Table 1.
Clinical trials of physical activity in persons with mood disorders. To determine the effects of PA on the brain in humans affected by MDs, a computer search of MEDLINE using the terms “mood disorder,” “physical activity,” and “exercise” was used to produce a list of interventional studies. Then, manual searches of key references were performed to identify additional studies. Articles met inclusion criteria if they were peer-reviewed interventional studies in persons diagnosed with MDD or BP. Articles were excluded if they were reviews, case reports, conference abstracts, expert opinions, or clinical studies of adolescents. Duplicate articles and those not available in English language were excluded also. Based on this search and subsequent screening, 37 articles that spanned from 1987 to 2016 were identified. Whereas extensive variations existed in the studies with regard to age, sex, degree of symptoms, phase of disease, and setting, 97% of RCTs (31 out of 32) that measured behavioral outcomes reported positive associations between PA and recovery from depressive symptoms [40, 41, 267, 316, 463–489] by utilizing training ranges of 100–250 min per week for a duration of 2–6 months [40, 41, 316, 463–468, 472–474, 476–485, 487, 488]. One report achieved relief of depressive symptoms following 60 minutes of PA for a duration of 5 weeks [489], whereas another study reported that participants obtained relief following PA 30 min/day for a duration of 1 week [470]. The modalities used in the programs varied, but most of the programs deployed some form of aerobic activity as a core component [40, 41, 96, 464–483, 485–488, 490, 491]. Notably, the one study that failed to find an association between PA and depressive symptoms used a relaxation group as a control [492], a fact that may be problematic given preliminary evidence that stress reduction activities reduce cortisol abnormalities and, in turn, may mitigate depressive symptoms [489]. The remaining studies reported that PA reduced sleep problems [382, 383, 487]; normalized BDNF levels in some studies [267, 268], but failed to do so in others [490]; and reduced cortisol levels [489]. Nevertheless, extant RCTs are still few and leave many questions unresolved.
| References | Sample | Modality | Frequency & duration of PA | Assessment |
|---|---|---|---|---|
| [463] | Mean age of 75 y/o with MDD (n = 121) | Sertraline only; sertraline + supervised nonprogressive PA (<70% peak heart rate); sertraline + supervised progressive aerobic activity (60% peak heart rate) |
60 min/session 3 d/wk for 24 wks | Reduced depressive symptoms on HAM-D and CGI in all groups, but earlier and higher remission rates in exercise groups at 4, 8, and 12 wks |
| [464] | 50 y/o or greater with MDD (n = 156) | Aerobic exercise (70–85% max HR); aerobic exercise (70–85% max HR) + standard medication; or standard medication only | Supervised 45 min sessions 3 d/wk × 16 wks | Reduced depressive symptoms on BDI and HAM-D in all groups, but response was quicker in medication-only group |
| [465] | 19–78 y/o with depressive symptoms (n = 112) |
Aerobic exercise outside during daylight hours (60% max HR) + prompts to take a specific vitamin regimen or control | 20 min per session 5 d/wk × 8 wks | Reduced depressive symptoms in both groups, but more so in exercise group; specifically, ↓ depressive symptoms on CES-D in exercise group; ↓ anger and tension on POMS in exercise group; ↑ vitality in exercise group |
| [466] | 18–65 y/o with MDD (n = 62) | Add-on aerobic exercise × 10 wks; add-on basic body awareness therapy × 10 wks; or single consult for advice on PA + care as usual | 55–60 min session 2 d/wk × 10 wks; group basic body awareness therapy 2 d/wk × 60 min; or advice on PA on one occasion | Reduced depressive symptoms on MADRS in all groups (−10.3 in aerobic PA, −5.8 in body awareness, and −4.6 in advice only group); ↑ cardiovascular fitness gains in aerobic exercise group; ↓ self-rated depression symptoms in PA and basic body awareness groups |
| [41] | 50 y/o or greater with MDD (n = 133) | Aerobic activity (70–85% max HR); aerobic activity (70–85% max HR) + sertraline; or sertraline only | Supervised 45 min sessions 3 d/wk × 16 wks then follow-up 24 wks after study conclusion | Reduced depressive symptoms on HAM-D; ↑ rate of partial or full recovery from depressive symptoms on HAM-D in exercise group; and ↓ rate of relapse for MDD in exercise group |
| [316] | 18–20 y/o with mild to moderate depression (n = 28) | Exercise regimen or usual daily activities | 50 min sessions 5 d/wk × 8 weeks for each regimen | Exercise regimen reduced depressive symptoms on CES-D; ↓ cortisol; and ↓ urinary secretion of epinephrine |
| [467] | 20–64 y/o with MDD (n = 82) | Aerobic exercise + care as usual or care as usual only | Progressive exercise 45–60 min per session 3 d/wk × 8 wks | Combination of exercise + fluoxetine group exhibited greater reduction in depressive symptoms on BDI and ICD-10 than fluoxetine alone |
| [468] | 18–35 y/o with MDD or minor depression (n = 40) | Aerobic (80% max HR); strength training (50–60% max HR); or control |
Supervised sessions 4 d/wk × 8 wks | Reduced depressive symptoms on BDI and HAM-D in both exercise groups following intervention and at 12 mo follow-up |
| [469] | 20–45 y/o with diagnosis of MDD (n = 80) | 4 aerobic exercise treatment groups that varied according to intensity: low dose (7.5 kcal/kg/wk for 3 or 5 d/wk × 12 wks); high dose (17.5 kcal/kg/wk for 3 or 5 d/wk × 12 wks); or control | Supervised aerobic activity × 12 wks | Reduced depressive symptoms on HAM-D for high-dose aerobic exercise (17.5 kcal/kg/wk 3–5 d/wk) |
| [470] | 20–53 y/o with MDD (n = 38), somatization syndrome (n = 26), or healthy controls (n = 47) |
Aerobic exercise or control | 30 min/d for 1 wk or reduced PA for 1 wk | Reduced depressive symptoms on BDI 2 following 1 wk of exercise in persons with MDD, but not other groups; ↑ monocytes in healthy controls, but not in persons with MDD or somatization syndrome |
| [471] | 18–65 y/o with MDD and sedentary lifestyle and with residual cognitive or attention impairments following tx with SSRIs for 8–12 wks (n = 39) | High-dose aerobic exercise (target of either 16 KKW—the equivalent to walking 4 mph × 210 min/wk) or low-dose aerobic control (4 KKW—the equivalent to walking 3.0 mph for 75 min/wk) | Initial supervision during sessions then transition to home-based program × 12 wks | Reduced depressive symptoms in both groups on IDS-C, but greater effect in high-dose exercise group; high dose PA ↑ spatial working memory and both groups ↑ cognitive function (psychomotor speed and executive function) |
| [472] | 60 y/o or greater women who were overweight or moderately depressed (n = 106) | Add-on supervised aerobic exercise + strengthening activities or usual care | Supervised 50 min session 3 d/wk × 24 wks | Reduced depressive symptoms and anxiety on GDS, STAI, and EQ-5D in intervention group; ↓ BMI in intervention group |
| [473] | 40 y/o or greater with diagnosis of MDD (n = 102) | Supervised aerobic exercises (70–85% of max HR); sertraline; or placebo | 45 min session 3 d/wk × 16 wks | Reduced depressive symptoms in both groups on HAM-D and BDI along with higher remission rates compared to placebo; ↔ between groups in verbal memory, verbal fluency, or working memory |
| [40] | Mean age of 51 y/o with MDD and sedentary (n = 202) | Supervised aerobic exercise (70–80% of max HR); home-based exercise; sertraline; or placebo | 45 min session 3 d/wk × 16 wks | At 12 mo follow-up, exercisers who reported 180 min/wk exhibited reduced depressive symptoms on HAM-D scores and a ↓ risk for relapse in comparison with persons who reported 0 min of exercise |
| [474] | 18 y/o or greater with MDD (n = 42) | Structured group exercise (50% max HR) or usual care |
45 min session 3 d/wk × 6 wks | Reduced depressive symptoms on MADRS and BDI-2 in both groups, but ↑ response (> 50% decrease of symptoms on MADRS) in exercise group; ↓ diastolic blood pressure in exercise group; ↓ waist circumference in exercise group; ↑ HDL in exercise group; ↑ cardiorespiratory capacity in exercise group |
| [475] | 75 y/o or greater with depressive symptoms (n = 193) | Individualized; home-based exercise program (i.e., balance, strength, and aerobic activity); or control | 52 wks | Reduced depressive symptoms on GDS and ↑ mental health-related quality of life in both groups, but no difference between groups |
| [476] | 18 y/o or greater with depressive symptoms (n = 23) | Low-frequency aerobic exercise (within target HR); high-frequency aerobic exercise; or high-frequency aerobic exercise + group team building intervention | 1 aerobic activity 30 min session 1 d/wk × 8 wks; 30 min session 3–5 d/wk × 8 wks; 30 min session 3–5 d/wk + group team building × 8 wks | Persons in high-frequency aerobic groups exhibited reduced depressive symptoms on BDI-2, but team-building intervention ↔ depressive symptoms |
| [477] | 22–63 y/o with depressive symptoms (n = 80) |
Aerobics + bright light or aerobics + normal light | Individualized aerobic training 2-3 d/wk × 8 wks | At 8 wks, reduced depressive symptoms on HAM-D and ATYP in both groups, but greater effect in aerobics + bright light group; ↑ in vitality on RAND in both groups, but more so in bright light group |
| [478] | 26–63 y/o with depressive symptoms (n = 98) |
Aerobics + bright light; aerobics + normal light; or stretching in bright light | Supervised sessions 2 d/wk × 8 wks | Reduced depressive symptoms on HAM-D in both aerobic groups; reduced depressive symptoms on SIGH-SAD-SR in aerobic + bright light group; ↔ in serum lipid levels or BMI in any group |
| [485] | 31–52 y/o with dysthymia and MDD (n = 99) | Add-on aerobic exercise (70% max HR); nonaerobic exercise; or usual care | Supervised 60 min sessions 3 d/wk × 8 wks | Reduced depressive symptoms on BDI in both exercise groups; ↑ VO2 max in aerobic exercise group |
| [479] | 21–70 y/o or greater with MDD or BD (n = 75) | Chronotherapeutic intervention (consisting of wake therapy, bright light therapy, sleep phase advance, and sleep time stabilization) or individualized aerobic exercise plan | 30 min sessions 5 d/wk × 29 wks | Reduced depressive symptoms on HAM-D in both groups, but even greater response in chronotherapy group—at 9 wks remission rate was 45% for chronotherapy group versus 23% for PA group and at 29 wks remission was 62% for chronotherapy group versus 38% for PA group |
| [480] | 53 y/o or greater with mood disorder who were poor responders to antidepressant meds (n = 86) |
Add-on exercise (aerobic, strengthening, and stretching) or health education talks | Supervised activity for 60 min session 2 d/wk × 10 wks | Reduced depressive symptoms on HAM-D in both groups, but response more positive in exercise group |
| [487] | 65 y/o or greater with and without depressive symptoms who are sedentary (n = 451) | Aerobic exercise (60 to 80% max HR) or progressive strength training (50–75% 1 rep max) | Supervised training 60 min session 3 d/wk × 10/wks | Reduced depressive symptoms on GDS in both strength training and aerobic exercise groups; ↑ plasma BDNF in strength training group |
| [481] | 60 y/o or greater with osteoarthritis of knee and depressive symptoms (n = 438) |
Aerobic exercise (50–70% max HR); strength training; or health education | Supervised walking 60 min session 3 d/wk then home-based aerobic activity × 15 mo or supervised progressive strength training 60 min session 3 d/wk × 3 mo + home-based continuation of training × 15 mo | Reduced depressive symptoms on CES-D in aerobic exercise group; ↔ depressive symptoms on CES-D in strength training group; both aerobic and strength training ↓ pain, ↓ self-reported disability, and ↑ walking speed |
| [486] | 50 y/o or greater with MDD (n = 200) | Add-on aerobic home-based program (target of 150 min per wk) and strength training + usual care or usual care only | Exercise 3 d/wk for strength training for all major muscle groups + 30 min session aerobic activity 5 d/wk × 12 wks | Reduced depressive symptoms on MADRS in both groups at 12-, 26-, and 52-week follow-up assessments |
| [489] | 18–65 y/o with MDD (n = 60) | Add-on yoga to quetiapine fumarate or escitalopram or no yoga | Supervised 60 session 1 d/wk × 5 wks | Reduced depressive symptoms on HAM-D; trend towards ↓ cortisol secretion in both groups |
| [482] | 18–60 y/o with MDD (n = 26) | Add-on aerobic exercise at patient selected intensity + usual care or usual care only | 16.5 kcal/kg/wk × 3 d/wk | Reduced depressive symptoms on HAM-D and QoL measure in psychological domain |
| [483] | 18–60 y/o severely depressed inpatients with MDD (n = 50) |
Add-on aerobic PA (with goal of 15.5 kcal/kg/wk) + usual care or usual care only |
Supervised session 3 d/wk (mean length 23.36 days ± 9 days) | Reduced depressive symptoms on HAM-D and ↑ quality of life (World Health Organization Quality of Life Assessment Instrument-Brief version (WHOQOL-BREF) during second wk of treatment and at discharge |
| [484] | 69–73 y/o with MDD, minor depressive symptoms, or dysthymia (n = 32) |
Progressive resistance training (3 sets of 8 repetitions of 80% 1 rep max) × 10 wks + unsupervised exercise or health education |
Supervised 45 min sessions 3 d/wk × 10 wks followed by unsupervised resistance training 2-3 d/wk × 10 wks | Reduced depressive symptoms in exercise group on BDI at 20 wks and 26 mo follow-up; ↑ morale on measures of aging on the Philadelphia Geriatric Morale Scale |
| [488] | 18–55 y/o with MDD (n = 57) | Add-on aerobic exercise (60–85% VO2 max) + sertraline or sertraline only |
Supervised sessions 4 d/wk × 4 wks | Reduced depressive symptoms on HAM-D in both groups, but response occurred with lower dosage in exercisers; ↑ VO2 max in exercisers |
| [492] | 18–55 y/o with MDD who were medicated and unmedicated and received psychotherapy (n = 165) | Strength training (2 or 3 trials of 12 reps at 50% max and increasing to 8 reps of 75% max); aerobic exercise (70% max heart rate); or control (stretching and relaxation groups (n = 55 for each) | Supervised training 90 min per session 2 d/wk × 16 wks | ↔ in depressive symptoms between three groups on HAM-D at 4 mo and 12 mo; ↔ in cognitive symptoms between the three groups at 4 mo and 12 mo |
| [268] | 50 y/o or greater with remitted MDD (n = 35) | Modified incremental walking protocol | Supervised single 30 min exercise bout | ↑ BDNF towards levels comparable to healthy controls |
| [267] | 22 y/o or greater with MDD (n = 18) | Progressive exercise until 125 beats per minute | Supervised single aerobic exercise bout | ↑ BDNF |
| [383] | 18–70 y/o with nonremitted MDD (n = 126) | Augmentation of SSRI with 16 kilocalories per kilogram of body weight per wk × 12 wks (equivalent to 150 min per wk at moderate intensity) or 4 kilocalories per kilogram of body weight per wk × 12 wks |
Sensor monitored and partially supervised × 12 wks | ↓ in hypersomnia on IDS-C, a change that was correlated with ↓ BDNF and ↓ IL-1β; lower baseline levels of IL-1β predicted greater improvements in insomnia |
| [490] | 18–60 y/o with MDD (n = 79) | Aerobic exercise (80% aerobic capacity) or control | Supervised 45 min sessions 3 d/wk × 3 mo | ↔ hippocampal volume; BDNF; VEGF; or IGF-1 in exercise group |
| [382] | 18–70 y/o with nonremitted MDD (n = 122) | Augmentation of SSRI with 16 kilocalories per kilogram of body weight per wk × 12 wks (equivalent to 150 min per wk at moderate intensity) or 4 kilocalories per kilogram of body weight per wk × 12 wks | Sensor monitored and partially supervised × 12 wks | ↓ insomnia as measured on IDS-C in both groups |
| [491] | 18–60 y/o with MDD (n = 53) versus healthy controls (n = 58) | Aerobic exercise (80% max heart rate) or control | Supervised sessions 45 min session 3 d/wk × 3 mo | ↓ at-rest levels of copeptin in participants with high exercise compliance |
ATYP: Atypical Depression Symptoms Addendum to Hamilton Depression Rating Scale; BAI: Beck Anxiety Inventory; BDI: Beck Depression Inventory; CES-D: Center for Epidemiologic Studies Depression; GWB: General Well-Being Schedule; GDS: Geriatric Depression Scale; HAM-D: Hamilton Depression Rating Scale; ICD-10-D: International Classification of Diseases-Depression; IDS-SR: Inventory of Depressive Symptomatology-Self Reported; POMS: Profile of Mood States; GCPS: Graded Chronic Pain Scale; CGI: Global Improvement of Depression; MADRS: Montgomery and Asberg Depression Rating Scale; QoL: quality of life; QALY: quality-adjusted life years using EuroQol (EQ-5D); RAND: RAND 36-Item Health Survey; SIGH-SAD-SR: Seasonal Affective Disorders Version Self-Rating Format; STAI: State-Trait Anxiety Inventory; WHOQOL-BREF: World Health Organization Quality of Life Assessment Instrument-Brief version.