Exercise in the Treatment of Depression

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Exercise in the Treatment of Depression

• Sean T. Mullendore
• Major, USAF, MC
• Primary Care Sports Medicine Fellow

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Dx Mild-Moderate Depression Rx Exercise 3-5X
per week. RF 8???

• Sean T. Mullendore
• Major, USAF, MC
• Primary Care Sports Medicine Fellow

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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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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

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Depression Presentations/Risk Factors

• Presentations
• 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

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Depression Screening Tools

• SIGECAPS
• Validated instruments as adjuncts to clinical
  interview
• Beck Depression Inventory (BDI)
• Hamilton Rating Scale for Depression (HAM-D)
• Quality Improvement for Depression Scale (QIDS)

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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

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Other Disorders to Consider

• Dysthymia
• Adjustment disorder with depressed mood
• Bipolar disorder
• Substance abuse
• Overtraining/staleness

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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)

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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

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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

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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)

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Blumenthal JA et al (Contd)

• 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

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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

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Lawlor et al (Contd)

• 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

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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)

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Dunn et al (Contd)

• 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

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Proposed Mechanisms of Effect Physiological

• Monoamine hypothesis
• Regulation of hypothalamic-pituitary-adrenal
  (HPA) axis
• Endorphin hypothesis

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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

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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

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Endorphin Hypothesis

• Exercise leads to surge of ß-endorphin
• ß-endorphins reduce pain and potentiate euphoric
  state
• Unclear if ß-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 ß-endorphin levels)

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Proposed Mechanisms of Effect Psychological

• Distraction hypothesis
• Self-efficacy theory
• Mastery hypothesis
• Social interaction

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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 timeIf I am truly exerting myself, it
  is not possible to dwell on anything outside of
  the present moment. It is a mental nap.

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Self-Efficacy Theory

• Confidence in ones ability to exercise is
  strongly related to ones actual ability to
  perform the behavior
• Exercise poses challenging task for sedentary
  subjectsuccessfully adopting regular exercise
  may produce improved mood and enhanced ability to
  handle events that challenge ones mental health

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Mastery Hypothesis

• Depression may result as response to loss of
  control over ones 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

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Social Interaction Theory

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

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Limitations

• 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

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Limitations

• Overall long-term adherence to exercise program
  is poor at 50
• Simply suggesting/recommending that a depressed
  patient begin exercise often proves futile

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Limitations

• When prescribing exercise to depressed
  patients, consider caveats
• Anticipate barriers
• Keep expectations realistic
• Introduce feasible plan
• Accentuate pleasurable aspects
• State specifics
• Encourage adherence

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Summary

• True effectiveness of exercise in reducing
  symptoms of depression cannot be determined
  because of limitations of available research
• BUT
• Exercise may be an effective therapy for mild to
  moderate major depressive disorder
• Aerobic and non-aerobic exercise appear to have
  similar effect

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Summary

• 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

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Questions?
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References

• Blumenthal JA, Babyak MA, Moore KA, et al.
  Effects of exercise training on older patients
  with major depression. Arch Intern Med
  19991592349-2356.
• Dunn AL, Trivedi MH, Kampert JB, Clark CG,
  Chambliss HO. Exercise treatment for depression.
  Efficacy and dose response. Am J Prev Med
  2005281-8.
• 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
  200221(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
  20013221-8.

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References

• Brosse AL, Sheets ES, Lett HS, Blumenthal JA.
  Exercise and the treatment of clinical depression
  in adults, recent findings and future directions.
  Sports Med 200232(12)741-760.
• Paluska SA, Schwenk TL. Physical activity and
  mental health, current concepts. Sports Med
  200029(3)167-180.
• Pollock KM. Exercise in treating depression
  broadening the psychotherapists role. J Clin
  Psychol/In Session 200157(11)1289-1300.
• Scully D, Kremer J, Meade MM, et al. Physical
  exercise and psychological well being a critical
  review. Br J Sports Med 199832111-120.
• Bäckmand H, Kaprio J, Kujala U, Sarna S.
  Personality and mood of former elite male
  athletes a descriptive study. Int J Sports Med
  200122215-221.

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References

• Bäckmand H, Kaprio J, Kujala U, Sarna S.
  Influence of physical activity on depression and
  anxiety of former elite athletes. Int J Sports
  Med 200324609-619.
• Dimeo F, Bauer M, Varahram I, et al. Benefits
  from aerobic exercise in patients with major
  depression a pilot study. Br J Sports Med
  200135114-117.
• 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 2003289(23)3095-3105
• Murray CJL, Lopez AD. The global burden of
  disease study. Lancet 1997 May349(9063)1436-1442
  .

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References

• Camacho TC, Roberts RE, Lazarus NB, et al.
  Physical activity and depression evidence from
  the Alameda County Study. Am J Epidemiol 1991 Jul
  15134(2)220-231.