January 25, 2008 — A review of the literature on drug relief for low back pain (LBP) suggests that the popular nonsteroidal anti-inflammatory drugs (NSAIDs) are no more effective than other drugs such as acetaminophen, narcotic analgesics, and muscle relaxants.
The review, published in the January 23 online issue of Cochrane Database of Systematic Reviews, also found that NSAIDs had more adverse effects than placebo and acetaminophen but fewer effects than muscle relaxants and narcotic analgesics. In addition, evidence from the review suggests that no one NSAID is clearly more effective than another.
The review should spark debate among clinicians and policy makers who develop clinical guidelines, Pepijn Roelofs, a doctoral student at the Erasmus University Medical Centre in Rotterdam, the Netherlands, and lead reviewer, told Medscape Neurology and Neurosurgery.
“The results of this study support those guidelines for the management of acute LBP in primary care that recommend NSAIDs as a treatment option after paracetamol (the European version of Tylenol or acetaminophen) has been tried, since there are fewer side effects with paracetamol.”
Most Prescribed Medication Worldwide
NSAIDs are the most frequently prescribed medication worldwide, the review authors note. Current guidelines recommend the prescription of an NSAID as an option for symptomatic relief in the management of LBP. Most guidelines recommend NSAIDs as a treatment option after paracetamol has been tried. Goals for NSAID therapy include symptomatic relief and facilitation of early return to normal activities.
For this Cochrane review, researchers carried out searches of various databases, including MEDLINE (1966 – June 2007) and EMBASE (1988 – June 2007) for studies in English, German, and Dutch. Studies were assessed for methodologic criteria and clinical relevance before a final set of 65 studies (59 English and 6 German) that included 11,237 patients was selected. Of these studies, 28 (42%) were considered high quality.
Studies included in the review involved 1 or more types of NSAID. They included comparisons of NSAIDs with the following groups:
- Other drugs (eg, narcotic analgesics or muscle relaxants)
- Another NSAID (eg, traditional drugs vs selective cyclooxygenase-2 [COX-2] inhibitors)
- Another NSAID plus a muscle relaxant
- Another NSAID plus B vitamin
- Nondrug treatment
The studies were randomized controlled trials (RCTs; double-blind, single-blind, and open label) as well as double-blind controlled trials. Subjects in the studies were 18 years or older who had nonspecific LBP with or without sciatica. The review excluded studies that enrolled subjects with back pain caused by infection, neoplasm, metastasis, osteoporosis, rheumatoid arthritis, or fractures.
Outcome measures for the studies included the following:
- Pain intensity (eg, Visual Analog Scale or Numerical Rating Scale)
- Global measure (eg, overall improvement, proportion of patients recovered)
- Back pain functional status
- Return-to-work status
- Adverse effects
The review found moderate evidence that NSAIDs are not much more effective than other drugs for acute LBP and have more adverse effects than paracetamol. “This review suggests that NSAIDs are effective for short term global improvement in patients with acute and chronic LBP without sciatica, although the effects are small,” said Dr. Roelofs.
Individual NSAIDs Equally Effective
The review also uncovered strong evidence that various types of NSAIDs, including the selective COX-2 inhibitors, are equally effective for acute LBP. It showed as well that COX-2 inhibitors had statistically significant fewer adverse effects than traditional NSAIDs.
The long-term use of NSAIDs is controversial because of cardiovascular adverse effects in patients with cardiovascular risk factors such as previous angina pectoris, heart failure, or myocardial infarction, said Dr. Roelofs. Well-designed studies evaluating these risks are lacking, he believes. “For patients without cardiovascular risk factors, probably the benefits of short term use of NSAIDs outweigh their potential cardiovascular adverse effects,” he said, although the decision as to which drug to prescribe should be a clinical decision made between the clinician and the patient based on individual circumstances.
An area for future research will likely be adverse effects of NSAIDs and pain involving sciatica, said Dr. Roelofs.
The study was supported by the Dutch Health Insurance Board. One of the review authors is a coordinating editor, and another review author is an editor with the Cochrane Back Review Group. Editors are required to conduct at least 1 Cochrane review. This requirement ensures that editors are aware of the processes and commitment needed to conduct reviews. This involvement does not seem to be a source of conflict of interest in the Cochrane Back Review Group. Any editor who is a review author is excluded from editorial decisions on the review in which they are contributors. The remaining review authors have disclosed no relevant financial relationships.
Cochrane Database Syst Rev. Published online January 23, 2008.
Learning Objectives for This Educational Activity
Upon completion of this activity, participants will be able to:
- Compare the efficacy of nonsteroidal anti-inflammatory drugs vs other treatment in low back pain.
- Compare the safety of nonsteroidal anti-inflammatory drugs vs other treatment in low back pain.
LBP is a major health problem in western industrialized countries, causing significant disability, morbidity, and healthcare expenditures. Although it usually improves spontaneously, LBP is often treated with NSAIDs, which are the most frequently prescribed medications throughout the world. Despite the underlying rationale for use of NSAIDs based on their analgesic and anti-inflammatory properties, evidence of efficacy in LBP is not clearly established.
Guidelines for the management of LBP in primary care settings recommend NSAIDs as a therapeutic option for symptomatic relief. Compared with nonselective NSAIDs, selective COX-2 inhibitors have a lower risk for gastrointestinal tract adverse effects, but there have been concerns regarding their cardiovascular safety. The present Cochrane review summarizes the available evidence regarding both traditional NSAIDs and selective COX-2 inhibitors in the management of LBP.
- The objective of this review was to evaluate the effects of NSAIDs and COX-2 inhibitors in the management of nonspecific LBP and to determine what NSAID is most effective.
- The investigators searched MEDLINE, EMBASE, and the Cochrane Central Register of Controlled Trials through June 2007 and screened references from relevant reviews and trial reports.
- Inclusion criteria for reviewed studies were RCTs and double-blind RCTs of NSAIDs in nonspecific LBP with or without sciatica, reported in English, Dutch, or German.
- Comparisons of NSAIDs with reference treatments that were reviewed were NSAIDs vs placebo; NSAIDs vs acetaminophen/paracetamol; NSAIDs vs other drugs, such as narcotic analgesics or muscle relaxants; traditional NSAIDs vs other NSAIDs such as selective COX-2 inhibitors; NSAIDs vs NSAIDs plus muscle relaxant; NSAIDs vs NSAIDs plus B vitamins; and NSAIDs vs nondrug treatment.
- 2 reviewers independently extracted data and evaluated methodologic quality and clinical relevance of the studies.
- Meta-analysis was performed when data were considered clinically homogeneous.
- If data were lacking for clinically homogeneous trials, the reviewers used a rating system with 4 levels of evidence (strong, moderate, limited, no evidence) for qualitative analysis.
- This review included 65 trials enrolling a total of 11,237 patients.
- Only 42% of the studies were considered to be of high quality. Limitations of the included studies were small sample size limiting statistical power, relatively short follow-up, and few data on long-term efficacy and safety.
- All newly added studies evaluating NSAIDs for chronic LBP used a “flare design” in which patients who were already responding well to NSAIDs were only included when they had a large worsening in LBP complaints during a wash-out period. This may have overestimated the efficacy and underestimated the adverse effects, and it decreases the external validity for daily practice.
- Quantitative analysis, in which the results of individual RCTs were statistically pooled, showed statistically significant effects favoring NSAIDs vs placebo for populations with acute and chronic LBP without sciatica.
- Compared with placebo, NSAIDs had statistically significantly more adverse effects.
- For patients with acute LBP, the NSAIDs group used fewer additional analgesics vs the placebo group.
- Evidence was moderate that NSAIDs were not more effective than paracetamol/acetaminophen for acute LBP, and paracetamol/acetaminophen had fewer adverse effects.
- Evidence was moderate that NSAIDs are not more effective than other drugs for acute LBP, including paracetamol/acetaminophen, narcotic analgesics, and muscle relaxants.
- NSAIDs were associated with fewer adverse effects vs muscle relaxants and narcotic analgesics.
- Evidence was strong that various types of NSAIDs, including COX-2 inhibitors, are equally effective for acute LBP, but COX-2 inhibitors were associated with statistically significantly fewer adverse effects than traditional NSAIDs, particularly stomach ulcers.
- Recent studies have shown increased cardiovascular risks in specific patient groups treated with COX-2 inhibitors.
- Based on this review, the authors concluded that NSAIDs are effective for short-term symptomatic relief in patients with acute and chronic LBP without sciatica, but effect sizes are small, and no specific type of NSAID is clearly more effective than other types.
- For acute LBP, evidence is conflicting that NSAIDs are more effective than simple analgesics or bed rest, and moderate NSAIDs are not more effective than other drugs, physiotherapy, or spinal manipulation.
Pearls for Practice
- A Cochrane review suggests that NSAIDs are effective for short-term symptomatic relief in patients with acute and chronic LBP without sciatica, but effect sizes are small. No specific type of NSAID is clearly more effective than other types.
- Although the selective COX-2 inhibitors had fewer adverse effects vs the traditional NSAIDs in the RCTs included in this review, recent studies have shown that COX-2 inhibitors are associated with increased cardiovascular risks in specific patient populations.