (1, 2). Medications are the most frequently recommended intervention for low back pain (1, 3). In 1 study, 80% of primary care patients with low back pain were prescribed at least 1 medication at their initial office visit, and more than one third were prescribed 2 or more drugs (4). The most commonly prescribed medications for low back pain are nonsteroidal anti-inflammatory drugs (NSAIDs), skeletal muscle relaxants, and opioid analgesics (47). Benzodiazepines, systemic corticosteroids, antidepressant medications, and antiepileptic drugs are also prescribed (8). Frequently used over-the-counter medications include acetaminophen, aspirin, and certain NSAIDs. A challenge in choosing pharmacologic therapy for low back pain is that each class of medication is associated with a unique balance of benefits and harms. In addition, benefits and harms may vary for individual drugs within a medication class. Previous reviews found only limited evidence to support use of most medications for low back pain. For example, a systematic review published in 1996 found insufficient evidence to support use of any medication for low back pain other than NSAIDs (good evidence) and skeletal muscle relaxants (fair evidence) (9). This article reviews current evidence on benefits and harms of medications for acute and chronic low back pain. It is part of a larger evidence review commissioned by the American Pain Society and the American College of Physicians to guide recommendations for management of low back pain (10). Methods Data Sources and Searches An expert panel convened by the American Pain Society and the American College of Physicians determined which medications would be included in this review. The panel chose acetaminophen, NSAIDs (nonselective, cyclooxygenase-2 selective, and aspirin), antidepressants, benzodiazepines, antiepileptic drugs, skeletal muscle relaxants, opioid analgesics, tramadol, and systemic corticosteroids. We searched MEDLINE (1966 through November 2006) and the Cochrane Database of Systematic Reviews (2006, Issue 4) for relevant systematic reviews, combining terms for low back pain with a search strategy for identifying systematic reviews. When higher-quality systematic reviews were not available for a particular medication, we conducted additional searches for primary studies (combining terms for low back pain with the medication of interest) on MEDLINE and the Cochrane Central Register of Controlled Trials. Full details of the search strategies are available in the complete evidence report (10). Electronic searches were supplemented by hand searching of reference lists and additional citations suggested by experts. We did not include trials published only as conference abstracts. Evidence Selection We included all randomized, controlled trials that met all of the following criteria: 1) reported in the English language, or in a non-English language but included in an English-language systematic review; 2) evaluated nonpregnant adults (>18 years of age) with low back pain (alone or with leg pain) of any duration; 3) evaluated a target medication, either alone or in addition to another target medication (dual therapy); and 4) reported at least 1 of the following outcomes: back-specific function, generic health status, pain, work disability, or patient satisfaction (11, 12). We excluded trials that compared dual-medication therapy with therapy using a different medication, medication combination, or placebo. We also excluded trials of low back pain associated with acute major trauma, cancer, infection, the cauda equina syndrome, fibromyalgia, and osteoporosis or vertebral compression fracture. Because of the large number of trials evaluating medications for low back pain, our primary source for trials was systematic reviews. When multiple systematic reviews were available for a target medication, we excluded outdated systematic reviews, which we defined as systematic reviews with a published update, or systematic reviews published before 2000. When a higher-quality systematic review was not available for a particular intervention, we included all relevant randomized, controlled trials. Data Extraction and Quality Assessment For each included systematic review, we abstracted information on search methods; inclusion criteria; methods for rating study quality; characteristics of included studies; methods for synthesizing data; and results, including the number and quality of trials for each comparison and outcome in patients with acute (<4 weeks' duration) low back pain, chronic/subacute (>4 weeks' duration) low back pain, and back pain with sciatica. If specific data on duration of trials were not provided, we relied on the categorization (acute or chronic/subacute) assigned by the systematic review. For each trial not included in a systematic review, we abstracted information on study design, participant characteristics, interventions, and results. We considered mean improvements of 5 to 10 points on a 100-point visual analogue pain scale (or equivalent) to be small or slight; 10 to 20 points, moderate; and more than 20 points, large or substantial. For back-specific functional status, we classified mean improvements of 2 to 5 points on the RolandMorris Disability Questionnaire (scale, 0 to 24) and 10 to 20 points on the Oswestry Disability Index (scale, 0 to 100) as moderate (13). We also considered standardized mean differences of 0.2 to 0.5 to be small or slight; 0.5 to 0.8, moderate; and greater than 0.8, large (14). Some evidence suggests that our classification of mean improvements and standardized mean differences for pain and functional status are roughly concordant in patients with low back pain (1520). Because few trials reported the proportion of patients meeting specific thresholds (such as >30% reduction in pain score) for target outcomes, it was usually not possible to report numbers needed to treat for benefit. When those were reported, we considered a relative risk (RR) of 1.25 to 2.00 for the proportion of patients reporting greater than 30% pain relief (or a similar outcome) to indicate a moderate benefit. Two reviewers independently rated the quality of each included trial. Discrepancies were resolved through joint review and a consensus process. We assessed internal validity (quality) of systematic reviews by using the Oxman criteria (Appendix Table 1) (21, 22). According to this system, systematic reviews receiving a score of 4 or less (on a scale of 1 to 7) have potential major flaws and are more likely to produce positive conclusions about effectiveness of interventions (22, 23). We classified such systematic reviews as lower quality; those receiving scores of 5 or more were graded as higher quality. Appendix Table 1. Quality Rating System for Systematic Reviews We did not abstract results of individual trials if they were included in a higher-quality systematic review. Instead, we relied on results and quality ratings for the trials as reported by the systematic reviews. We considered trials receiving more than half of the maximum possible quality score to be higher quality for any quality rating system used (24, 25). We assessed internal validity of randomized clinical trials not included in a higher-quality systematic review by using the criteria of the Cochrane Back Review Group (Appendix Table 2) (26). We considered trials receiving more than half of the total possible score (6 of a maximum 11) higher quality and those receiving less than half lower quality (24, 25). Appendix Table 2. Quality Rating System for Randomized, Controlled Trials Data Synthesis We assessed overall strength of evidence for a body of evidence by using methods adapted from the U.S. Preventive Services Task Force (27). To assign an overall strength of evidence (good, fair, or poor), we considered the number, quality, and size of studies; consistency of results among studies; and directness of evidence. Minimum criteria for fair- and good-quality ratings are shown in Appendix Table 3. Appendix Table 3. Methods for Grading the Overall Strength of the Evidence for an Intervention Consistent results from many higher-quality studies across a broad range of populations support a high degree of certainty that the results of the studies are true (the entire body of evidence would be considered good quality). For a fair-quality body of evidence, results could be due to true effects or to biases operating across some or all of the studies. For a poor-quality body of evidence, any conclusion is uncertain. To evaluate consistency, we classified conclusions of trials and systematic reviews as positive (the medication is beneficial), negative (the medication is harmful or not beneficial), or uncertain (the estimates are imprecise, the evidence unclear, or the results inconsistent) (22). We defined inconsistency as greater than 25% of trials reaching discordant conclusions (positive vs. negative), 2 or more higher-quality systematic reviews reaching discordant conclusions, or unexplained heterogeneity (for pooled data). Role of the Funding Source The funding source had no role in the design, conduct, or reporting of this review or in the decision to publish the manuscript. Results Literature Reviewed We reviewed 1292 abstracts identified by searches for systematic reviews. Of these, 21 appeared potentially relevant and were retrieved. We excluded 7 outdated reviews of NSAIDs (28), antidepressants (2931), and multiple drugs (9, 32, 33) (Appendix Table 4). We also excluded 3 reviews that did not clearly use systematic methods (3436) and 4 systematic reviews that evaluated target medications but did not report results specifically for patients with low back pain (3739). We included 7 systematic reviews (Appendix Table 5) of NSAIDs (40, 41), antidepressants (42, 43), skeletal mus