Table 4.
Randomized controlled trials of exercise as an adjunct to standard care for major depressive disorder
| Trial | Depression diagnosis criteria and type | Sample | Interventions | Study Duration | Treatment arms (n) | Outcomes |
||
|---|---|---|---|---|---|---|---|---|
| Adherence | Drop-outs n(%) | Remission Rate % | ||||||
| Martinsen et al., 198565 | DSM Major |
Males and females, 17–60y/o, admitted to the hospital, met criteria for depression Exclusion: psychosis, physical contraindications to exercise n=49 40±NR y/o NR% males |
Inpatient setting AEx: 1hr at 50–70% of VO2max TAU: Individual psych, OT, pharm Pharm n(%) AEx: 9(NR%) CON: 14(NR%) CON: 1hr of OT |
9 weeks AEx: 3d/wk/9wks (27 supervised group sessions) CON: 3d/wk/9wks (27 supervised group sessions) |
AEx + TAU: (n=28) | NR | 4(14.1%) | NR |
| CON + TAU (n=21) | NR | 2(9.5%) | NR | |||||
| Veale et al., 199266 Study 1 |
CIS Major |
Males and females, 18–60y/o, CIS ≥17 and depression severity ≥2, concurrent treatment (pharm, psych, etc.) permitted n=83 Study 1: Age and Sex: NR Study 1 & 2: 35.5±NR y/o 36% males |
Outpatient setting AEx: Stretching warm-up, running program. Duration and intensity NR TAU: Pharm and/or psych Pharm, Psych (%): AEx: 45%, NR CON: 34%, NR CON: TAU only |
12 weeks AEx: 3d/wk/12wk (36 supervised group sessions) TAU: NR CON: No sessions beyond assessments |
AEx + TAU (n=48) | AEx: NR TAU: NA |
12(25.0%) | Remission: NR Change in BDI: 30% reduction |
| CON (n=35) | NA | 6(17.2%) | Remission: NR Change in BDI: 32% reduction |
|||||
| Veale et al., 199266 Study 2 |
CIS Major |
Males and females, 18–60y/o, CIS ≥17 and depression severity ≥2, concurrent treatment (pharm, psych, etc.) permitted n=41 Study 2: Age and Sex: NR Study 1 & 2: 35.5±NR y/o 36% males |
Outpatient setting AEx: Stretching warm-up, running program. Duration and intensity NR LO-PA: Relaxation, stretching, and yoga. Duration and intensity NR TAU: Pharm and/or psych Pharm, Psych (%): AEx: 41%, NR LO-PA: 11%, NR |
12 weeks AEx: 3d/wk/12wk (36 supervised group sessions) LO-PA: 3d/wk/12wk (36 supervised group sessions) TAU: NR |
AEx + TAU (n=63) | AEx: NR TAU: NA |
17(26.9%) | Remission: NR Change in BDI: 35% reduction |
| LO-PA + TAU (n=26) | LO-PA: NR TAU: NA |
4(15.8%) | Remission: NR Change in BDI: 40% reduction |
|||||
| Knubben et al., 200767 | DSM-IV Major |
Males and females, 20–70y/o, BRMS >12, admitted to inpatient facility, ambulatory Exclusion: associated organic disease, schizophrenic symptoms, epilepsy, ECT referral n=41 Age: NR 44.7% males |
Inpatient setting AEx: 30mins of interval (1:1) walking (5 reps of 3mins at 80% APHRM and Borg RPE 13–14 and 3mins at half speed of high interval) TAU: Pham, sleep deprivation CON: 30mins light stretching of calves, thighs, back, shoulders, and pectoral muscles (20s hold, 40s rest) |
10 days AEx:1x/d/10d (10 supervised sessions) CON: 1x/d/10d (10 supervised sessions) |
AEx + TAU (n=20) | NR | 1(5.0%) | Remission: NR Response: 65% Change in BRMS: 36% reduction |
| CON + TAU (n=18) | NR | 2(11.1%) | Remission: NR Response: 22% Change in BRMS: 18% reduction |
|||||
| Krogh et al., 200968 | ICD-10 /DSM-IV-MDI Unipolar Major |
Males and females, 18–55y/o, referred by medical doctor or psychologist and met ICD-10 criteria, Exclusion: alcohol or substance abuse, acute suicidal risk, psychotic symptoms, medical conditions that contraindicated physical exercise, been on sick leave for >24mos, exercising >1hr/wk n=165 38.9±9.5y/o 26.1% males |
Outpatient setting P-AEx: 90mins of interval training; initially 2mins on: 2mins rest at 70% MHR and progress to 3mins on:1min rest at 89% MHR. AEx included cycling, running, stepping, abdominal exercises, rowing, trampoline, step bench, jump rope, and Ski Fitter PREx: 90mins for 2–3sets x12 reps at 50% 1-RM progressed to 2-3 sets x8-10 reps at 75% 1-RM. 6 exercises on machines (leg extension, leg press, total abdominal, lower back, chest press, vertical traction) and 3 with weights (calves, arm abductors, and triceps) Relax: 90mins of light activity at Borg RPE ≤12; 20–30mins exercise on mattresses or back massage, 10–20mins of light balance activities, and 20–30mins of supine relaxation. TAU: Pharm and/or psych Pharm, Psych (%): P-AEx: 64.6%, 47.9% PREx: 66.0%, 48.9% Relax: 52.4%, 47.6% |
16 weeks All groups: 2d/wk/16wks (32 supervised group sessions) TAU: NR |
P-AEx + TAU (n=55) | P-AEx: 56.2% TAU: NA |
8(14.6%) | 40.4% |
| PREx + TAU (n=55) | PREx: 50.6% TAU: NA |
7(12.7%) | 29.2% | |||||
| Relax + TAU (n=55) | Relax: 32.8% TAU: NA |
13(23.6%) | 31.7% | |||||
| Doose et al., 201569 | ICD-10 CIS ICD-10 codes: F32.0/1/2, F33.0/1/2 Major |
Males and females, 18–65y/o, HAM-D ≥25, admitted to inpatient facility, met ICD-10 criteria, not involved in any other PA during hospitalization Exclusion: severe depressive episode (ICD-10: F32.3 or F33.3), psychotic symptoms, psychiatric comorbidities (bipolar, schizophrenia, drug addiction), pregnancy, change in psych or pharm treatment, beginning psych, relevant orthopedic disease, relevant surgery in past 6mos, acute general disease (infectious disease, anemia, cancer), poorly controlled diabetes, severe cardiovascular disease, enrolling in other clinical trial n=46 48±NR y/o 37.0% males |
Inpatient setting AEx: 10–15min warm-up; 30–45mins walking or running at self-selected intensity (mean ~12 on Borg RPE); 10–15min cool-down TAU: Pharm and/or psych Pharm, Psych (%): AEx: 50%, 53.3% CON: 75%, 68.8% CON: TAU while waitlist |
8 weeks AEx: 3d/wk/8wks (24 supervised group sessions) TAU: NR CON: Only pre- and post-intervention assessment sessions |
AEx + TAU (n=30) | AEx: 58% TAU: NA |
7(23.3%) | 63.3% |
| CON (n=16) | NA | 4(25.0%) | 0% | |||||
| Hallgren et al., 201570 | DSM-IV-MINI Major, anxiety, comorbid anxiety |
Males and females, ≥18y/o, PHQ-9 >9, Exclusion: severe somatic illness, primary drug or alcohol use disorder, psychiatric diagnosis requiring specialist treatment (i.e., psychosis) n=946 43±12 y/o 27.2% males |
Outpatient setting Ex: Randomized to 60mins of light (yoga), moderate (intermediate-level aerobics class), or vigorous (higher intensity AEx, REx and balance) exercise ICBT: Online, self-help manual with weekly interaction with clinician; additional support provided as needed TAU: Managed by PCP and included pharm and/or CBT, or no treatment Antidepressants (%) Ex + TAU: 31% ICBT + TAU: 31% CON: 24% CON: TAU “Standard tx”: 33% Pharm: 24% CBT: NR No tx: 25% |
12 weeks Ex: 3d/wk/12wks (36 supervised group sessions) ICBT: Multiple (self-selected) visits/wk/12wks (mean of 4 logins/wk and accessed 7.8±5 of 13 modules) TAU and CON: NR |
Ex + TAU (n=317) | Ex: 33% TAU: NR |
68(21.5%) | Remission: NR Change in MADRS: 49.1% reduction |
| ICBT + TAU (n=317) | ICBT: 60% TAU: NR |
58(18.3%) | Remission: NR Change in MADRS: 47.9% reduction |
|||||
| CON (n=312) | NA | 80(25.6%) | Remission: NR Change in MADRS: 34.0% reduction |
|||||
| Schuch et al., 201571 | DSM-IV-MINI Major Inpatient |
Males and females, 18–60y/o, admitted to inpatient facility, HAM-D ≥25, not involved in any other PA during hospitalization Exclusion: taking beta-blockers, psychiatric diagnosis of bipolar, schizophrenia, anorexia, substance abuse or dependence, 3 or more cardiovascular risk factors on PAR-Q, any medical condition that limits or contraindicates exercise n=50 40.3±NR y/o 28.0% males |
Inpatient setting AEx: warm-up (stretching 4 lower limb muscle groups and 4min treadmill walk), exercise bout with choice of stationary bike, treadmill, or “transport” machine at 16.5 kcal/kg body mass/wk (~59% HRR), and cool-down TAU: Pharm and/or ECT and access to OT, but no psych CON: TAU only |
Duration dependent on length of stay AEx: 3d/wk (average ~23±9d hospitalized) (Supervised individual sessions) CON: NR with average ~21±8d hospitalized |
AEx + TAU (n=25) | AEx: ~91% TAU: NA |
2(8%) | Remission: 48% Response: 84% |
| CON (n=25) | NA | 1(4%) | Remission: 32% Response: 60% |
|||||
| Helgadóttir et al., 201672 | DSM-IV-MINI Major, anxiety, comorbid anxiety |
Males and females, 18–67 y/o, PHQ-9 ≥10, Exclusion: primary diagnosis or alcohol or drug dependency, serious somatic disorder, psychiatric diagnosis requiring specialist treatment (i.e., psychosis) n=620 42.6±12.0 y/o 26.3% males |
Outpatient setting AEx-Vig: 60mins of strenuous group aerobics class AEx-Mod: 60mins of intermediate-level group aerobics class AEx-Light: 60mins of yoga-based stretching and balance TAU: Managed by PCP and included pharm and/or CBT, or no treatment CON: TAU |
12 weeks AEx groups: 3d/wk/12wks (36 supervised group sessions and weekly individual session with study personnel) TAU and CON: NR |
AEx-Vig + TAU (n=99) |
AEx: NR TAU: NA |
19(19.2%) | Remission: NR Change in MADRS: 38.4% reduction |
| AEx-Mod + TAU (n=105) |
AEx: NR TAU: NA |
27(25.7%) | Remission: NR Change in MADRS: 32.9% reduction |
|||||
| AEX-Light + TAU (n=106) |
AEx: NR TAU: NA |
21(19.8%) | Remission: NR Change in MADRS: 44.1% reduction |
|||||
| CON (n=310) | NA | 79(25.5%) | Remission: NR Change in MADRS: 25.4% reduction |
|||||
| Olson et al., 201773 | DSM-IV-MINI Major |
Males and females, 18–30y/o, met non-psychotic depression criteria, no pharm or psych beyond >6wk stable dose of antidepressants or mood stabilizers, no regular exercise or pst mo (<35kcal/kg/day or <3d/wk for ≤20min/session), no physical limitations or contraindications to exercise, normal or corrected-to-normal vision Exclusion: severe psychopathology (substance dependence, bipolar, schizophrenia disorders), suicidal risk, planned or current pregnancy n=50 Age: NR 24.0% males |
Outpatient setting AEx: 45mins of steady-state exercise (treadmill or cycle ergometer) at 40–65% HRR TAU: Stable dose of antidepressants or mood stabilizers permitted, but no psych ~ 14% of sample reported using pharm CON: 30–45mins of light stretching in sitting and standing |
8 weeks AEx: 3d/wk/8wks (24 supervised sessions) TAU: NR CON: 3d/wk/8wks (24 supervised sessions) |
AEx + TAU (n=25) | AEx: 100% TAU: NR (only completers reported) |
10(40%) | 60% |
| CON + TAU (n=25) | NR | 10(40%) | 33% | |||||
| Buschert et al., 201974 | ICD-10 Unipolar depression Comorbid: ICD-10 chapters of F4, 5, 6 permitted |
Males and females, admitted to inpatient facility with unipolar depression Exclusion: psychotic symptoms, comorbid psychiatric disorders (except ICD-10 chapters F4, 5, and 6), cardiovascular or neurological disease, cognitive impairment n=38 41.2±9.1 y/o 36.7% males completed study |
Inpatient setting AEx: 30mins of endurance training (outdoor walking, Nordic walking, running, or stationary cycling) at 85% of APMHR TAU: Only pharm reported CON: Additional 30mins OT or AT session |
3 to 4 weeks AEx: 2–3d/wk/3–4wks (6 –12 supervised group sessions) TAU: NR CON: 2–3d/wk/3–4wks (6 –12 supervised group sessions) |
AEx + TAU (n=20) |
Mean sessions: 10.00±3.0 | 5(25.0%) | Remission: NR Change in BDI-II: 37.2% reduction HAM-D7: 34.5% reduction |
| CON + TAU (n=18) |
Mean sessions: 14.3±8.2 | 3(16.7%) | Remission: NR Change in BDI-II: 31.5% reduction HAM-D7: 33.0% reduction |
|||||
| Chau et al., 202075 | ICD-10 Major (F33.0 – F3.9 ICD-10 codes) |
Males and females, 18–64y/o, met ICD-10 diagnosis codes (F33.0–F33.9) Exclusion: unstable medical or psychological states (suicidal risk), severe cognitive, language or hearing deficits; and orthopedic conditions or other diseases that limit physical fitness assessment n= 84 47.4±10.6 y/o 20.2% males |
Outpatient setting Ex: 45mins for stretching warmup, circuit training (3 stations of AEx at 50–70% MHR and 3 stations of REx [3×10 reps of each major muscle group]), and 15mins stress management, mindful breathing, stretching, and body awareness (60min total) TAU: Only pharm noted Ex: 83% CON: 83% CON: TAU waitlist instructed not to initiate structured exercise program |
12 weeks Ex: 3ds/wk/12wks (36 supervised group sessions) CON: NA |
Ex + TAU (n=42) | NR | 6(15%) | Remission: NR Change in HAM-D17: 51.5% reduction |
| CON + TAU (n=42) | NR | 7(17.5%) | Remission: NR Change in HAM-D17: 15.6% reduction |
|||||
| Haussleiter et al., 202076 | DSM-IV-SCID Major |
Males and females, admitted for inpatient care, HAM-D ≥17, Exclusion: Acute suicidality, severe comorbid psychiatric disorders, medical contraindications to PA, cognitive impairment, unable to complete self-administered questionnaires n=111 per protocol analysis: n=76 45.05±12.19 y/o 33.3% male (full sample) ~68% male (per protocol) |
Inpatient setting GET: 50mins of group exercise of mixed modalities SOA: Encouraged to perform PA. Meetings to discuss physical conditions, depressive symptoms, and motivational troubles. TAU: antidepressant and psychoactive medications as prescribed (type and dosage NR) Mean number of antidepressants GET: 1.26±0.60 SOA: 1.02±0.73 Mean number of psychoactives GET: 1.72±1.00 SOA: 2.03±1.14 |
6 weeks GET: 3d/wk/6wks (18 supervised group sessions) SOA: 3d/wk/6wks (18 supervised group meetings) TAU: NR |
GET + TAU (n=36) |
NR | Full sample: Within 3wks: 35 (31.5%) Baseline to 6wks: NR |
HAM-D at 3wks: Response: 38.9% Remission: 27.8% HAM-D at 6wks: Response: 54.5% Remission: 40.9% |
| SOA + TAU (n=40) |
NR | HAM-D at 3wks: Response: 25.0% Remission: 10.0% HAM-D at 6wks: Response: 55.6% Remission: 25.9% |
||||||
| La Rocque et al., 202177 | DSM-V-SCID Unipolar depressive disorder |
Females, non-chronic unipolar depressive disorder Exclusion: psychotic, bipolar, or substance disorder, suicidal intent, medical condition interfering with PA, pregnancy, recent change (<3mos) in pharm or psych, participating in group or yoga exercise bi-weekly or more not obtaining physician clearance with moderate or high risk on PAR-Q n=53 Per protocol analysis: n=42 ~33 y/o 0% males |
Outpatient setting BY: 90mins of instructor-led group Bikram yoga class AEx: 50–60min group exercise class of choice (choreography-based cardio, aerobics, light muscular conditioning, and stretching; cardio, plyometric, and strength training; high intensity aerobic exercise with intermittent rest periods; circuit-based cardio and strength training; stepper-based exercises; and Latin-inspired dance/ fitness) CON: Waitlist with no interventions TAU: Continue pharm and/or psych with participant’s own healthcare provider BY: 8(44.4%) Pharm: 4(22.2%) Psych: 3(16.7%) Both: 1(5.6%) AEx: 9(45.0%) Pharm: 4(20.0%) Psych: 4(20.0%) Both: 1(5.0%) CON: 7(46.6%) Pharm: 7(46.6%) Psych: 0(0.0%) Both: 0(0.0%) |
8 weeks BY: 2d/wk/8wks (instructor led group classes) AEx: 2d/wk/8wks (instructor led group class of choice) CON: no access to classes TAU: as prescribed by healthcare provider |
BY + TAU (n=18) | ITT: 68.8% Per protocol analysis: 80% |
3(16.7%) | Remission (ITT): 61% Response (per protocol): 73.3% |
| AEx + TAU (n=20) | ITT: 66.9% Per protocol analysis: 86% |
5(25.0%) | Remission (ITT): 60% Response ITT: 60.0% Per protocol; 80.0% |
|||||
| CON + TAU (n=15) | N/A | 3(20.0%) | Remission: NR Response ITT: 6.7% Per protocol: 8.3% |
|||||
AEx = aerobic exercise; AEx-Light = exercise-light intensity; AEx-Mod = exercise-moderate intensity; AEx-Vig = exercise-vigorous intensity; APHRM = Age predicted maximum heart rate; AT = art therapy; BDI = Beck Depression Inventory; BMI = body mass index; BRMS = Bech-Rafaelsen Melancholy Scale; BY = bikram yoga; CBT = cognitive behavioral therapy; CIS = Clinical Interview Schedule; CON= control; d = day(s); DSM = Diagnostic and Statistical Manual of Mental Disorders, edition not reported; DSM-IV = Diagnostic and Statistical Manual of Mental Disorders, fourth edition; ECT = electroconvulsive therapy; Ex = exercise; GET = guided exercise therapy; HAM-D = Hamilton Depression Rating Scale; hr(s) = hours(s); HRR = heart rate reserve; ICBT = internet-based cognitive-behavioral therapy; ICD-10 = International Classification of Diseases, 10th Revision; ITT = intention to treat; LO-PA = low intensity physical activity; MADRS = Montgomery Depression Rating Scale; MDI = Major Depression Inventory; MHR = maximum heart rate; min(s) = minute(s); MINI = Mini International Neuropsychiatric Interview; NA= not applicable; NR = not reported; OT = occupational therapy; PA = physical activity; P-AEx = progressive aerobic exercise; PAR-Q = Physical Activity Readiness Questionnaire; PCP = primary care physician; Pharm = pharmacotherapy; PHQ-9: Patient Health Questionare-9; PREx = progressive resistance exercise; Psych = psychotherapy; Relax = relaxation; REx = resistance exercise; RPE = rate of perceived exertion; s = seconds; SCID = Structured Clinical Interview of DSM Disorders; SNRIs = serotonin and norepinephrine reuptake inhibitors; SOA = self-organized activity; SSRIs = selective serotonin reuptake inhibitors; TAU = treatment as usual; VO2max = maximal oxygen uptake; wk(s) = week(s); y/o = years old; 1-RM = one-repetition maximum