Evaluation of the effect of insulin sensitivity-enhancing lifestyle- and dietary-related adjuncts on antidepressant treatment response: A systematic review and meta-analysis

Depression is associated with insulin resistance (IR). However, the potential beneficial effect, on antidepressant treatment response, of adjunctive therapy with insulin sensitivity-enhancing lifestyle and dietary interventions (exercise; supplementation with: vitamin D, magnesium, zinc, probiotics or omega-3 fatty acids) has not been systematically explored. To determine the effect of the above stated adjuncts on antidepressant treatment response in clinically depressed patients via a systematic review and meta-analysis. RCTs which assessed the effect, on antidepressant treatment response of adjunctive therapy with any of the interventions in comparison with treatment as usual were included. The interventions had a significant antidepressant effect, with SMD for follow-up (end of study) scores and change (from baseline) scores being -0.88, [95% CI: -1.19 to -0.57; P < 0.001] and -1.98 [95% CI -2.86 to -1.10; P < 0.001], respectively. The odds ratio (OR) for remission was 2.28 (95% CI 1.42 to 3.66; P < 0.001). The number-needed-to-treat (NNT) for remission was 6. Subgroup analysis of the follow-up scores revealed age effect: SMD significant in those with mean age ≤50 (-1.02 SMD; 95% CI: -1.40 to -0.64; p < 0.001) and insignificant in those with mean age >50 (-0.38 SMD (95% CI: -0.82 to 0.05; P = 0.08)). Also, the interventions were more beneficial among outpatients- SMD: -0.97 (95% CI: -1.32 to -0.62; P < 0.001) compared to inpatients- SMD: -0.34 (95% CI: -0.88 to 0.20; P = 0.22). Sensitivity analysis did not change the results. The finding that antidepressant treatment response may be improved using insulin sensitivity-enhancing lifestyle and dietary adjuncts is worthy of further exploration. Psychiatry; Biological Psychiatry; Depression; Pharmacology; Endocrinology; Endocrine System; depression; Adjuncts; Insulin sensitivity; Lifestyle; Dietary Supplements; Antidepressants; systematic review.