Study design: Systematic review of the literature with subgroup analysis for heterogeneous treatment effects.
Objective: The objectives of this systematic review were to summarize prior Cochrane reports regarding the safety and effectiveness of opioids, nonsteroidal anti-inflammatory drugs (NSAIDs), and antidepressants for treatment of chronic low back pain (LBP) and to evaluate whether certain subpopulations respond more favorably to pharmacological management.
Summary of background data: While medications are a mainstay of LBP management, there is uncertainty as to the optimal use of commonly prescribed medications such as opioids, antidepressants, and NSAIDS.
Methods: To summarize the overall treatment effect and safety for each of the three pharmacological drug classes (opioids, NSAIDs, or antidepressants), we summarized existing Cochrane reviews. To evaluate whether the effects of treatment varied by specific subgroups of patients, we sought randomized controlled trials (RCTs) evaluating one of the three pharmacological drug classes versus an alternative management for chronic LBP.
Results: Based on the Cochrane reviews, opioids are more effective than placebo with respect to pain and disability, with a much greater effect size for pain than disability. When compared with NSAIDs, opioids did not confer a greater benefit with regard to pain and disability. The rate of side effects from opioids is significantly greater than placebo with differences ranging between 2% and 9%. The systematic review of RCTs showed that antidepressants are not more effective than placebo with respect to pain, functional status, or depression. Certain subgroup treatment effects were identified, supporting our hypothesis that chronic LBP should be considered a heterogeneous set of disorders. As such, chronic LBP subgroups should be considered both when making clinical treatment decisions and when designing future research trials.
Conclusion: Opioids and NSAIDs are effective for chronic LBP, while antidepressants have no meaningful clinical benefit. Based on the significant rate of side effects with opioids and the lack of convincing superiority over NSAIDs, opioids are not recommended as a treatment for chronic LBP. Attention to subgroups of patients will likely help guide treatment, and will likely help increase the clinical impact of future research.
Clinical recommendations: Recommendation 1: NSAIDs should be considered as a treatment of chronic LBP (Strength: Strong). There is evidence demonstrating favorable effectiveness, but also significant side effects that may have meaningful clinical consequences. Recommendation 2: Opioids may be considered in the treatment of chronic LBP but should be avoided if possible (Strength: Weak). There is evidence demonstrating favorable effectiveness compared to placebo, similar effectiveness compared to NSAIDs, and with significant side effects including decreasing effectiveness related to habituation when used long-term. Recommendation 3: Antidepressants should not be routinely used for the treatment of chronic LBP (Strength: Strong). There is evidence that they are not more effective than placebo with respect to pain, functional status, or depression. Based on the hypothesis that chronic LBP is a symptom reflective of a heterogeneous group of disorders, categorization of certain patient specific subgroups may be helpful in guiding future treatment decision making. It is likely that inclusion of subgroup factors in future RCTs will provide information needed to improve the strength and specificity of future clinical recommendations.