Antidepressants in the treatment for chronic low back pain: questioning the validity of meta-analyses

Objectives: To contrast the analgesic effect of duloxetine with antidepressants reported in other published randomized clinical trials (RCTs) and review articles in patients with chronic low back pain (CLBP).

Methods: In this narrative review, the results of 13 RCTs and 5 systematic reviews examining the analgesic effect of various antidepressants in CLBP were contrasted with those of 3 placebo-controlled duloxetine RCTs. Treatment effects based on the Brief Pain Inventory (BPI) average score in the duloxetine RCTs were assessed in all completers (by study and overall) and in last-observation-carried-forward (LOCF) analyses (extracted from study reports). 30%- and 50%-reduction response rates were compared between duloxetine and placebo.

Results: Eleven different antidepressants were examined in 13 individual RCTs. Sample sizes, treatment durations, and analysis methods varied across studies. Reviews each included 5 to 9 of the RCTs and came to different conclusions regarding the analgesic effect of antidepressants: 2 found no evidence while 3 reported some evidence. The completer analysis showed greater improvements in BPI average scores with duloxetine vs. placebo (significant in 2 studies). Overall, the least square mean (standard error) difference between treatments was - 0.7 (0.15) (P < 0.0001). Overall response rates were significantly larger with duloxetine than with placebo.

Conclusions: Due to the diversity of previous studies and the pooling methods used, the conclusions regarding the analgesic effect of antidepressants in CLBP drawn from systematic reviews must be interpreted with caution. Appropriately designed and powered studies similar to recently published duloxetine studies are recommended to demonstrate the analgesic effect of antidepressants.