Mood treatment with antidepressants or running

Treatment with an SSRI antidepressant or exercise training have both shown
effectiveness in depression and anxiety care but are seldom compared in one
trial. Further, whether the influence of these interventions on physiological
processes and general health are comparable is unknown. The MOod Treatment with
Antidepressants or Running (MOTAR) study is a multi-center clinical trial,
partly randomized, to examine whether depression and anxiety treatment reduces
physiological stress. Four aims will be investigated: 1) Are the effects of
antidepressant treatment and exercise treatment on depression and/or anxiety
symptomatology and general health indicators comparable? 2) Is recovery of
depression and/or anxiety after treatment associated with reduced cellular
aging and metabolic stress? 3) Are antidepressants and exercise intervention
similarly effective in reducing cellular aging and metabolic stress? 4) Are
changes in depression and/or anxiety related brain activity accompanied by
changes in physiological health? 5) To what extent are physiological health
status and brain activity different in depressed/anxious patients before and
after treatment as compared to healthy controls? The study*s design is a
16-week treatment program with either SSRIs or three times per week running.
The sample consists of 240 participants with current major depressive disorder
and/or current anxiety disorder recruited in the mental health care setting.
120 participants will be randomized for treatment arm and 120 participants will
receive treatment of their preference. 30 healthy controls without lifetime
depressive and anxiety disorders will be included to compare basic
characteristics. During the baseline assessment (prior to treatment program)
written questionnaires, an interview, medical examination, blood, urine and
saliva collection and a cycle ergometer test will be taken and information will
be gathered about demographic, (mental) health outcomes, psychosocial,
clinical, biological and genetic determinants. In addition, alterations in
brain processes in a subsample of minimal 25 patients per treatment arm will be
assessed using functional MRI. Assessments will be repeated after 16 weeks of
treatment with SSRIs or exercise training and 1 year after starting treatment.
The findings of this trial are expected to provide detailed information about
the relationship between treatment of depression and/or anxiety and the
reduction of physiological stress, which contributes to a better understanding
of the biological accomplishments of the two treatment regimens.

1) Are the effects of antidepressant treatment and exercise treatment on
depression and/or anxiety symptomatology and general health indicators
comparable?
2) Is recovery of depression and/or anxiety after treatment associated with
reduced cellular aging and metabolic stress?
3) Are antidepressants and exercise intervention similarly effective in
reducing cellular aging and metabolic stress?
4) Are changes in depression and/or anxiety related brain activity accompanied
by changes in physiological health?
5) To what extent are physiological health status and brain activity different
in depressed/anxious patients before and after treatment as compared to healthy
controls?

A clinical trial, partly randomized, with 2 different conditions: SSRI
treatment or exercise therapy with also MRI techniques.

Antidepressant treatment: Subjects will receive standardized treatment with
selective serotonin reuptake inhibitor (SSRI) which has documented efficacy, a
rather favorable side effect profile, and is the most commonly prescribed
antidepressant. Medication management will be provided by a psychiatrist who
meets with each patient at study onset and weeks 2, 6, 10 and 16. At these
meetings, the psychiatrist evaluates treatment response and side effects and
titrates dosage according to the evidence-based Dutch multidisciplinary
depression/anxiety guidelines until a well-tolerated therapeutic dosage is
achieved. Adherence to treatment is evaluated by pill count.

Exercise intervention: During 16 consecutive weeks, subjects will be requested
to exercise 3 days per week for 45 minutes, following public health
recommendations by CDC/American College of Sports Medicine and its earlier
confirmed successful depression/anxiety improvement results. Participants are
gradually assigned individual training ranges equivalent to 70% to 85% of heart
rate reserve calculated from the maximum heart rate achieved during an initial
treadmill test. Exercise sessions will be organized and supervised by qualified
staff, starting with a 10-minute warm-up exercise period followed by 30 minutes
of jogging at an intensity that will maintain heart rate within the assigned
training range, finishing with 5 minutes of cool-down exercises. Routine checks
will monitor for the potential occurrence of dangerous depression/anxiety
worsening, in which case clinical referral will be sought. Subjects are
stimulated to participate in all three organized group exercise sessions per
week, but if strongly preferred they are allowed to exercise individually 1
time per week. Subjects will wear heart rate recorders during all exercise
sessions and report daily activities on an exercise log. Their data will be
uploaded after sessions and used to encourage study compliance.

Respondents will have a baseline assessment including interview,
questionnaires, cycle ergometer test, collection of blood, saliva and urine
samples during 3,5 hours. This assessment will be repeated after 16 weeks to
evaluate differences between pre- and post treatment of the depression/anxiety
(approximately 3.5 hours). After 6 and 10 weeks depressive symptoms will be
measured using a questionnaire (10 minutes per session). 1 year after the
baseline assessment a follow up will take place. Alle respondents will receive
a self report questionnaire at home (30 minutes).

Duration of MRI assessment will be 2,5 hours and will be repeated after 16
weeks of SSRI or running therapy. It includes cognitive and emotional task
inside and outside the scanner and will be taken in a subsample of 50
respondents.

No burden or risks are associated with the treatment of SSRI, exercise training
or MRI assessment.

The control group will undergo only a baseline assessment, including a MRI
assessment and will not undergo follow up assessments.