Background: Back pain is one of the most common problems in primary care. Antidepressant medication is often prescribed, especially for chronic back discomfort, to alleviate pain and restore the patient's ability to conduct activities of daily living. Objective: To assess the efficacy of antidepressants in treating back pain in adults. Methods: We searched the MEDLINE (1966-2000), Psyc-Lit, Cinhal, EMBASE, AIDSLINE, HealthSTAR, CANCERLIT, the Cochrane Library (clinical trials registry and the Database of Systematic Reviews), Micromedex, and Federal Research in Progress databases and references of reviewed articles. Included articles were written in English and dealt with randomized placebo-controlled trials of antidepressant medication use among adults with chronic back pain. Two reviewers abstracted data independently. Two continuous outcomes, change in back pain severity and ability to perform activities of daily living, were measured. Study quality was assessed with the methods used by Jadad and colleagues, and data were synthesized using a random-effects model. Results: Nine randomized controlled trials with 10 treatment arms and 504 patients were included. Seven treatment arms included patients with major depression. Patients had chronic back pain, averaging 10.4 years. Patients treated with antidepressants were more likely to improve in pain severity than those taking placebo (standardized mean difference, 0.41; 95% confidence interval, 0.22-0.61) but not in activities of daily living (standardized mean difference, 0.24; 95% confidence interval, -0.21-0.69). Patients treated with antidepressants experienced more adverse effects (22% vs 14%, P=.01) than those receiving placebo. Conclusion: Antidepressants are more effective than placebo in reducing pain severity but not functional status in chronic back pain.