This chapter focuses on pharmacological approaches to chronic low-back pain (CLBP). In CLBP, one of the major issues for the ED caregiver is use of opioids. The utility of opioids in CLBP is limited not only by their marginal analgesic efficacy, but also by the risk of addictive behavior. Although studies of truly CLBP are lacking, it is reasonable to use NSAIDs provided that potential side effects risks are incorporated into therapeutic decision-making. Some authors recommend avoiding the potential cardiovascular risk with COX-2 selective NSAIDs by instead prescribing dual therapy with a non-selective NSAID and a proton pump inhibitor. A 2003 meta-analysis found five RCTs demonstrating some CLBP relief with cyclic anti-depressants. The benefits of these cyclic anti-depressants are independent of their anti-depressant effects, since studies demonstrating the agents' efficacy excluded patients with clinical depression.