1. 2013;16;E685-E704Drug Therapy for the Treatment of Chronic Nonspecific Low Back Pain: Systematic Review and Meta-analysis
   Systematic Review
   Joanne WY Chung, PhD, Yingchun Zeng, MPhil, and Thomas KS Wong, PhD.

BACKGROUND: Low back pain (LBP) is one of the most common health problems in adults. The impact of LBP on the individual can cause loss of health status in the form of symptoms and loss of function related to pain in the back; limitation of daily, leisure, and/or strenuous activities, and disability. LBP also poses an economic burden to society, mainly in terms of one of the most common reasons for seeking medical care (direct treatment costs), and accounts for the large number of work days lost (indirect costs). To reduce the impact of LBP on adults, drug therapy is the most frequently recommended intervention. Over the last decade, a substantial number of randomized clinical trials of drug therapy for LBP have been published.

OBJECTIVE: To determine the effectiveness of drug therapy for the treatment of chronic nonspecific low back pain (CNLBP).

STUDY DESIGN: Systematic review

METHODS: A systematic review and meta-analysis of randomized controlled trials was conducted. Five databases (Medline, CINAHL, Science Direct, CAJ Full-text Database, and Cochrane databases) were searched for articles published from 2002 to 2012. The eligibility criteria were randomized trials and double-blind controlled trials of oral or injection drug therapy for CNLBP in subjects who were aged at least 18 years old, published in English or Chinese. Two independent reviewers extracted the data. 

RESULTS: A total of 25 drug therapy trials were included. cyclo-oxygenase-2 (COX-2) nonsteroidal anti-inflammatory drugs (NSAIDs), tramadol, and opioids were commonly used. Only 5 trials studied the efficacy of adjuvant analgesics of antiepileptics (n = 1) and antidepressants (n = 4) for CNLBP. The standardized mean difference (SMD) for COX-2 NSAIDs in pain relief was -12.03 (95% confidence interval [CI]: -15.00 to -9.06). The SMD for tramadol in pain relief was -1.72 (95% CI: -3.45 to 0.01). As the 95% CI crossed 0, this effect size was not considered statistically significant. The SMD for the overall effects of opioids in pain relief was -5.18 (95% CI: -8.30 to -2.05). The SMD for the partial opioid agonist drug in pain relief was -7.46 (95% CI: -11.87 to -3.04).

LIMITATIONS: The follow-up periods of these included trials in the meta-analysis ranged from 4 to 24 weeks. The difference of follow-up periods influenced how study outcomes were recorded. These included trials also had significant differences in patient selections. Some trials may actually include CNLBP patients with neuropathic pain, as not having focal neurological findings or signs does not mean that the pain is not neuropathic. Consequently, different pain conditions may influence patients who responded to the same drug and then influence pooled estimates of treatment effect size.

CONCLUSION: This review endorses the use of COX-2 NSAIDs as the first-line drugs for CNLBP. Tramadol shows no statistically significant effect on pain relief, but has small effect sizes in improving functioning. Among included opioid therapy studies, the overall effects of opioids and the partial opioids agonist drug had statistically significant treatment effects in pain relief for CNLBP patients.