exercise in the treatment of depression sean t. mullendore major, usaf, mc primary care sports...

Exercise in the Treatment Exercise in the Treatment of Depressionof Depression

Sean T. MullendoreSean T. Mullendore

Major, USAF, MCMajor, USAF, MC

Primary Care Sports Medicine Primary Care Sports Medicine FellowFellow

ObjectivesObjectives

Scope of problemScope of problem Depression definedDepression defined Evidence of exercise to treat Evidence of exercise to treat

depressiondepression Proposed mechanisms of effectProposed mechanisms of effect Limitations of evidence/applicationLimitations of evidence/application Bottom lineBottom line

Scope of Problem – Scope of Problem – DepressionDepression

Prevalence between 5-10% of adults in Prevalence between 5-10% of adults in primary care in U.S.primary care in U.S.

2-3X have depressive symptoms without 2-3X have depressive symptoms without DSM-IV criteriaDSM-IV criteria

Women affected 2X as often as menWomen affected 2X as often as men Depressive disorders are 4Depressive disorders are 4thth most most

important cause of disability worldwideimportant cause of disability worldwide Mild-moderate major depressive disorder Mild-moderate major depressive disorder

ranks 2ranks 2ndnd to ischemic heart dz for years of to ischemic heart dz for years of life lost due to premature death/disabilitylife lost due to premature death/disability

Depression – Depression – Presentations/Risk FactorsPresentations/Risk Factors

Presentations:Presentations: Multiple medical visitsMultiple medical visits Multiple somatic Multiple somatic

complaintscomplaints Work/relationship Work/relationship

dysfunctiondysfunction Sleep disturbanceSleep disturbance Volunteered c/o stress Volunteered c/o stress

or mood disturbanceor mood disturbance

Risk FactorsRisk Factors Family/personal hxFamily/personal hx Chronic medical Chronic medical

illnessillness Major life changeMajor life change Stressful life Stressful life

event(s) involving event(s) involving lossloss

Depression – Screening Depression – Screening ToolsTools

SIGECAPSSIGECAPS Validated instruments as adjuncts to Validated instruments as adjuncts to

clinical interviewclinical interview Beck Depression Inventory (BDI)Beck Depression Inventory (BDI) Hamilton Rating Scale for Depression Hamilton Rating Scale for Depression

(HAM-D)(HAM-D) Quality Improvement for Depression Quality Improvement for Depression

Scale (QIDS)Scale (QIDS)

Depression DefinedDepression Defined

Diagnostic and Statistical Manual of Diagnostic and Statistical Manual of Mental Disorders, 4Mental Disorders, 4thth Edition Text Edition Text Revision (DSM-IV TR)Revision (DSM-IV TR) 5 or more symptoms present during 5 or more symptoms present during

same 2-week periodsame 2-week period At least 1 symptom eitherAt least 1 symptom either

Depressed mood ORDepressed mood OR Loss of interest/pleasureLoss of interest/pleasure

Other Disorders to Other Disorders to Consider…Consider…

DysthymiaDysthymia Adjustment disorder with depressed Adjustment disorder with depressed

moodmood Bipolar disorderBipolar disorder Substance abuseSubstance abuse Overtraining/“staleness”Overtraining/“staleness”

Descriptive & Cross-Sectional Descriptive & Cross-Sectional DataData

Camacho et al, Camacho et al, Am J EpidemiolAm J Epidemiol 1991 1991 Participant activity levels & depressive Participant activity levels & depressive

sxs measured in 1965, 1974, & 1983sxs measured in 1965, 1974, & 1983 Significant risk for depression at 1974 Significant risk for depression at 1974

follow-up if inactive at baselinefollow-up if inactive at baseline Changes in exercise habits between Changes in exercise habits between

1965-1974 may have changed risk of 1965-1974 may have changed risk of depression in 1983 (i.e. more active = depression in 1983 (i.e. more active = less depression and vice versa)less depression and vice versa)


Bäckmand et al, Bäckmand et al, Int J Sports MedInt J Sports Med, 2001, 2001 Male athletes representing Finland from Male athletes representing Finland from

1920-1965 with controls classified as 1920-1965 with controls classified as healthy at age 20healthy at age 20

5 athlete groups: endurance, 5 athlete groups: endurance, power/combat, power/individual, team, power/combat, power/individual, team, shootingshooting

Questionnaires completed in 1985 & 1995Questionnaires completed in 1985 & 1995 Finding: Referents more depressed than Finding: Referents more depressed than

endurance and team sport athletesendurance and team sport athletes


Bäckmand et al, Bäckmand et al, Int J Sports MedInt J Sports Med, 2003, 2003 Former elite male athletes surveyed by Former elite male athletes surveyed by

questionnaire in 1985 & 1995questionnaire in 1985 & 1995 Findings:Findings:

Low levels of physical activity Low levels of physical activity significantly increased risk of significantly increased risk of depressiondepression

Increase of 1 MET-unit (hour/day) Increase of 1 MET-unit (hour/day) statistically decreased risk of statistically decreased risk of depression by 8%depression by 8%

Randomized Controlled TrialRandomized Controlled Trial

Blumenthal JA et al, Blumenthal JA et al, Arch Intern MedArch Intern Med , 1999 , 1999 InfoPOEMs level of evidence 1bInfoPOEMs level of evidence 1b 156 depressed older patients randomly assigned 156 depressed older patients randomly assigned

to 1 of 3 groupsto 1 of 3 groups Supervised aerobic exercise at 70%-85% of heart rate Supervised aerobic exercise at 70%-85% of heart rate

reserve for 30 minutes on 3 days per weekreserve for 30 minutes on 3 days per week Zoloft Rx at 50 mg to 200 mg dailyZoloft Rx at 50 mg to 200 mg daily Both aerobic exercise and Zoloft RxBoth aerobic exercise and Zoloft Rx

Primary outcomes = scores on Hamilton Rating Primary outcomes = scores on Hamilton Rating Scale for Depression (HAM-D) and Beck Scale for Depression (HAM-D) and Beck Depression Inventory (BDI)Depression Inventory (BDI)

Blumenthal JA et al (Cont’d)Blumenthal JA et al (Cont’d)

Findings at 4 months…Findings at 4 months… All 3 groups achieved comparable & significant All 3 groups achieved comparable & significant

remission of MDD based on DSM-IV criteriaremission of MDD based on DSM-IV criteria 60.4% in exercise group60.4% in exercise group 68.8% in Zoloft group68.8% in Zoloft group 65.5% in exercise + Zoloft group65.5% in exercise + Zoloft group

Patients on Zoloft Rx alone responded fasterPatients on Zoloft Rx alone responded faster Among patients receiving combination tx, those Among patients receiving combination tx, those

with less severe MDD responded more quickly to with less severe MDD responded more quickly to exercise + Zoloft than those with more severe exercise + Zoloft than those with more severe MDDMDD

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 ReviewSystematic Review

Lawlor et al, Lawlor et al, BMJBMJ, 2001, 2001 Outcomes = mean differences in effect Outcomes = mean differences in effect

size in BDI score between exercise & no size in BDI score between exercise & no treatment and between exercise & treatment and between exercise & cognitive therapycognitive therapy

72 potentially relevant studies; 56 were 72 potentially relevant studies; 56 were excluded from analysisexcluded from analysis

Lawlor et al (Cont’d)Lawlor et al (Cont’d)

Findings…Findings… Exercise c/w placebo intervention or as Exercise c/w placebo intervention or as

adjunct to standard treatmentadjunct to standard treatment Effect size was significant at -1.1 (-1.5 to -0.6)Effect size was significant at -1.1 (-1.5 to -0.6)

Exercise c/w standard treatmentsExercise c/w standard treatments Effect size was not significant at -0.3 (-0.7 to Effect size was not significant at -0.3 (-0.7 to

0.1)0.1) Aerobic and non-aerobic exercise have Aerobic and non-aerobic exercise have

similar effectsimilar 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 Best Evidence (so far) – DOSE trialtrial

Dunn et al, Dunn et al, Am J Prev MedAm J Prev Med, 2005, 2005 InfoPOEMs level of evidence 1bInfoPOEMs level of evidence 1b 80 adults w/ mild-moderate depression 80 adults w/ mild-moderate depression

randomly assigned to 1 of 5 treatment groupsrandomly assigned to 1 of 5 treatment groups 7 kcal/kg/week (low dose) performed on 3 or 5 7 kcal/kg/week (low dose) performed on 3 or 5

days/weekdays/week 17.5 kcal/kg/week (high dose) performed on 3 or 5 17.5 kcal/kg/week (high dose) performed on 3 or 5

days/weekdays/week flexibility exercise control performed on 3 days/weekflexibility exercise control performed on 3 days/week

Subjects exercised individually in rooms under Subjects exercised individually in rooms under supervision by laboratory staffsupervision by laboratory staff

Primary outcome = score on 17-item Hamilton Primary outcome = score on 17-item Hamilton rating scale for depression (HRSDrating scale for depression (HRSD1717))

Dunn et al (Cont’d)Dunn et al (Cont’d)

Findings…Findings… Adjusted mean HRSDAdjusted mean HRSD1717 scores at 12 weeks scores at 12 weeks

Reduced 47% for high dose exercisersReduced 47% for high dose exercisers Reduced 30% for low dose exercisersReduced 30% for low dose exercisers Reduced 29% for controlsReduced 29% for controls No main effect of exercise frequencyNo main effect of exercise frequency

Remission rates at 12 weeks comparable to Remission rates at 12 weeks comparable to other treatments for MDDother treatments for MDD

NNT (for clinically relevant response) in high NNT (for clinically relevant response) in high dose exercise = 5dose exercise = 5

NNT (for clinically relevant response) in 3 NNT (for clinically relevant response) in 3 day/week low dose exercise = 7day/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 Proposed Mechanisms of Effect – Physiological– Physiological

Monoamine hypothesisMonoamine hypothesis Regulation of hypothalamic-pituitary-Regulation of hypothalamic-pituitary-

adrenal (HPA) axisadrenal (HPA) axis Endorphin hypothesisEndorphin hypothesis

Monoamine HypothesisMonoamine Hypothesis

Exercise enhances brain aminergic Exercise enhances brain aminergic synaptic transmissionsynaptic transmission

Animal models show effects on CNS levels Animal models show effects on CNS levels of noradrenaline with exerciseof noradrenaline with exercise

Human models show effects on Human models show effects on plasma/urine levels of monoaminesplasma/urine levels of monoamines

Limitations:Limitations: Plasma data are poor estimate of CNS amine Plasma data are poor estimate of CNS amine

levelslevels

HPA Axis ImbalanceHPA Axis Imbalance

HPA axis may be hyperactive in depressionHPA axis may be hyperactive in depression Depressed patients haveDepressed patients have

Higher basal cortisol levelsHigher basal cortisol levels Non-suppression of endogenous cortisol with Non-suppression of endogenous cortisol with

dexamethasone administrationdexamethasone administration Exercise delays HPA axis response to stress Exercise delays HPA axis response to stress

(animal models)(animal models) Exercise-trained subjects exhibit hyposensitive HPA Exercise-trained subjects exhibit hyposensitive HPA

axis response to exercise challenge (human axis response to exercise challenge (human models)models)

Limitations:Limitations: Not all depressed patients exhibit HPA axis hyperactivityNot all depressed patients exhibit HPA axis hyperactivity

Endorphin HypothesisEndorphin Hypothesis

Exercise leads to surge of Exercise leads to surge of ββ-endorphin-endorphin ββ-endorphins reduce pain and potentiate -endorphins reduce pain and potentiate

euphoric stateeuphoric state Unclear if Unclear if ββ-endorphins directly alter mood -endorphins directly alter mood

state or indirectly facilitate improved mood state or indirectly facilitate improved mood through energy conservation during exercisethrough energy conservation during exercise

Limitations:Limitations: Same as central amine hypothesis (i.e. plasma Same as central amine hypothesis (i.e. plasma

data poor estimate of central data poor estimate of central ββ-endorphin levels)-endorphin levels)

Proposed Mechanisms of Effect Proposed Mechanisms of Effect – Psychological– Psychological

Distraction hypothesisDistraction hypothesis Self-efficacy theorySelf-efficacy theory Mastery hypothesisMastery hypothesis Social interactionSocial interaction

Distraction HypothesisDistraction Hypothesis

Diversion from unpleasant stimuli or painful Diversion from unpleasant stimuli or painful somatic complaints leads to improved affect somatic complaints leads to improved affect following exercise sessionsfollowing exercise sessions

28 yo female w/ moderate depression, 28 yo female w/ moderate depression, ADHD, bulimiaADHD, bulimia ““Although the exercise helps me feel connected Although the exercise helps me feel connected

to my body, at the same time, it is also an to my body, at the same time, it is also an escape from everything that is occurring in my escape from everything that is occurring in my life at a particular time…If I am truly exerting life at a particular time…If I am truly exerting myself, it is not possible to dwell on anything myself, it is not possible to dwell on anything outside of the present moment. It is a mental outside of the present moment. It is a mental “nap”.”“nap”.”

Self-Efficacy TheorySelf-Efficacy Theory

Confidence in one’s ability to exercise is Confidence in one’s ability to exercise is strongly related to one’s actual ability to strongly related to one’s actual ability to perform the behaviorperform the behavior

Exercise poses challenging task for Exercise poses challenging task for sedentary subject…successfully sedentary subject…successfully adopting regular exercise may produce adopting regular exercise may produce improved mood and enhanced ability to improved mood and enhanced ability to handle events that challenge one’s handle events that challenge one’s mental healthmental health

Mastery HypothesisMastery Hypothesis

Depression may result as response to Depression may result as response to loss of control over one’s bodyloss of control over one’s body

Control of challenging pursuit (e.g. Control of challenging pursuit (e.g. exercise) instills sense of exercise) instills sense of independence and successindependence and success

As exerciser gains mastery of As exerciser gains mastery of physical skills, they may take this physical skills, they may take this feeling of control into everyday life feeling of control into everyday life

Social Interaction TheorySocial Interaction Theory

Social relationships and mutual Social relationships and mutual support provided to one another by support provided to one another by co-exercisers account for beneficial co-exercisers account for beneficial effects of exercise on mental healtheffects of exercise on mental health

LimitationsLimitations

Good, quality research is lackingGood, quality research is lacking Lack of adequate allocation concealmentLack of adequate allocation concealment Subjects volunteers rather than clinical subjectsSubjects volunteers rather than clinical subjects Few studies intent-to-treatFew studies intent-to-treat Subjects not motivated to exercise screened outSubjects not motivated to exercise screened out No true control groupNo true control group

If exercise subject to FDA approval, would NOT If exercise subject to FDA approval, would NOT receive approval for treatment of depressionreceive approval for treatment of depression


Overall long-term adherence to Overall long-term adherence to exercise program is poor at 50%exercise program is poor at 50%

Simply suggesting/recommending Simply suggesting/recommending that a depressed patient begin that a depressed patient begin exercise often proves futileexercise often proves futile


When “prescribing” exercise to When “prescribing” exercise to depressed patients, consider depressed patients, consider caveats:caveats: Anticipate barriersAnticipate barriers Keep expectations realisticKeep expectations realistic Introduce feasible planIntroduce feasible plan Accentuate pleasurable aspectsAccentuate pleasurable aspects State specificsState specifics Encourage adherenceEncourage adherence

SummarySummary

True effectiveness of exercise in reducing True effectiveness of exercise in reducing symptoms of depression cannot be symptoms of depression cannot be determined because of limitations of determined because of limitations of available researchavailable research

BUT…BUT…

Exercise may be an effective therapy for Exercise may be an effective therapy for mild to moderate major depressive disordermild to moderate major depressive disorder

Aerobic and non-aerobic exercise appear to Aerobic and non-aerobic exercise appear to have similar effecthave similar effect

SummarySummary

Exercising 3 times per week is at least as Exercising 3 times per week is at least as effective as 5 times per weekeffective as 5 times per week

Walking or jogging at 70%-85% of maximal Walking or jogging at 70%-85% of maximal aerobic intensity is probably as effective as aerobic intensity is probably as effective as drug therapy for treating mild depressiondrug therapy for treating mild depression

Aerobic exercise at a dose consistent with Aerobic exercise at a dose consistent with ACSM/public health recommendations may ACSM/public health recommendations may be an effective treatment for mild to be an effective treatment for mild to moderate depressionmoderate depression

ReferencesReferences1.1. Blumenthal JA, Babyak MA, Moore KA, et al. Effects of exercise Blumenthal JA, Babyak MA, Moore KA, et al. Effects of exercise

training on older patients with major depression. Arch Intern training on older patients with major depression. Arch Intern Med 1999;159:2349-2356.Med 1999;159:2349-2356.

2.2. Dunn AL, Trivedi MH, Kampert JB, Clark CG, Chambliss HO. Dunn AL, Trivedi MH, Kampert JB, Clark CG, Chambliss HO. Exercise treatment for depression. Efficacy and dose response. Exercise treatment for depression. Efficacy and dose response. Am J Prev Med 2005;28:1-8.Am J Prev Med 2005;28:1-8.

3.3. Herman S, Blumenthal JA, Babyak M, et al. Exercise therapy for Herman S, Blumenthal JA, Babyak M, et al. Exercise therapy for depression in middle-aged and older adults: predictors of early depression in middle-aged and older adults: predictors of early dropout and treatment failure. Health Psychology dropout and treatment failure. Health Psychology 2002;21(6):553-563.2002;21(6):553-563.

4.4. Lawlor DA, Hopker SW. The effectiveness of exercise as an Lawlor DA, Hopker SW. The effectiveness of exercise as an intervention in the management of depression: systematic intervention in the management of depression: systematic review and meta-regression analysis of randomised controlled review and meta-regression analysis of randomised controlled trials. BMJ 2001;322:1-8.trials. BMJ 2001;322:1-8.

ReferencesReferences

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7.7. Pollock KM. Exercise in treating depression: broadening the Pollock KM. Exercise in treating depression: broadening the psychotherapist’s role. J Clin Psychol/In Session psychotherapist’s role. J Clin Psychol/In Session 2001;57(11):1289-1300.2001;57(11):1289-1300.

8.8. Scully D, Kremer J, Meade MM, et al. Physical exercise and Scully D, Kremer J, Meade MM, et al. Physical exercise and psychological well being: a critical review. Br J Sports Med psychological well being: a critical review. Br J Sports Med 1998;32:111-120.1998;32:111-120.

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10.10. Bäckmand H, Kaprio J, Kujala U, Sarna S. Influence of Bäckmand H, Kaprio J, Kujala U, Sarna S. Influence of physical activity on depression and anxiety of former elite physical activity on depression and anxiety of former elite athletes. Int J Sports Med 2003;24:609-619.athletes. Int J Sports Med 2003;24:609-619.

11.11. Dimeo F, Bauer M, Varahram I, et al. Benefits from aerobic Dimeo F, Bauer M, Varahram I, et al. Benefits from aerobic exercise in patients with major depression: a pilot study. Br exercise in patients with major depression: a pilot study. Br J Sports Med 2001;35:114-117.J Sports Med 2001;35:114-117.

12.12. Institute for Clinical Systems Improvement (ICSI). Major Institute for Clinical Systems Improvement (ICSI). Major depression in adults in primary care. Bloomington (MN): depression in adults in primary care. Bloomington (MN): ICSI 2004 May.ICSI 2004 May.

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