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September 2008: Exercise can be effective therapy for depression

What are the benefits of exercise therapy for depression?

How does exercise improve a patient’s mood?

How much exercise should GPs recommend to patients?

What are the benefits of exercise therapy for depression?

How does exercise improve a patient's mood?

How much exercise should GPs recommend to patients?

Exercise has been suggested as a means to lift mood for many years, and there is increasingly strong evidence for its use as a treatment for depression. Several meta-analyses have produced robust evidence that exercise is effective as a monotherapy for depression. There is also some evidence that exercise is beneficial as an adjunct to pharmacotherapy.

Depression represents the third largest disease burden on the European population, second only to coronary heart disease when measured by effect on DALYs.1 Major depressive disorder is also an independent risk factor for cardiovascular disease and exercise can reduce cardiovascular risk.2

Two large meta-analyses in 2001 and 2006 studied the effect of exercise as a primary therapy for depression in adults.3,4 They both found a significant benefit in reducing depression scores and improving outcomes compared with non-exercise controls. They also showed that exercise was as effective as cognitive behaviour therapy.

Most studies in the meta-analyses included patients with mild to moderate depression only, and some had significant methodological weaknesses.

A Cochrane review5 published in 2006 assessed the effect of exercise alone on depression in 1,191 children and young people up to 20 years of age. Exercise reduced depression scores, with a standard mean difference of -0.66. This was significant in those studies comparing exercise with inactive controls, but no benefit was seen over psychosocial interventions.

There is also some evidence that exercise provides additional benefit when combined with antidepressant drugs. A well conducted trial in 1999 allocated depressed patients to three groups: exercise, drug therapy and both.6 There was no significant difference between the three groups at initial 16-week assessment, suggesting equivalent efficacy of exercise to medication but no additional benefit when used in combination. Those treated with exercise had an average therapeutic lag of one to two weeks longer than those given antidepressants. However, the exercise group had a significantly lower relapse rate at ten months.7

Another study found a benefit of exercise therapy as an adjunct to antidepressants in 86 older people with depression.8

There is evidence that exercise is an effective therapy in all age groups. The Cochrane review showed a benefit in young people,5 and the other meta-analyses in those over 18.3,4 Smaller trials have shown benefit in older people with an average age of 649 and 71.10,11

The NICE guideline on depression recommends that ‘patients of all ages with mild depression should be advised of the benefits of following a structured and supervised exercise programme of typically up to three sessions per week of moderate duration (45 minutes to one hour) for between 10 and 12 weeks.'12

When should GPs recommend exercise?

41205348

41205349There are few conditions in which exercise is absolutely contraindicated. Recommending exercise to almost all depressed patients is likely to be of benefit and is unlikely to cause harm. See case studies,left, for examples and box 1, attached, for information on exercise referral schemes.

However, a recent survey17 found that only 2% of GPs use exercise as their first therapy for depression and only 22% as one of their first three options.

There is clear evidence for recommending exercise in several groups of patients with medical disorders, including coronary heart disease,18 heart failure,19 diabetes20 and obesity.21 Patients with many serious medical conditions are known to be at increased risk of depression,22,23 and a positive outlook may assist recovery.24,25 Exercise therapy in these patients may serve a dual role.

There are several possible biological and behavioural explanations for the effect of exercise on depression (see box 2, attached).

Type and frequency of exercise

A controlled study comparing lower (7kcal/kg/week) and higher (17.5kcal/kg/week) intensity exercise at three or five sessions per week found a significantly greater reduction in depression scores in those allocated to high compared with low intensity exercise. However, frequency of exercise appeared to make no difference.31 A further study in a group of over 60s found a benefit at 80% of maximum load compared with lower intensity exercise.32

Aerobic exercise has been used in almost all studies in this area; however, a few small studies in the 1980s found that anaerobic exercise was equivalent to aerobic exercise in treating depression.4 The exercise courses used in these studies were supervised schemes, and part of their effect may well be the support from exercise professionals. Hence, supervised exercise on prescription schemes, where available, are likely to enhance benefit.

Most exercise programmes studied in the two meta-analyses3,5 used three sessions per week. Hence, with the limited evidence available, it would be reasonable to recommend three sessions of high intensity exercise per week to most depressed patients, with the absolute intensity tailored to the individual patient, taking into account their comorbidities. An energy expenditure of 17.5kcal/kg/week equates to three sessions a week of exercising to a heart rate of 145 beats per minute for about 30 minutes.

CHD and depression

Major depressive disorder is a risk factor for cardiovascular disease,2 independent of traditional risk factors.

Several hypotheses have been proposed to explain the mechanism of this link, including impaired arterial endothelial function, overactivity of the sympathetic nervous system, platelet hyperaggregability, and abnormal folate and homocysteine metabolism. There is evidence that acute platelet hyperaggregability is treated by SSRIs,33 but cardiovascular risk nevertheless persists.

Previous depression causes endothelial dysfunction that persists despite euthymia. In one study, 12 patients with treated major depression underwent flow-mediated dilatation measurement of the brachial artery

(a commonly used assessment of endothelial function). When compared with ten matched controls with no history of depression, there was a significant impairment of arterial endothelial function.34

In a separate study, blockade of cortisol synthesis with metyrapone was found to reverse this endothelial dysfunction.35 This provides evidence for a link with depression, through hypothalamic-adrenal hyperfunction causing endothelial dysfunction, eventually leading to cardiovascular disease. Such a link suggests potential therapeutic strategies (including the use of exercise programmes) for the prevention of excess cardiovascular risk associated with depression, though further research is needed.

Conclusion

Large high quality trials are needed to confirm the effect of exercise on depression and several such trials are due to report soon.36,37 The evidence available at present suggests that exercise has a significant role in the treatment of depression.

Exercise is also of benefit in a variety of commonly coexisting clinical conditions, and hence should be recommended to the majority of patients with depressive symptoms presenting in primary care. Patients with other risk factors for cardiovascular disease are particularly likely to benefit from such an intervention, but again this needs to be confirmed in further studies.

Box 1: Exercise referral for depression – frequently asked questions Key points Authors

Dr James H P Gamble
BM BCh MA MRCP
ST2 in general medicine, Royal Berkshire Hospital, Reading

Dr Julian O M Ormerod
BM BCh MA
clinical research fellow

Professor Michael P Frenneaux
MBBS MD FACC FRCP FESC FRACP
Chair of Cardiovascular Medicine, Department of Cardiovascular Medicine, University of Birmingham

Box 2: Possible mechanisms for the effect of exercise on depression Casestudy1 Casestudy2

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