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Exercise in the Treatment of Depression. Sean T. Mullendore Major, USAF, MC Primary Care Sports Medicine Fellow. Objectives. Scope of problem Depression defined Evidence of exercise to treat depression Proposed mechanisms of effect Limitations of evidence/application Bottom line.

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exercise in the treatment of depression

Exercise in the Treatment of Depression

Sean T. Mullendore

Major, USAF, MC

Primary Care Sports Medicine Fellow

  • Scope of problem
  • Depression defined
  • Evidence of exercise to treat depression
  • Proposed mechanisms of effect
  • Limitations of evidence/application
  • Bottom line
scope of problem depression
Scope of Problem – Depression
  • Prevalence between 5-10% of adults in primary care in U.S.
  • 2-3X have depressive symptoms without DSM-IV criteria
  • Women affected 2X as often as men
  • Depressive disorders are 4th most important cause of disability worldwide
  • Mild-moderate major depressive disorder ranks 2nd to ischemic heart dz for years of life lost due to premature death/disability
depression presentations risk factors

Multiple medical visits

Multiple somatic complaints

Work/relationship dysfunction

Sleep disturbance

Volunteered c/o stress or mood disturbance

Risk Factors

Family/personal hx

Chronic medical illness

Major life change

Stressful life event(s) involving loss

Depression – Presentations/Risk Factors
depression screening tools
Depression – Screening Tools
  • Validated instruments as adjuncts to clinical interview
    • Beck Depression Inventory (BDI)
    • Hamilton Rating Scale for Depression (HAM-D)
    • Quality Improvement for Depression Scale (QIDS)
depression defined
Depression Defined
  • Diagnostic and Statistical Manual of Mental Disorders, 4th Edition Text Revision (DSM-IV TR)
    • 5 or more symptoms present during same 2-week period
    • At least 1 symptom either
      • Depressed mood OR
      • Loss of interest/pleasure
other disorders to consider
Other Disorders to Consider…
  • Dysthymia
  • Adjustment disorder with depressed mood
  • Bipolar disorder
  • Substance abuse
  • Overtraining/“staleness”
descriptive cross sectional data
Descriptive & Cross-Sectional Data

Camacho et al, Am J Epidemiol 1991

  • Participant activity levels & depressive sxs measured in 1965, 1974, & 1983
  • Significant risk for depression at 1974 follow-up if inactive at baseline
  • Changes in exercise habits between 1965-1974 may have changed risk of depression in 1983 (i.e. more active = less depression and vice versa)
descriptive cross sectional data1
Descriptive & Cross-Sectional Data

Bäckmand et al, Int J Sports Med, 2001

  • Male athletes representing Finland from 1920-1965 with controls classified as healthy at age 20
  • 5 athlete groups: endurance, power/combat, power/individual, team, shooting
  • Questionnaires completed in 1985 & 1995
  • Finding: Referents more depressed than endurance and team sport athletes
descriptive cross sectional data2
Descriptive & Cross-Sectional Data

Bäckmand et al, Int J Sports Med, 2003

  • Former elite male athletes surveyed by questionnaire in 1985 & 1995
  • Findings:
    • Low levels of physical activity significantly increased risk of depression
    • Increase of 1 MET-unit (hour/day) statistically decreased risk of depression by 8%
randomized controlled trial
Randomized Controlled Trial

Blumenthal JA et al, Arch Intern Med , 1999

  • InfoPOEMs level of evidence 1b
  • 156 depressed older patients randomly assigned to 1 of 3 groups
    • Supervised aerobic exercise at 70%-85% of heart rate reserve for 30 minutes on 3 days per week
    • Zoloft Rx at 50 mg to 200 mg daily
    • Both aerobic exercise and Zoloft Rx
  • Primary outcomes = scores on Hamilton Rating Scale for Depression (HAM-D) and Beck Depression Inventory (BDI)
blumenthal ja et al cont d
Blumenthal JA et al (Cont’d)
  • Findings at 4 months…
    • All 3 groups achieved comparable & significant remission of MDD based on DSM-IV criteria
      • 60.4% in exercise group
      • 68.8% in Zoloft group
      • 65.5% in exercise + Zoloft group
    • Patients on Zoloft Rx alone responded faster
    • Among patients receiving combination tx, those with less severe MDD responded more quickly to exercise + Zoloft than those with more severe MDD
  • Bottom line:
  • Exercise – walking or jogging – at 70%-85% of maximum aerobic intensity is as effective as Zoloft therapy in treating mild MDD
  • Zoloft therapy had a faster initial response than exercise in improvement of MDD symptoms
systematic review
Systematic Review

Lawlor et al, BMJ, 2001

  • Outcomes = mean differences in effect size in BDI score between exercise & no treatment and between exercise & cognitive therapy
  • 72 potentially relevant studies; 56 were excluded from analysis
lawlor et al cont d
Lawlor et al (Cont’d)
  • Findings…
    • Exercise c/w placebo intervention or as adjunct to standard treatment
      • Effect size was significant at -1.1 (-1.5 to -0.6)
    • Exercise c/w standard treatments
      • Effect size was not significant at -0.3 (-0.7 to 0.1)
    • Aerobic and non-aerobic exercise have similar effect
  • Limitations…
  • Most studies of poor quality
  • When exercise c/w placebo/adjunct, studies were found to be heterogeneous
  • None of participants exercised alone
  • Bottom line:
  • Effectiveness of exercise in reducing sxs of depression cannot be determined because of a lack of good quality research
best evidence so far dose trial
Best Evidence (so far) – DOSE trial

Dunn et al, Am J Prev Med, 2005

  • InfoPOEMs level of evidence 1b
  • 80 adults w/ mild-moderate depression randomly assigned to 1 of 5 treatment groups
    • 7 kcal/kg/week (low dose) performed on 3 or 5 days/week
    • 17.5 kcal/kg/week (high dose) performed on 3 or 5 days/week
    • flexibility exercise control performed on 3 days/week
  • Subjects exercised individually in rooms under supervision by laboratory staff
  • Primary outcome = score on 17-item Hamilton rating scale for depression (HRSD17)
dunn et al cont d
Dunn et al (Cont’d)
  • Findings…
    • Adjusted mean HRSD17 scores at 12 weeks
      • Reduced 47% for high dose exercisers
      • Reduced 30% for low dose exercisers
      • Reduced 29% for controls
      • No main effect of exercise frequency
    • Remission rates at 12 weeks comparable to other treatments for MDD
    • NNT (for clinically relevant response) in high dose exercise = 5
    • NNT (for clinically relevant response) in 3 day/week low dose exercise = 7
  • Bottom line(s):
  • Both high & low-dose aerobic exercise are effective as monotherapy in the treatment of mild to moderate MDD
  • Exercising 3 times per week is at least as effective as 5 times per week
proposed mechanisms of effect physiological
Proposed Mechanisms of Effect – Physiological
  • Monoamine hypothesis
  • Regulation of hypothalamic-pituitary-adrenal (HPA) axis
  • Endorphin hypothesis
monoamine hypothesis
Monoamine Hypothesis
  • Exercise enhances brain aminergic synaptic transmission
  • Animal models show effects on CNS levels of noradrenaline with exercise
  • Human models show effects on plasma/urine levels of monoamines
  • Limitations:
    • Plasma data are poor estimate of CNS amine levels
hpa axis imbalance
HPA Axis Imbalance
  • HPA axis may be hyperactive in depression
  • Depressed patients have
    • Higher basal cortisol levels
    • Non-suppression of endogenous cortisol with dexamethasone administration
  • Exercise delays HPA axis response to stress (animal models)
  • Exercise-trained subjects exhibit hyposensitive HPA axis response to exercise challenge (human models)
  • Limitations:
    • Not all depressed patients exhibit HPA axis hyperactivity
endorphin hypothesis
Endorphin Hypothesis
  • Exercise leads to surge of β-endorphin
  • β-endorphins reduce pain and potentiate euphoric state
  • Unclear if β-endorphins directly alter mood state or indirectly facilitate improved mood through energy conservation during exercise
  • Limitations:
    • Same as central amine hypothesis (i.e. plasma data poor estimate of central β-endorphin levels)
proposed mechanisms of effect psychological
Proposed Mechanisms of Effect – Psychological
  • Distraction hypothesis
  • Self-efficacy theory
  • Mastery hypothesis
  • Social interaction
distraction hypothesis
Distraction Hypothesis
  • Diversion from unpleasant stimuli or painful somatic complaints leads to improved affect following exercise sessions
  • 28 yo female w/ moderate depression, ADHD, bulimia
    • “Although the exercise helps me feel connected to my body, at the same time, it is also an escape from everything that is occurring in my life at a particular time…If I am truly exerting myself, it is not possible to dwell on anything outside of the present moment. It is a mental “nap”.”
self efficacy theory
Self-Efficacy Theory
  • Confidence in one’s ability to exercise is strongly related to one’s actual ability to perform the behavior
  • Exercise poses challenging task for sedentary subject…successfully adopting regular exercise may produce improved mood and enhanced ability to handle events that challenge one’s mental health
mastery hypothesis
Mastery Hypothesis
  • Depression may result as response to loss of control over one’s body
  • Control of challenging pursuit (e.g. exercise) instills sense of independence and success
  • As exerciser gains mastery of physical skills, they may take this feeling of control into everyday life
social interaction theory
Social Interaction Theory
  • Social relationships and mutual support provided to one another by co-exercisers account for beneficial effects of exercise on mental health
  • Good, quality research is lacking
    • Lack of adequate allocation concealment
    • Subjects volunteers rather than clinical subjects
    • Few studies intent-to-treat
    • Subjects not motivated to exercise screened out
    • No true control group
  • If exercise subject to FDA approval, would NOT receive approval for treatment of depression
  • Overall long-term adherence to exercise program is poor at 50%
  • Simply suggesting/recommending that a depressed patient begin exercise often proves futile
  • When “prescribing” exercise to depressed patients, consider caveats:
    • Anticipate barriers
    • Keep expectations realistic
    • Introduce feasible plan
    • Accentuate pleasurable aspects
    • State specifics
    • Encourage adherence
  • True effectiveness of exercise in reducing symptoms of depression cannot be determined because of limitations of available research


  • Exercise may be an effective therapy for mild to moderate major depressive disorder
  • Aerobic and non-aerobic exercise appear to have similar effect
  • Exercising 3 times per week is at least as effective as 5 times per week
  • Walking or jogging at 70%-85% of maximal aerobic intensity is probably as effective as drug therapy for treating mild depression
  • Aerobic exercise at a dose consistent with ACSM/public health recommendations may be an effective treatment for mild to moderate depression
  • Blumenthal JA, Babyak MA, Moore KA, et al. Effects of exercise training on older patients with major depression. Arch Intern Med 1999;159:2349-2356.
  • Dunn AL, Trivedi MH, Kampert JB, Clark CG, Chambliss HO. Exercise treatment for depression. Efficacy and dose response. Am J Prev Med 2005;28:1-8.
  • Herman S, Blumenthal JA, Babyak M, et al. Exercise therapy for depression in middle-aged and older adults: predictors of early dropout and treatment failure. Health Psychology 2002;21(6):553-563.
  • Lawlor DA, Hopker SW. The effectiveness of exercise as an intervention in the management of depression: systematic review and meta-regression analysis of randomised controlled trials. BMJ 2001;322:1-8.
  • Brosse AL, Sheets ES, Lett HS, Blumenthal JA. Exercise and the treatment of clinical depression in adults, recent findings and future directions. Sports Med 2002;32(12):741-760.
  • Paluska SA, Schwenk TL. Physical activity and mental health, current concepts. Sports Med 2000;29(3):167-180.
  • Pollock KM. Exercise in treating depression: broadening the psychotherapist’s role. J Clin Psychol/In Session 2001;57(11):1289-1300.
  • Scully D, Kremer J, Meade MM, et al. Physical exercise and psychological well being: a critical review. Br J Sports Med 1998;32:111-120.
  • Bäckmand H, Kaprio J, Kujala U, Sarna S. Personality and mood of former elite male athletes – a descriptive study. Int J Sports Med 2001;22:215-221.
  • Bäckmand H, Kaprio J, Kujala U, Sarna S. Influence of physical activity on depression and anxiety of former elite athletes. Int J Sports Med 2003;24:609-619.
  • Dimeo F, Bauer M, Varahram I, et al. Benefits from aerobic exercise in patients with major depression: a pilot study. Br J Sports Med 2001;35:114-117.
  • Institute for Clinical Systems Improvement (ICSI). Major depression in adults in primary care. Bloomington (MN): ICSI 2004 May.
  • Kessler et al. The epidemiology of major depressive disorder. JAMA 2003;289(23):3095-3105
  • Murray CJL, Lopez AD. The global burden of disease study. Lancet 1997 May;349(9063):1436-1442.
  • Camacho TC, Roberts RE, Lazarus NB, et al. Physical activity and depression: evidence from the Alameda County Study. Am J Epidemiol 1991 Jul 15;134(2):220-231.