Abstract
BackgroundDepression 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.Methods/designIn 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.DiscussionThe 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.
Highlights
Depression is the leading cause of disability worldwide and is known to be associated with insulin resistance (IR)
This systematic review will qualitatively and quantitatively analyse trials assessing antidepressant treatment response following adjunctive insulin sensitising lifestyle and dietary-related interventions. These interventions include exercise, magnesium supplementation, vitamin D supplementation, zinc supplementation, probiotics, n-3 polyunsaturated fatty acids, monounsaturated fatty acids as well as hygienic-dietary recommendations which involves strict prescriptions of regulated daily exercise, healthy diet, hygienic sunlight exposure and hygienic sleep habits
This is further corroborated by studies which showed that exercise increases levels of brain-derived neurotrophic factor (BDNF) [82,83,84], a trophic factor known to promote functional and structural brain plasticity, associated with antidepressant effect
Summary
The evidence-based association between depression and insulin resistance as well as the observed increased severity of depressive symptoms and the reported antidepressant ineffectiveness in patients with comorbid depression and insulin resistance warrant further investigation. This systematic review will qualitatively and quantitatively analyse trials assessing antidepressant treatment response following adjunctive insulin sensitising lifestyle and dietary-related interventions These interventions include exercise, magnesium supplementation, vitamin D supplementation, zinc supplementation, probiotics, n-3 polyunsaturated fatty acids, monounsaturated fatty acids as well as hygienic-dietary recommendations which involves strict prescriptions of regulated daily exercise, healthy diet, hygienic sunlight exposure and hygienic sleep habits (combined in any form or any of these used as a stand-alone adjunct). It is expected that this systematic review with meta-analysis will open a new ‘window’ regarding the potential basis for or mechanism involved in the antidepressant treatment response improvement observed with the use of the above-stated interventions as adjunctive therapy for depression.
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