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


Depression is the leading cause of disability worldwide and is known to be associated with insulin resistance (IR). Insulin resistance worsens the symptoms of depression and reduces the effectiveness of antidepressant medications in some depressed patients. Many studies have assessed the effect of adjunctive exercise, vitamin D supplementation, zinc supplementation, magnesium, probiotics, unsaturated fatty acids, and hygienic-dietary recommendations (sleep hygiene, healthy diet, physical activity, and sunlight exposure, combined or singly used), individually, on antidepressant treatment response. However, despite the reported insulin sensitivity-enhancing potential of these adjuncts, no systematic review has collectively analysed their antidepressant effect with regards to insulin sensitivity.


In this systematic review, we will analyse the effect of the above-stated adjuncts on antidepressant treatment response (primary outcome) in comparison with treatment as usual with or without adjunctive placebo after identifying the relevant trials from a systematic literature search. Randomised controlled trials involving clinically depressed patients with diagnosis of major depressive, dysthymic or bipolar disorder will be considered. Changes in insulin sensitivity parameters, following treatment, will also be analysed as the secondary outcome. Effect estimates of the included trials will be combined using random-effects meta-analysis, while addressing risk of bias issues. Any significant heterogeneity between studies will be explored using sensitivity and subgroup analyses.


The findings of this review will contribute to the evidence base regarding the utility of non-pharmacological insulin-sensitising treatments in enhancing conventional antidepressant treatment response.