Background: The mechanisms by which exercise and advice cause less pain and disability in patients with subacute low back pain are unknown. Objective was to estimate how much of the effect of a physiotherapist-directed exercise and advice intervention on pain and disability is mediated via changes in depressive symptoms.
Methods: Secondary causal mediation analysis of a randomized controlled trial. We measured our hypothesized mediator - depressive symptoms (Depression, Anxiety, Stress Scale-21) at 6 weeks, and the outcomes - pain (numerical rating scale) and disability (Roland Morris Disability Questionnaire) at 3 months. We pre-specified a causal model to identify potential confounders of the mediator-outcome effect and conducted a sensitivity analysis to assess the robustness of the Average Causal Mediation Effect (ACME) under varying levels of unknown confounding. 
Results: Data from 240 patients were analyzed (average age 50.5 (SD 15.6) years, 52% male, median depression score 4). Exercise combined with advice had a significant effect on pain (-1.19, 95%CI -1.85 to -0.48), and disability (-1.70, 95%CI -2.89 to -0.57), but this effect was not mediated via depressive symptoms: ACME on pain (0.05, 95%CI -0.24 to 0.15), ACME on disability (-0.10, 95%CI -0.59 to 0.38). 
Conclusions: Depressive symptoms did not mediate the effect of exercise and/or advice in this population. However, depressive symptoms were associated with pain and disability.

DO CHANGES IN DEPRESSIVE SYMPTOMS MEDIATE THE EFFECT OF EXERCISE AND ADVICE FOR SUBACUTE LOW BACK PAIN?