Design paperThe DOSE study: a clinical trial to examine efficacy and dose response of exercise as treatment for depression
Section snippets
Background and aims
Depression is a prevalent illness (17% lifetime prevalence) [1] with a high cost to society (estimated $44 billion/year) [2] and to the quality of life of the individual 3, 4. The Global Burden of Disease study [5] found that in developed nations unipolar major depression ranks second behind ischemic heart disease in lost years of healthy life due to premature death or disability. Current estimates indicate that only 25% of adults suffering from depression seek treatment despite major advances
Specific objectives
There were two major objectives of the DOSE study. The first was to determine the efficacy of aerobic exercise as a sole treatment of mild to moderate MDD in participants randomized to exercise compared with an “equal contact” exercise placebo control group over a 12-week acute phase treatment. The second objective was to determine the dose-response relation between different amounts and frequencies of aerobic exercise with the reduction of depressive symptoms. We hypothesized that the active
Participant selection criteria
We recruited men and women between the ages of 20 to 45 years with mild to moderate MDD. The HRSD score for mild depression is 12 to 16 and for moderate depression 17 to 25 [17]. The choice of age group was made for both scientific and practical reasons. The scientific literature suggests that MDD usually begins when individuals are 20 to 30 years of age, although it can begin at any age [18]. Also, visit rates to psychiatrists are the highest for the 20- to 40-year age group, and the
Primary outcomes
The HRSD-17 (17 items) is a clinician-rated measure designed to assess the severity of depression by assessing both the intensity and frequency of depressive symptoms. This is the most widely used measure of depression severity for clinical trials research. One review published in 1996 reported it was used in 500 published studies over a 10-year period [21], using the Cronbach α=0.88 for internal consistency. Others have found the HRSD to be correlated with psychiatrists' global rating (r
Trial design
The design of this study was a 2×2 factorial design with an exercise placebo as the control group. The two exercise factors manipulated in this design were total weekly energy expenditure per kilogram of body weight (7 kcal/kg/week and 17.5 kcal/kg/week) and frequency of exercise (3 days/week or 5 days/week). Therefore, for a 70-kg person, the total weekly energy expenditure would be 490 kcal/week if he or she received the 7 kcal/kg/week dose or 1225 kcal if he or she received the 17.5
Recruitment and screening procedures
We used a combination of recruitment techniques based, in part, on recommendations from The Cooper Institute Community Advisory Board. This included media stories on television and in the newspaper, mass mailings, letters to churches and physicians, community health fairs, and flyers distributed to businesses such as grocery stores, libraries, and apartment buildings.
Size of the trial and statistical power
We anticipated that HRSD-17 scores at baseline would have a mean of 20 points and standard deviation of seven points 49, 50, 51, 52, 53. Clinically meaningful and important treatment effects would reduce HRSD scores ⩾50%, a score of ten or less. Without preliminary data for within-individual correlation of HRSD scores pre- and postintervention, statistical power was conservatively based on comparing postintervention scores. Power for comparing active treatments with control was based on the
First 12 weeks: supervised exercise
Following randomization, all participants exercised under supervision at our laboratory for the first 12 weeks of the treatment study. Weight (kg) was collected weekly to calculate the weekly exercise dose. Participants were allowed to use a treadmill (Technogym RUNRACE) or stationary bicycle (Technogym BIKERACE) and wore a Polar Vantage XL heart- rate monitor during each exercise session. Data from the heart-rate monitor were downloaded into the exercise database. If participants used the
Data collection
Table 2 shows a summary of all data collection and time points for the DOSE study beginning with the telephone prescreen.
Data management and quality control
The data management group at The Cooper Institute oversees all data collection. Manually entered data was double-keyed and verified for accuracy, using on-screen database forms that match the format of paper forms, programmed with appropriate skip patterns and range and logic checks. Scannable data forms were reviewed prior to processing to ensure marks were clear and dark
Plans for statistical analyses
To assess the effectiveness of randomization, we will tabulate mean baseline levels of the HRSD and IDS scores among randomized participants by treatment assignment, along with age, gender, body mass index (BMI), energy expenditure, resting heart rate, blood pressures, predicted exercise capacity, medical history, and psychosocial measures. Characteristics of randomized participants who refuse treatment, drop out before completing acute-phase treatment, or complete treatment will be tabulated
Discussion
The DOSE study is the first study to our knowledge to manipulate the dose of exercise in a group of participants stringently diagnosed with mild to moderate MDD. The high internal validity of the study will allow us to assess whether exercise could be an efficacious treatment for these individuals and to identify what dose of exercise is necessary for treatment. Randomization of participants started in August 1998, and treatments were completed in October 2001. The recruitment to randomization
Acknowledgements
Participating institutions: The Cooper Institute, Dallas, Texas, USA; The University of Texas Southwestern Medical Center Depression and Anxiety Disorders Program, Dallas, Texas, USA. Steering Committee: Andrea L. Dunn, Madhukar H. Trivedi, Heather O. Chambliss.
We wish to thank participants in the DOSE study; The Cooper Institute Scientific Advisory Board: Claude Bouchard, William L. Haskell, Norman M. Kaplan, I-Min Lee, Kiang Liu, Guy S. Parcel; The Cooper Institute Community Advisory Board:
References (58)
- et al.
Global mortality, disability, and the contribution of risk factorsglobal burden of disease study
Lancet
(1997) - et al.
Running as treatment for depression
Compr Psychiatry
(1979) - et al.
Aerobic exercise as a treatment for depression in women
Behav Ther
(1983) - et al.
Predictors of adoption and maintenance of physical activity in a community sample
Prev Med
(1986) - et al.
Screening for depression in well older adultsevaluation of a short form of the CES-D
Am J Prev Med
(1994) - et al.
The Hamilton Depression Rating Scale (HDRS)changes in scores as a function of training and version used
J Affect Disord
(1991) - et al.
A new validation of the Hamilton Rating Scale for Depression
J Psychiatr Res
(1988) - et al.
Lifetime and 12-month prevalence of DSM-III-R psychiatric disorders in the United Statesresults from the National Comorbidity Survey
Arch Gen Psychiatry
(1994) - et al.
The clinical and financial burden of mood disorderscost and outcome
Psychosomatics
(1995) Mental disordersquality of life and inequality of insurance coverage
JAMA
(1995)
Health-related quality of life in primary care patients with mental disorders. Results from the PRIME-MD 1000 Study
JAMA
The risks of exercisea public health view of injuries and hazards
Public Health Rep
Effects of aerobic exercise on depressiona controlled study
Br Med J (Clin Res Ed)
Aerobic exercise and cognitive therapy in the treatment of dysphoric moods
Cognitive Therapy Res
Exercise and depression in the older adult
Nutrition in Clinical Care
The effect of exercise on clinical depression and depression resulting from mental illnessa meta-analysis
J Sport Exerc Psych
Effects of exercise training on older patients with major depression
Arch Intern Med
Conceptualization and rationale for consensus definitions of terms in major depressive disorder. Remission, recovery, relapse, and recurrence
Arch Gen Psychiatry
Office visits to psychiatristsUnited States 1989–90
Advance Data (from Vital and Health Statistics of the CDC)
The Hamilton Rating Scale for Depression
BDI-II manual
The Inventory of Depressive Symptomatology (IDS)psychometric properties
Psychol Med
Accuracy of five electronic pedometers for measuring distance walked
Med Sci Sports Exerc
Cited by (83)
Use of exercise for the therapeutic management of adult's major depressive disorder
2022, Annales Medico-PsychologiquesExercise more efficiently regulates the maturation of newborn neurons and synaptic plasticity than fluoxetine in a CUS-induced depression mouse model
2022, Experimental NeurologyCitation Excerpt :Blumenthal et al. found that the efficacy of exercise is generally comparable to that of antidepressant medications in patients with MDD (Blumenthal et al., 2007). However, the latency to onset of the antidepressant effects of exercise is still controversial (Dunn et al., 2002; Paolucci et al., 2018; Li et al., 2021). Therefore, we designed the present experiment to compare the onset of the antidepressant effects of exercise (treadmill running) and a classic antidepressant drug (fluoxetine).
Do exercise trials for adults with depression account for comorbid anxiety? A systematic review
2020, Mental Health and Physical ActivityExercise improves depressive symptoms by increasing the number of excitatory synapses in the hippocampus of CUS-Induced depression model rats
2019, Behavioural Brain ResearchCitation Excerpt :Second, differences in the exercise protocol may result in inconsistent results. Dunn et al. believed that the type, frequency, amount and duration of exercise could have different effects on the treatment of patients with depression [62]. Previous studies have found that acute, intense exercise overactivated the hypothalamic-pituitary-adrenal (HPA) axis and exacerbated depressive symptoms [26,27], but moderate-intensity exercise could help alleviate the negative effects of stress [28].
Exercise is an effective treatment for positive valence symptoms in major depression
2017, Journal of Affective DisordersPsychopharmacological Treatment for Depression in Children and Adolescents: Promoting Recovery and Resilience
2016, Positive Mental Health, Fighting Stigma and Promoting Resiliency for Children and Adolescents