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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 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 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 – Screening Tools SIGECAPS Validated instruments as adjuncts to clinical interview Beck Depression Inventory (BDI) Hamilton Rating Scale for Depression (HAMD) Quality Improvement for Depression Scale (QIDS) Depression Defined Diagnostic and Statistical Manual of Mental Disorders, 4th Edition Text Revision (DSMIV TR) 5 or more symptoms present during same 2week period At least 1 symptom either Depressed mood OR Loss of interest/pleasure Other Disorders to Consider… Dysthymia Adjustment disorder with depressed mood Bipolar disorder Substance abuse Overtraining/“staleness” 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 followup if inactive at baseline Changes in exercise habits between 19651974 may have changed risk of depression in 1983 (i.e. more active = less depression and vice versa) Descriptive & Cross-Sectional Data Bäckmand et al, Int J Sports Med, 2001 Male athletes representing Finland from 19201965 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 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 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) 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 line: 65.5% in exercise + Zoloft group Bottom •Exercise – walking or jogging – at 70%-85% of Patients on Zoloft Rx alone responded faster maximum aerobic intensity is as effective as Zoloft Among patients receiving combination tx, those with therapy treating MDD more quickly to exercise lessinsevere MDDmild responded •Zoloft had a faster initial response + therapy Zoloft than those with more severe MDD than exercise in improvement of MDD symptoms 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) 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 Limitations… Bottom line:size •Most studies Effect of was poornot quality significant at -0.3 (-0.7 to 0.1) •Effectiveness of exercise in reducingstudies sxs of were •When exercise placebo/adjunct, Aerobic andc/w non-aerobic exercise have similar depression cannot be determined because of a lack found to be heterogeneous effect of good research •None of quality participants exercised alone 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) 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 Bottom line(s): Remission rates at 12 weeks comparable to other •Bothtreatments high & low-dose for MDD aerobic exercise are effective in the treatment ofdose mild to NNT as (formonotherapy clinically relevant response) in high exercise =5 moderate MDD NNT (for clinically relevant response) in 3 day/week •Exercising times per low dose3 exercise = 7week is at least as effective as 5 times per week Proposed Mechanisms of Effect – Physiological Monoamine hypothesis Regulation of hypothalamic-pituitaryadrenal (HPA) axis Endorphin 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 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 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 Distraction hypothesis Self-efficacy theory Mastery hypothesis Social interaction 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 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 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 relationships and mutual support provided to one another by co-exercisers account for beneficial effects of exercise on mental health 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 Limitations Overall long-term adherence to exercise program is poor at 50% Simply suggesting/recommending that a depressed patient begin exercise often proves futile Limitations When “prescribing” exercise to depressed patients, consider caveats: Anticipate barriers Keep expectations realistic Introduce feasible plan Accentuate pleasurable aspects State specifics Encourage adherence 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 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 References 1. 2. 3. 4. 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. References 5. 6. 7. 8. 9. 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. References 10. 11. 12. 13. 14. 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. References 15. 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.