Poster 6.66 Carroll W. Hughes, Ph.D., ABPP1, Shauna D. Dorman, B.A.1, Conrad C. Barnes1, Graham J. Emslie, M.D.1, Betsy D. Kennard, Psy.D., ABPP1, Laura DeFina, M.D.2 1University of Texas Southwestern Medical Center – Dallas, Texas, 2The Cooper Institute – Dallas, Texas
&
INTRODUCTION This R34 study (DATE, Hughes et al, 2009) evaluates the efficacy of a randomized controlled trial to test an aerobic exercise condition in comparison to a stretch condition to treat adolescent depression. There is little empirical data on the relative efficacy of different doses of exercise for the treatment of depression and other mental health problems (Dunn et al. 2005). Some studies have demonstrated mental health benefits from relatively low doses of exercise (Hansen et al., 2001), while other studies suggest relatively high doses may be necessary (Artal, 1993). DATE represents the next logical step in the study of exercise as a treatment for MDD in adolescents. As depression improves, so should psychosocial functioning (Lewinsohn, 1999). There are no randomized controlled trials of exercise in clinically depressed adolescents. This study developed a manualized supervised exercise treatment intervention, using timeintensive state-of-the-art measures of web-based training and logs, and Actical 24/7 energy monitoring (Hughes et al., 2009). We are enrolling patients who want to try a non-medication intervention to reduce or eliminate their depressive symptoms. The feasibility study provides measures of adherence, achievement of exercise goals, drop out rates, internet activity logs and the percent that complete 3 months of exercise. It also tests efficacy with the primary between groups outcome measures of the intervention’s effectiveness based on the Children’s Depression Rating Scale (CDRSR), Clinical Global Improvement (CGI-I) and Actical accelerometer data (kcal/kg/wk) treated as a continuous variable.
Age (years) Gender
Ethnicity
Socioeconomic
16.31 (SD = 0.95) Range 12 - 18 Male = 50%
CDRS-R
53 ± 6.3
Week 12 Exit Exercise Stretch 24.4 ± 3.6 25.6 ± 7.4
Female =
CGI-Severity
4.6 ± 0.5
1.4± 0.5
1.9 ± 0.9
African Amer = 20%
CGI-Improvement
NA
1.8 ± 0.4
1.9 ± 0.7
Caucasian =
53%
QIDS – Clinician
14.9 ± 2.7
4.6 ± 1.8
4.7± 4.4
Hispanic =
27%
QIDS – Self report
12.3 ± 5.8
3.1 ± 4.1
4.1 ± 2.3
Upper =
13%
QIDS – Parent
13.0 ± 4.1
4.1 ± 2.8
6.6 ± 3.1
Middle =
81%
CGAS
52.3 ± 4.6
70.7 ± 4.5
70.9 ± 8.2
Lower =
6%
FGAS
58.9 ± 9.6
71.6 ± 8.2
58.8 ± 9.4
50%
Comorbidity MDD Only = 47% Dysthymia = 15% Anxiety Disorder = 8% Behavior ADHD = 31%
Baseline
Study Findings Completers 100% Number dropouts 0 Responders 100% Adherence (12 wk Mean) 90%
60
Fig. 3 Average Heart Rate During Session
170 155 140 125 110 95 80 65
50 40
30 20 10
Exercise
Stretch
100% 0 86% 87%
Tension
Anger
Fatigue
Depression
*Vigor
1.09
1.36
1.09
1.37
1.43
Exercise Exit
.71
.82
.67
0.70
1.29
Stretch BL
1.83
1.63
2.23
2.09
1.09
Stretch Exit
0.66
0.77
.629
.738
1.81
Significance1
.001
.016
0.00
0.00
0.10
1 Significance
reported between Baseline and Exit. *Vigor is to increase as the other factors decrease.
Table 3. Psychosocial Adjustment Scales School
Friends
Anxiety
Family
Dating
Exercise BL
2.31
2.65
2.63
2.44
4.00
Exercise Exit
1.83
2.31
1.93
1.85
4.11
Stretch BL
2.45
2.62
2.38
2.52
3.50
Stretch Exit
1.29
2.40
2.00
2.14
3.36
Significance1
.002
.220
.026
.049
.956
1 Significance
reported between Baseline and Exit.
102.7 84.17
10.65
6.25
11.95
Baseline
Week 3
Week 6
Week 9
• Preliminary data suggests that exercise may be an effective intervention for adolescent depression. In this small sample NIMH R34 feasibility study, all of the subjects, except one, responded (≥ 50% reduction of CDRS) and 13/16 achieved remission (CDRS ≤ 27) within three months. These results are based on blinded clinician ratings, and weekly participant self-reports, and parent reports. Adolescents will adhere to either an exercise or stretching routine for up to three months, although it appears that they are more likely to stay with active exercise better than stretching alone. Hence, it is feasible. Adherence rates were sustained for three months with no dropouts but appeared to be declining for the stretch condition. There are good study exit satisfaction reports by both the adolescents and the parents. Continuous monitoring, structured routines, weekly assessments, use of incentives and engaging parent support may be an important part of achieving adherence to exercise interventions.
Stretch
Exercise
0 Week 12
Table 2. Profile of Mood States Exercise BL
144
Resting
Figure 1. Blinded CDRS clinician score.
METHOD Thirty (30) adolescents (aged 12−18 years) were screened to examine exercise as a nonmedication intervention for adolescents with depression. Potential participants are evaluated for diagnosis and baseline assessment. Evaluation includes a structured diagnostic interview with the Schedule for Affective Disorders and Schizophrenia for School-Age Children-Present and Lifetime version (K-SADS-PL), as well as the Clinical Global Impressions scale (CGI), the Children’s Depression Rating Scale−Revised (CDRS-R), and Quick Inventory of Depression Symptomatology Adolescent (QIDS, www.ids-qids.org). The psychosocial symptoms are evaluated through self reports of the Social Adjustment Scale (SAS, Weissman et al.,1973), Profile of Mood State-Short (POMS, Curran et al., 1995), as well as through the clinician’s diagnostic interview. Enrollment requires diagnosis of non-psychotic MDD with symptom severity of CDRS−R > 40 and global severity of CGI−S > 4. A total of 20 patients met criteria and consented to participate, with 4 currently enrolled and 16 completed. All patients are assessed weekly. Participants are randomized single-blind to either a 12-week aerobic exercise (12 kcal/kg) group (n= 10, 9 completers) or to a stretch, or non-strenuous exercise, (< 4 kcal/kg) group (n= 10, 7 completers). Activity levels and energy expenditure is obtained from ActiCal accelerometers worn by participants for the duration of the 12 weeks.
Clinical Characteristics – Depression
Demographics
CDRS Mean total score
Objective: Exercise treatment for depressed adults has been found to be effective (Dunn et al., 2005). The present study tested depressed adolescents to determine if 1) they will adhere to an exercise only intervention, and 2) if they are likely to benefit. Methods: Non-medicated outpatient adolescents with major depressive disorder, age 12-18, were enrolled in an NIMH-funded study (Hughes et al, 2009). 30 eligible patients were screened and 20 randomized to receive 12 weeks acute treatment of either aerobic exercise (12 kcal/kg; n=9) or stretch routines (< 4 kcal/kg; n=7), with periodic assessment on all study measures. All subjects were monitored on a 24hr/7day basis for 84 days (3 months) with Actical accelerometry to determine total activity, kcal energy expenditure, and adherence. Enrollment required MDD based on the K-SADS-PL, with CDRS-R > 40 and CGI-Severity > 4 and no medical illnesses that would prevent participation in physical activity. Results: Of 20 patients who entered the study to date, 16 have completed and serve as the basis for the results presented here. Based on repeated measures of weekly (QIDS-SR, & P) and blinded tri-weekly CDRS, QIDS-C, and CGI improvement ratings, responders to both exercise and stretch showed significant reduction in depression scores. After 12 weeks, 15/16 were responders (CGI-I < 2, and CDRS-R score < 28 or a greater than 50% reduction from baseline). Conclusions: Results suggest that an ongoing exercise treatment regime for adolescents is feasible, potentially effective, and may prove to be an additional useful therapeutic alternative or adjunct to antidepressant medication for pediatric depression. Source of funding: National Institutes of Mental Health, R34MH075762-01A2, Carroll W. Hughes (P.I.)
CONCLUSIONS
Table 1
Kilocalorie energy expenditure per week
ABSTRACT
Drs. Hughes, Emslie, and Kennard have received research support from National Institute of Mental Health. Dr. Hughes and Emslie have been consultants to BioBehavioral Diagnostics, Inc. Dr. Emslie has also received research support from Eli Lilly, Forest Laboratories, and Somerset; has been a consultant for Eli Lilly, Forest Laboratories, GlaxoSmithKline, Pfizer Inc., and Wyeth Pharmaceuticals; and has been on the Speakers Bureau for Forest Laboratories Inc. Presenters Dorman, Barnes, Dubreuil, and DeFina have no conflicts to report.
RESULTS Of 20 patients who entered the study to date, 16 completed and serve as the basis for the results presented here. There are equal numbers of males and females, with good ethnic representation. The findings indicate that there is good adherence to both the exercise and stretch routines. Energy expenditure was consistently higher over time for the exercise group indicating ideal separation of the Kcal energy conditions (Fig. 2). Heart rate data was collected during the sessions in the Cooper Exercise Lab for both stretch and exercise participants. The exercise participants averaged a heart rate of 144 beats/min 10.65, while the stretch participants averaged a lower heart rate at 102.7 beats/min 6.25 (Fig.3). Their baseline heart rate was 84.17 11.95. All those who began one of the conditions completed; there were no dropouts.
Psychosocial findings: As depression symptoms improved, so did psychosocial functioning. Change was most notable in areas of School, Anxiety and Family as grades improved, family arguments decreased, anxiety decreased and participants became more involved in activities. Overall child functioning, according to clinician-rated CGAS, also improved for both groups. Family functioning, as measured by the FGAS, improved for exercise group only. Treatment implications: Exercise with sufficient Kcal/kg energy expenditure may provide an effective intervention for adolescent depression, and also a useful adjunct for partial medication responders (3 in this study so far). It may prove to be an effective first intervention for individuals preferring an initial non-medication intervention. Summary and future directions: A larger scale study needs to be conducted to replicate and extend these findings for augmentation and younger participants.
Reduction of Depression Symptoms. Blinded clinician ratings, participant selfreports, and parent reports, all indicate significant reduction in depression symptoms over time. All but one responded with either a CDRS ≤ 27 or a 50% reduction in the baseline CDRS score (Fig.1). Using CDRS of 27 as the basis for remission, 13/16 achieved remission by the Week 12 Exit visit. The CGAS and FGAS scores significantly improved by Week 12 for the Exercise Group, but only the CGAS improved for the Stretch group. All 11 subjects with a 6 month followup evaluation remained remitted. Actical Monitoring Device
(Average baseline (BL) expenditure - 4653 kcal per kg per/wk)
Figure 2. Energy Expenditure (kcal per kg-1 per/wk-1)
Psychosocial Findings. Adolescent self-reports indicate an increase in psychosocial functioning as the depressive symptoms decreased. There were significant improvements in areas of school and family functioning, as well as anxiety and boredom levels. However there was no change in functioning regarding friends and dating (Table 3). School improvements were seen in attendance, work completion, grades and teacher reports. Family functioning was most noticeably reported as decreased adolescent irritability by parents. In families where the parent and/or sibling got active along with the participant, a greater improvement in family dynamics was reported. Anxiety was reported less after the intervention, as well as boredom. Many participants became more involved in clubs, teams, and other extra-curricular activities once their depression began to decrease. Reports also show a significant decrease in negative mood states such as Tension, Anger, Fatigue and Depressed Mood (Table 2). No change was reported for feeling more Active/Vigorous, even though overall activity level and energy expenditure increased (Fig. 1).
www.exerciseanddepression.org/date
REFERENCES Artal M, Sherman C. Exercise against depression. Physician and Sportsmedicine 1998; 26:46-58. Curran SL, Andrykowski MA, Studts JL. Short Form of the Profile of Mood States (POMS-SF). Psychological Assessment 1995;7(1):80-3. Dunn AL, Trivedi MH, Kampert JB, Clark CG, HO. C. Exercise treatment for depression. American Journal of Preventive Medicine 2005;28(1):1-8. Hughes CW, Trivedi MH, Cleaver J., Greer T, Emslie GJ, Kennard B, Dorman S, Bain T, Rintelmann J, Dubreuil J, Barnes C. DATE: Depressed Adolescents Treated with Exercise: Study rationale and design. Mental Health and Physical Activity 2009; 2: 76-85. Lewinsohn PM, Clarke GN. Psychosocial treatments for adolescent depression. Clinical Psychology Review 1999;19:329-42. Trivedi, M. H., Greer, T. L., Grannemann, B. D., Church, T. S., Galper, D. I.,Sunderajan, P., et al. (2006). TREAD: treatment with exercise augmentation for depression: study rationale and design. Clinical Trials, 3, 291–305. Weissman, M.M., Bothwell, S. Assessment of social adjustment by patient self-report. Archives of General Psychiatry 1973; 33(9): 1111-5.
Questions or requests for additional information may be addressed to Carroll W. Hughes, Ph.D., ABPP, (
[email protected]), Department of Psychiatry, University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, TX 75390-8589
