Exercise in the Treatment of Depression

1. Exercise in the Treatment of Depression Sean T. Mullendore Major, USAF, MC Primary Care Sports Medicine Fellow

2. Objectives • Scope of problem • Depression defined • Evidence of exercise to treat depression • Proposed mechanisms of effect • Limitations of evidence/application • Bottom line

3. 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

4. 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 Depression – Presentations/Risk Factors

5. 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)

6. 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

7. Other Disorders to Consider… • Dysthymia • Adjustment disorder with depressed mood • Bipolar disorder • Substance abuse • Overtraining/“staleness”

9. 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)

10. 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

11. 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%

12. 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)

13. 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

14. 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

15. 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

16. 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)

17. 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

19. Proposed Mechanisms of Effect – Physiological • Monoamine hypothesis • Regulation of hypothalamic-pituitary-adrenal (HPA) axis • Endorphin hypothesis

20. 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

21. 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

22. 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)

23. Proposed Mechanisms of Effect – Psychological • Distraction hypothesis • Self-efficacy theory • Mastery hypothesis • Social interaction

24. 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”.”

25. 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

26. 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

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

29. 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

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

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

32. 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

33. 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

34. Questions?

35. References • 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.

36. 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 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.

37. 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 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.

38. References • 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.