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Evidence-Based Reviews

Exercise prescription: A practical, effective therapy for depression

Physical activity improves depressive symptoms and is supported by controlled clinical trials

Vol. 8, No. 6 / June 2009

Comment on this article

Mrs. S, age 44, is on leave from her job as a bank cashier because depressive symptoms interfered with her performance. At a university-based psychiatric clinic she reports feeling depressed, reduced interest in daily activities, problems with sleep onset and maintenance, inconsistent appetite, low energy, hopelessness, and decreased memory and concentration.

The resident psychiatrist diagnoses major depressive disorder (MDD) and starts Mrs. S on sertraline, 50 mg/d. The dosage is gradually titrated to 200 mg/d, and after 8 weeks she reports substantial improvement.

Mrs. S returns to her job but experiences residual low energy, lethargy, and inconsistent sleep. Her work schedule and caring for her 2 children at home prevent her from continuing weekly cognitive-behavioral therapy (CBT), but she soon notices that she feels more energetic. She reports that because of high gasoline prices she has been walking several miles daily to commute by train to work. The resident psychiatrist sees this as an opportunity to reinforce the benefits of exercise for depression.

Antidepressants alone do not adequately treat many patients with depression. In the STAR*D Project—which compared long-term outcomes of various depression treatments—only 28% to 33% of outpatients achieved remission with selective serotonin reuptake inhibitor (SSRI) monotherapy. Rates were somewhat higher with bupropion or serotonin norepinephrine reuptake inhibitor (SNRI) monotherapy, but greater benefit was obtained from augmenting SSRIs.1

Combining antidepressants with psychotherapy2 and lifestyle changes—particularly exercise—makes sense intuitively and is supported by well-designed studies:

  • The 60% of adults in the National Comorbidity Survey who said they exercised regularly reported lower rates of depression and anxiety, compared with less active adults.3
  • A meta-analysis of 11 randomized, controlled trials supports the use of exercise as an effective intervention for clinical depression.4

Box 1

How does exercise affect mood? Possible mechanisms

Elevation of endorphins in the CNS

Changes in neurotransmitters such as serotonin and norepinephrine

Increased levels of brain-derived neurotrophic factor

Reduction of serum cortisol

Elevation of body temperature

Improved self-esteem

Distraction from daily stress

Induction of a relaxed state via biofeedback

This article examines the evidence supporting exercise for treating and preventing clinical depression. We begin by addressing clinicians’ concerns about motivating depressed patients to exercise.

Overcoming barriers

Physician issues. Busy physicians often omit discussions about exercise during brief office visits. Only 34% of 9,299 patients in a population-based survey5 reported that their doctors counseled them about exercise during their most recent visits. Counseling patients does not have to be time-intensive, however. A study of the Physician-based Assessment and Counseling for Exercise (PACE) project showed that 70% of physicians could provide exercise counseling in 3 to 5 minutes, and most patients reported following their physicians’ advice.6

Highly depressed individuals are at risk to quit when they encounter barriers to exercise and to respond to difficulties with frustration and self-disappointment. Thus, depressed patients may need support and encouragement to initiate and maintain regular exercise routines.7 Set small, realistic goals for them, and discuss how to solve problems and remove barriers to increase their likelihood to exercise.

Interventions are most likely to be effective when you counsel patients about exercise as prescription and discuss exercise at each visit.8 Previously sedentary patients have shown short-term moderate increases in physical activity in response to physician counseling. In a study of 212 adults (mean age 39, 84% female), the PACE project significantly increased minutes of weekly walking.9 More than one-half (52%) of patients increased their physical activity, compared with 12% of controls whose physicians did not provide the PACE intervention.

Patient issues. Lack of time and no appropriate space to exercise are common complaints, particularly among residents of regions with long, cold winters. Some patients perceive regular exercise as monotonous or boring, and others may lack the necessary initiative because of poor physical health, fear, negative experiences, or lack of knowledge about exercising. These barriers can be pronounced in older depressed persons. In a cross-sectional study of 645 residents of Jyväskylä, Finland, those age >75 with depressive symptoms were more than twice as likely to be physically inactive as nondepressed residents.10

An intensive exercise program is not the optimal starting point for many patients. Even walking or light jogging can be an effective exercise for depressed individuals with physical limitations. For these patients, a consultation with their primary physician may be necessary if a more intensive program has to be recommended.

Exercise as monotherapy

A dose-response relationship? Various mechanisms have been suggested for the benefits of exercise in depression (Box 1). Exercise alone—without medication—may be an effective treatment for mild and in some cases moderate MDD, and aerobic exercise may reduce depressive symptoms in a dose-response relationship.11

A study of exercise in a supervised laboratory setting demonstrated this relationship in 80 adults age 20 to 45 with mild-to-moderate depressive symptoms. Subjects were randomly assigned to an exercise control group (3 days/week of flexibility exercise) or 1 of 4 aerobic exercise groups that varied in total energy expenditure (a “low dose” of 7.0 kcal/kg/week or a “public health dose” of 17.5 kcal/kg/week). The 17-item Hamilton Rating Scale for Depression (HRSD) was the primary outcome measure.

After 12 weeks, HRSD scores declined from baseline by 47% in subjects engaged in the public health dose of aerobic exercise—a significant reduction. Depressive symptoms declined by 30% in the low-dose exercisers, but this was comparable to the 29% reduction in the control group.

Comment. The effective exercise dose in this study is similar to the public health recommendation of 30 minutes of moderate-to-vigorous activity on all or most days per week (see Related Resources). Antidepressant effects have been associated with more modest physical activity, however, which may be easier to initiate and maintain for individuals with depression. The study did not find significant differences in outcomes based on the subjects’ age, gender, or exercise frequency. Nevertheless, the exercise dose may be important to produce an antidepressant effect.

An inverse relationship? Compared with occasional exercise, habitual physical activity usually is associated with greater cardiorespiratory fitness. Whether habitual activity also results in fewer depressive symptoms and greater emotional well-being remains to be seen.

A large, cross-sectional, National Institutes of Health-funded study of 5,451 men and 1,277 women12 suggests an inverse relationship between physical activity and depressive symptoms. Subjects underwent a treadmill exercise test to evaluate physical fitness. A 20-point self-report scale assessed depressive symptoms, and the General Well-Being Schedule13 was used to assess emotional well-being. Depressive symptoms were more severe in “inactive” and “insufficiently active” subjects compared with “sufficiently active” and “highly active” subjects.

On the other hand, although regular exercise may be associated with reduced depressive symptoms in the population at large, no cause-effect relationship was found in a population-based, longitudinal study of 5,952 twins.14

A prospective, randomized, controlled trial15 suggests that exercise could be an important treatment tool in patients diagnosed with MDD. The 202 adult subjects (153 women, 49 men) were randomly assigned to 1 of 4 treatments:

  • supervised exercise in a group setting
  • home-based exercise
  • antidepressant medication (sertraline, 50 to 200 mg/d)
  • placebo pills.

Patients underwent the structured clinical interview for depression and completed the HRSD. After 16 weeks, 41% of participants achieved remission, defined as no longer meeting MDD criteria and a HRSD score <8. Compared with placebo controls, patients receiving active treatments tended to have higher remission rates:

  • 45% with supervised exercise
  • 40% with home-based exercise
  • 47% with medication
  • 31% with placebo.

Comment. The placebo response rate was relatively high in this study, and antidepressant dosages might not have been optimal. These factors could explain why remission rates with supervised exercise and antidepressant medication were comparable. The study might have been more reliable if it had included a medication plus exercise arm. Patients treated in an office setting might not fare as well as these study subjects whose exercise was supervised.

Postpartum depression occurs in an estimated 13% of new mothers.16 In a controlled trial, 80 women with depression at 4 weeks postpartum were assigned to either:

  • an exercise support program (1 hour supervised exercise and 2 sessions at home each week for 3 months)
  • standard care.

Box 2

Prescribing exercise regimens for depressed patients

Most depressed patients can benefit from aerobic exercise or high-intensity progressive resistance training (PRT). Consult with your patient’s primary care physician before designing an exercise regimen. Incorporate warm-up and cool-down periods during each exercise session.

Aerobics. A 30- to 45-minute daily regimen of running, walking, swimming, biking, dancing, or elliptical training is recommended for most people. An optimum regimen achieves a target heart rate of 70% to 85% of the individual’s maximum heart rate. A goal of 40% to 50% of maximum heart rate is an appropriate goal for patients starting an exercise program. At least 10 minutes of aerobic activity is necessary to produce the desired benefit.

PRT. High-intensity progressive resistance training may be recommended in consultation with a physical therapist or certified trainer. This usually consists of 30 to 45 minutes of systematic training of various muscle groups 3 days a week. An optimal resistance of 80% of maximal load is desirable, but this may be adjusted for individual patients. Lifting weights, push-ups, sit-ups, using resistance bands, and heavy gardening may be part of this regimen.

No subjects received medication. Women in the exercise support program were less likely to have high scores on the Edinburgh Postnatal Depression Scale, compared with controls. Women who exercised also reported a greater sense of well-being. Differences between the 2 groups were not statistically significant at 4 weeks post partum but achieved significance at 5 months.17

Depressive symptoms may exacerbate fatigue in postpartum women.18 A study of 88 women with postpartum depression showed the benefits of a home-based exercise program on physical and mental fatigue.19 This finding may be important because fatigue often is associated with treatment-resistant depression and may increase the likelihood of relapse in women with postpartum depression.20

Late-life depression. Exercise can benefit the depressed elderly as well. In a 10-week randomized, controlled trial21 of volunteers age ≥60 with major or minor depression or dysthymia, progressive resistance training (PRT) significantly reduced depression, as measured by the Beck Depression Inventory (BDI) and HRSD. PRT also improved quality of life, vitality, social functioning, and emotional well-being when compared with a control group (Box 2).

A dose-response relationship of exercise for treating late-life depression was shown in a blinded, controlled trial22 of 60 community-dwelling, depressed subjects age >60. These patients were randomly assigned to high-intensity PRT, low-intensity PRT, or standard care by a general practitioner (GP). A ≥50% reduction in HRSD score was achieved by:

  • 61% of the high-intensity PRT group
  • 29% of the low-intensity PRT group
  • 21% of the GP care group.

Sleep quality improved in all participants, with the greatest relative change in the high-intensity PRT group.

Exercise vs psychotherapy. The benefits of exercise may be comparable or superior to those of cognitive or group psychotherapy.23,24 This may be good news for patients such as Mrs. S who lack time or financial resources for regular psychotherapy.

Adjunctive exercise

In depressed patients, exercise may increase the perceived quality of life when combined with medication. This was demonstrated in a randomized, 32-week naturalistic study of 30 women, age 40 to 60, with treatment-resistant MDD.25 The 10 women who received various antidepressants plus physical exercise showed significantly greater long-term improvement in depression symptoms, as measured by the HRSD and Global Assessment of Functioning (GAF) scores, compared with 20 women who received pharmacotherapy alone.26 Study limitations included the absence of a placebo arm, small sample size, and inclusion of subjects with comorbid anxiety disorders.

Group aerobic exercise programs can be an effective and feasible treatment for depression, particularly for older adults. In a controlled trial,27 156 men and women age >50 with MDD were randomly assigned to 3 groups: a program of aerobic exercise; sertraline, ≤200 mg/d; or exercise plus sertraline. HRSD and BDI scores before and after treatment were the primary outcome measures. Secondary measures included aerobic capacity, life satisfaction, self-esteem, anxiety, and dysfunctional cognitions. After 16 weeks of treatment, similar percentages of patients in each group no longer met DSM-IV-TR criteria for MDD:

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