Physical activity in the treatment-resistant depression and non-remitted depression: a systematic review of randomized controlled trials

<ns5:p>Background The objective of this systematic review was to analyze the effects of physical activity (PA) intervention as an adjuvant strategy to pharmacological treatment in people with treatment-resistant depression (TRD) and non-remitted depression (NRD). Methods A search strategy was conducted from five databases: PubMed, Cochrane Central Register of Controlled Trials, Scopus, SPORTDiscus, and Web of Science. The Physiotherapy Evidence Database and Oxford’s Evidence Levels were used to classify the quality appraisal. Results Of the 10777 records, 11 randomized controlled studies met the inclusion criteria, comprising 567 participants (n=275 from the TREAD project across eight sub-studies; n=292 from three independent Randomized control trials). The main outcome for this analysis was the effect of physical activity (PA) or exercise on depressive symptoms in people with TRD and NRD diagnosis. According to the FITT (Frequency, Intensity, Time, and Type) principle, there was some variability in the PA intervention. However, except for one article, all were classified as excellent in terms of quality description. Conclusions Based on moderate-quality evidence from three independent RCTs, structured exercise programs may be considered as an adjunctive intervention for depressive symptoms in patients with TRD and NRD. Evidence for other outcomes (quality of life, sleep, cognition, biomarkers) is of low or very low quality, derived from single studies or non-independent TREAD sub-analyses. Future research should prioritize independent replication of secondary outcomes and pre-specified analyses of predictors of response. Further high-quality RCTs in this population are urgently needed to confirm these findings and establish optimal PA protocols.</ns5:p>