EXERCISE AS AN AUGMENTATION TO PHARMACOTHERAPY FOR DEPRESSION IN OLDER AND YOUNGER ADULTS: A FEASIBILITY TRIAL EXPLORING BIOLOGICAL MECHANISMS

Abstract

Introduction Exercise interventions for depression that also examine biological mechanisms are rare and none have included both younger and older adults with Major Depression. Our pilot intervention study tested the feasibility of conducting a physical exercise intervention as augmentation to pharmacotherapy for depression in younger and older adults while also exploring possible neural mechanisms underlying the antidepressant effects of exercise. Methods Fifteen sedentary younger (20-39 years) and older adults (60-79 years) meeting criteria for a Major Depressive Episode were randomized to receive a 12-week medication regimen of venlafaxine XR or venlafaxine XR plus physical exercise. The exercise intervention involved supervised moderate-intensity aerobic exercise sessions three times per week for 12 weeks. The primary aim was to develop the infrastructure for conducting an exercise intervention in adults with Major Depression while also collecting brain imaging measures to better understand mechanisms. The Montgomery Asberg Depression Rating Scale (MADRS) was used to assess change in depressive symptoms, the VO2submaximal test was used to assess change in cardiorespiratory fitness, and 7T structural MR imaging was used to assess change in regional brain morphology (i.e., cortical thickness) relevant to depression. Data analysis was conducted using repeated measures ANOVA and paired-samples and independent samples t-tests. Results Our results demonstrated feasibility of conducting a physical exercise intervention combined with pharmacotherapy trial in depressed younger and older adults. Ten younger adults and five older adults were randomized to receive treatment and 11 participants completed the study. There was 0% attrition and a 91% attendance rate (i.e., 33/36 sessions) among participants engaged in the exercise intervention. Although efficacy of the intervention was unable to be tested, trends suggested that the addition of physical exercise to medication treatment for depression may lead to rapid and stable decline in depressive symptoms and exercise-related improvements in cardiorespiratory fitness may be linked to an increase in cortical thickness in regions sensitive to depression (i.e., orbitofrontal cortex, anterior cingulate cortex, parahippocampal gyrus). Further, sensitivity analyses suggested that treatment-related increases in cortical thickness in the right medial orbitofrontal cortex and right rostral anterior cingulate cortex were associated with improved performance on measures of verbal learning and memory (p Conclusions This pilot clinical trial involving physical exercise as an augmentation to antidepressant medication treatment enabled this interdisciplinary research team to develop the infrastructure for conducting an exercise intervention for depression in late-life and early adulthood while also examining biological mechanisms. Recruitment challenges were overcome, and intervention adherence was exceptional. Trending associations between exercise-related improvements in fitness and changes in cortical thickness are promising avenues for future large-scale studies to explore. This research was funded by This project was supported by the Advanced Center for Intervention and Services Research (ACISR). PDF: http://submissions.mirasmart.com/Verify/AAGP2019/Original/AAGP2019-000336/AAGP2019-000336_Fig1.pdf PDF: http://submissions.mirasmart.com/Verify/AAGP2019/Original/AAGP2019-000336/AAGP2019-000336_Fig2.pdf