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Background: Previous observational and interven- come measures included aerobic capacity, life satisfac-
tional studies have suggested that regular physical exer- tion, self-esteem, anxiety, and dysfunctional cognitions.
cise may be associated with reduced symptoms of de-
pression. However, the extent to which exercise training Results: After 16 weeks of treatment, the groups did not
may reduce depressive symptoms in older patients with differ statistically on HAM-D or BDI scores (P = .67); ad-
major depressive disorder (MDD) has not been system- justment for baseline levels of depression yielded an es-
atically evaluated. sentially identical result. Growth curve models revealed
that all groups exhibited statistically and clinically sig-
Objective: To assess the effectiveness of an aerobic ex- nificant reductions on HAM-D and BDI scores. How-
ercise program compared with standard medication (ie, ever, patients receiving medication alone exhibited the
antidepressants) for treatment of MDD in older patients, fastest initial response; among patients receiving com-
we conducted a 16-week randomized controlled trial. bination therapy, those with less severe depressive symp-
toms initially showed a more rapid response than those
Methods: One hundred fifty-six men and women with with initially more severe depressive symptoms.
MDD (age, $50 years) were assigned randomly to a
program of aerobic exercise, antidepressants (sertraline Conclusions: An exercise training program may be con-
hydrochloride), or combined exercise and medication. sidered an alternative to antidepressants for treatment of
Subjects underwent comprehensive evaluations of de- depression in older persons. Although antidepressants may
pression, including the presence and severity of MDD us- facilitate a more rapid initial therapeutic response than ex-
ing Diagnostic and Statistical Manual of Mental Disor- ercise, after 16 weeks of treatment exercise was equally
ders, Fourth Edition criteria and Hamilton Rating Scale effective in reducing depression among patients with MDD.
for Depression (HAM-D) and Beck Depression Inven-
tory (BDI) scores before and after treatment. Secondary out- Arch Intern Med. 1999;159:2349-2356
A
GING OF THE population and cations also may induce unwanted side ef-
the increased prevalence of fects that can impair patients’ quality of life
chronic diseases among and reduce compliance.9 Even among pa-
the elderly are major chal- tients who show improvement with short-
lenges facing our society term antidepressant use, there is a signifi-
and medical community. Depression is a sig- cant risk for relapse within 1 year following
nificant cause—and consequence—of dis- treatment termination.10-12
ability among older individuals. Estimates The potential use of aerobic exercise
of the prevalence of mood disorders in the as an alternative or complementary treat-
United States range from approximately 5% ment for depression has received consider-
to 10% of elderly community dwellers1,2 to able attention recently.13 Anecdotal re-
From the Departments of 18% of nursing home residents.3 Depres- ports, followed by observational and
Psychiatry and Behavioral sive symptoms are associated with the pres- interventional studies of young and middle-
Sciences (Drs Blumenthal, ence of 1 or more chronic diseases4,5 as well aged adults, suggest that aerobic exercise is
Babyak, Moore, Herman, Khatri, as disability,2 including days in bed and days superior to placebo or to no treatment14-16
Forman, Doraiswamy, and away from normal activities.5 Moreover, ma- and is better than or equal to other treat-
Krishnan and Ms Napolitano) jor depressive disorder (MDD) has been as- ments, including psychotherapy17-19 or oc-
and Medicine (Dr Waugh), sociated with a 59% increase in mortality cupational therapy,20 in reducing depres-
Duke University Medical Center, risk during a 1-year follow-up.3 sive symptoms. These studies have been
Durham, NC; the Department
of Psychology, University
The most frequently used treatment plagued by methodological problems, how-
of Colorado, Boulder for major depression is antidepressant medi- ever, including limited sample sizes, lack of
(Dr Craighead); and cation.6 Despite the development of new randomized designs, uncontrolled concur-
the Department of Psychology, and effective medications for depression, as rent therapies, failure to document exer-
University of California– many as 30% to 35% of patients do not re- cise training effects, and imprecise diagno-
San Diego (Dr Appelbaum). spond to treatment.7-9 Furthermore, medi- sis of depression. To date, only a single study
has examined the effects of exercise as a treatment for de- of exercise training.28 Other studies of older patients with
pression in a group of 30 older adults.21 Although patients medical conditions also have shown improvements of psy-
reported a significant reduction in depressive symptoms chosocial functioning as a consequence of exercise train-
measured by the Beck Depression Inventory (BDI) com- ing.29-33 Although these studies are suggestive, to our knowl-
pared with wait-list controls (subjects on a waiting list for edge the therapeutic effects of exercise on clinical depression
treatment who served as controls), the study had impor- have not been evaluated systematically.
tant limitations, including a small sample size, imprecise Our study accomplishes this goal through a com-
diagnosis of depression, brief (ie, 6-week) treatment pe- parison of exercise treatment with the current standard
riod, lack of a standardized exercise regimen, and failure intervention—antidepressant medication—in a group of
to document exercise training. older adults with MDD. We addressed the following spe-
Other studies of the effects of exercise training on older, cific questions: (1) How do the therapeutic effects of group
healthy, nondepressed adults suggest a number of poten- exercise training compare with those of antidepressant (ser-
tial psychological benefits, including improvements in cog- traline hydrochloride [Zoloft]) therapy? (2) Is there added
nitive function, mood, and sense of well-being.22-27 A pre- benefit from combining both treatment modalities? (3) Do
vious study in our laboratory found lower levels of patients with different severity levels of depressive symp-
depressive symptoms among older men following 4 months toms respond differentially to the respective treatment ap-
proaches? and (4) How do the treatments compare with of education, marital status, income, ethnic composi-
respect to the rate of change of depressive symptoms? tion, or history of recurrent depression (Table 1).
EFFECTS ON DEPRESSION
Did Not Complete Did Not Complete Did Not Complete
16-Week Study 16-Week Study 16-Week Study
All 3 groups exhibited a significant decline in depressive
7 (14.6%) 14 (26.4%) 11 (20.0%) symptoms. Figure 3 displays the mean HAM-D and BDI
Dissatisfied With Dissatisfied With Dissatisfied With scores at study entry and at 16 weeks. The treatment groups
Group Assignment Group Assignment Group Assignment
(n = 2) (n = 2) (n = 2) did not differ significantly on baseline levels of depres-
sion as measured by the HAM-D (F2,153 = 0.96; P = .39) or
Medication Adverse Dissatisfied With Dissatisfied With
Effects (n = 5) Exercise (n = 4) Exercise (n = 3) the BDI (F2,153 = 0.90; P = .40). A 1-way multivariate analy-
sis of variance revealed no statistically significant differ-
Transportation or Medication Adverse
Logistical Problems Effects (n = 5) ences among the groups on the HAM-D or the BDI (Wilks
(n = 8)
Transportation or
l4,64 = 0.98; P = .67). The ANCOVA models controlling for
Logistical Problems baseline levels of depression also did not yield any signifi-
(n = 1)
cant treatment effects with respect to the HAM-D
(F2,152 = 0.61; P = .55) or BDI (F2,152 = 1.01; P = .37).
Completed 16-Week Completed 16-Week Completed 16-Week
Study, 41 (85.4%) Study, 39 (73.6%) Study, 44 (80.0%) Finally, based on DSM-IV criteria for MDD36 and as-
suming that patients who dropped out of the study were
Figure 1. Flowchart of trial. stilldepressed,thepercentageofpatientswhowerenolonger
25
24
23 9.0
22
•
8.5
21
20 8.0
Medication Exercise Combination Medication Exercise Combination
Treatment Group Treatment Group
Figure 2. Mean aerobic capacity and exercise tolerance for each treatment group, adjusting for pretreatment levels of depression. Compared with patients in the
medication group, those in the exercise and combination groups showed significantly higher aerobic capacity (V̇O2) (left) and longer treadmill test duration (right)
after 16 weeks of treatment. Error bars represent SEs.
22 24
Before Treatment
After Treatment
18
18
HAM-D Score
BDI Score
14
12
10
6 6
Medication Exercise Combination Medication Exercise Combination
Treatment Group Treatment Group
Figure 3. Observed mean depression scores before and after treatment. All changes from pretreatment to posttreatment were statistically significant (P,.001 for
all). The treatment groups did not differ on baseline or posttreatment levels of depression. Error bars represent SEs. HAM-D indicates Hamilton Rating Scale for
Depression; BDI, Beck Depression Inventory.
classified as clinically depressed at the end of the 4-month the first few weeks) compared with patients in the other
treatment period did not differ across treatment groups groups. Also, mildly depressed patients appeared to re-
(x22 = 0.79; P = .67); 32 patients (60.4%) in the exercise spond more quickly to the combination of medication and
group, 33 (68.8%) in the medication group, and 36 (65.5%) exercise than did moderately to severely depressed pa-
in the combination group no longer met DSM-IV criteria tients. The trajectory of BDI scores (Figure 4, right) also
for MDD according to the clinician-rater who was un- varied as a function of treatment group and initial severity
aware of patients’ group status. When the additional cri- level of depression such that patients with mild depres-
teria of a HAM-D score greater than 6 was added to the sive symptoms at baseline who received combination
DSM-IV classification, the groups again did not differ therapy exhibited a more rapid response compared with
(x22 = 1.08; P = .58), with 25 patients (47.2%) in the ex- patients receiving only medication or only exercise. Sum-
ercise group, 27 (56.2%) in the medication group, and 26 maries of the growth curve analyses for the HAM-D and
(47.3%) in the combination group classified as being no BDI are given in Table 2 and Table 3, respectively.
longer clinically depressed.
ADDITIONAL PSYCHOLOGICAL VARIABLES
RATE OF TREATMENT RESPONSE
The groups did not differ at baseline on self-reported lev-
The growth curve analysis for the HAM-D revealed that the els of anxiety, self-esteem, life satisfaction, or dysfunc-
rate of treatment response (depression score as a function tional attitudes (Table 4). At 16 weeks, all groups had
of time in treatment) differed in a statistically significant improved on each of these measures, but these changes
manner (P = .02) across the treatment groups depending were not significantly different across groups.
on the initial severity of depression. This relation can be
seen best in the fitted growth curves presented in the left COMMENT
panel of Figure 4, which shows the shape of the change
in depression scores at selected values of high and low ini- The results of this study provide empirical support for
tial depression. Depressed patients in the medication group the notion that a group program of aerobic exercise is a
exhibited a more rapid initial therapeutic response (within feasible and effective treatment for depression in older
Fitted Score
14
12
10
8
6
4 2
0 1 2 3 4 6 8 12 16 0 1 2 3 4 6 8 12 16
Week Week
Figure 4. Fitted values for Hamilton Rating Scale for Depression (HAM-D) (left) and Beck Depression Inventory (BDI) (right) across 16 weeks of treatment. Values
represent the fitted scores in each treatment group for 2 selected values of baseline depression treatment (22 for moderate to severe and 16 for mild). Week 0
values represent the baseline starting points selected for this illustration and were not generated by the model. Depression ratings of mild and moderate to severe
are at baseline.
Table 2. Solution for Growth Curve Model of HAM-D* Table 3. Solution for Growth Curve Model of BDI*
*HAM-D indicates Hamilton Rating Scale for Depression; early weeks, *BDI indicates Beck Depression Inventory; early weeks, slope from week 1
slope from week 1 to week 4; later weeks, slope from week 4 to week 16. to week 4; later weeks, slope from week 4 to week 16.
†Denominator df = 984 for all tests. †Denominator df = 984 for all tests.
adults. Most patients were able to complete the exercise reduced. That exercise was equally effective as medica-
training protocol successfully. Dropout rates and adher- tion after 16 weeks of treatment is consistent with find-
ence data compare favorably with those reported in other ings of other studies of exercise training in younger de-
studies of exercise in older populations23,24,26,47 and sug- pressed adults.14,15,17,18 The magnitude of reductions in
gest that the presence of clinical depression does not pre- depression scores is also comparable to the levels achieved
clude participation in an exercise program. Moreover, ex- using sertraline in other clinical trials of depression.45,48
ercising subjects achieved small but clinically and Moreover, the changes in depressive symptoms found for
statistically significant improvements in aerobic capac- all treatments in our study are consistent with the extent
ity, which were comparable to changes observed in non- of improvements reported in more than a dozen studies of
clinical populations of older adults.28 psychosocial interventions for MDD.12,49-53 For example, in
Patients also appeared to achieve significant clinical the National Institute of Mental Health Collaborative De-
improvement with exercise training. Among the 156 pa- pression Study,53 36% of patients undergoing cognitive be-
tients who entered the trial, 60.4% of patients in the exer- havior therapy, 43% of patients undergoing interpersonal
cise condition, 68.8% of patients in the medication condi- therapy, and 42% of patients receiving medication (imip-
tion, and 65.5% of patients in the combined condition no ramine hydrochloride) were considered “recovered,” com-
longer met DSM-IV criteria for MDD. All 3 groups also pared with 47.2% undergoing exercise, 56.2% receiving
showed significant reductions on HAM-D and BDI scores, medication (sertraline), and 47.3% receiving a combina-
indicating that their clinical symptoms were significantly tion of exercise and medication in our study.