The American Journal on Addictions, 24: 246–251, 2014 Copyright © American Academy of Addiction Psychiatry ISSN: 1055-0496 print / 1521-0391 online DOI: 10.1002/ajad.12175
Predictors of Depression Outcomes Among Abstinent Methamphetamine-Dependent Individuals Exposed to an Exercise Intervention Margaret Haglund, MD,1 Alfonso Ang, PhD,2 Larissa Mooney, MD,3 Rachel Gonzales, PhD, MPH,4 Joy Chudzynski, PsyD,2 Christopher B. Cooper, MD, PhD,5 Brett A. Dolezal, PhD,5 Michael Gitlin, MD,1 Richard A. Rawson, PhD2 1
Adult Division of Psychiatry, David Geffen School of Medicine, UCLA, Los Angeles, California Integrated Substance Abuse Programs, Department of Psychiatry, David Geffen School of Medicine, UCLA, Los Angeles, California 3 Addiction Medicine Clinic, Department of Psychiatry, David Geffen School of Medicine, UCLA, Los Angeles, California 4 Azusa Pacific University, Azusa, California, and Integrated Substance Abuse Programs, Department of Psychiatry, David Geffen School of Medicine, UCLA, Los Angeles, California 5 Exercise Physiology Research Laboratory, Departments of Medicine and Physiology, David Geffen School of Medicine, UCLA, Los Angeles, California 2
Background and Objectives: This paper expands on a study investigating depression outcomes in response to an 8-week exercise intervention among methamphetamine (MA) dependent individuals in early recovery. Methods: A total of 135 MA-dependent individuals enrolled in residential treatment were randomly assigned to either a structured exercise intervention or a structured health education control group. Both groups were similar in format: 60-minute sessions, offered three times a week over an 8-week study period. Results: Results showed that at the 8-week trial endpoint, participants randomized to the exercise intervention showed significantly greater reduction in depression symptom scores than participants randomized to the health education group, and that participants who attended the greatest number of exercise sessions derived the greatest benefit. This paper further analyzes study data to uncover individual predictors of depression response to exercise and finds that among participants randomized to exercise treatment, individuals with the most severe medical, psychiatric, and addiction disease burden at baseline showed the most significant improvement in depressive symptoms by study endpoint. Conclusions: Our findings suggest that exercise in moderate dose is effective at treating depressive symptoms in individuals in early recovery from addiction, and furthermore, that treatment with exercise appears to be particularly beneficial to individuals who suffer from severe medical, psychiatric, and addictive disorders. (Am J Addict 2015;24:246–251)
Received June 29, 2014; revised September 20, 2014; accepted October 12, 2014. Address correspondence to Dr. Haglund, Adult Division of Psychiatry, 300 UCLA Medical Plaza Suite 2200, UCLA, Los Angeles, CA 90095. E-mail: [email protected] 246
INTRODUCTION Physical exercise has known efficacy in treating mood symptoms in individuals with depressive disorders, and those who exercise regularly are at lower risk of developing major depression.1 In recent years, a number of randomized controlled trials have indicated that in some cases, exercise may be as equally effective a treatment for depression as current standard-of-care psychological and pharmacological interventions.2 Studies suggest that exercise at doses equal or greater to public-health recommended levels yields the greatest benefit in terms of preventing and treating depression.3,4 However, little is known about individual characteristics that predict mood response to exercise treatment in any given patient with depression. Individuals with addictive disorders, in particular methamphetamine (MA) dependence, have high rates of clinical depression.5 In individuals with substance use disorders, concomitant depression decreases the likelihood of achieving abstinence and predicts more frequent relapses both during and after treatment.6,7 Studies have shown that among MA-dependent individuals, depressive symptoms tend to be most prominent in early recovery; the risk of relapse is therefore also thought to be particularly high in early recovery.8 Preliminary evidence published by our group suggests that, when incorporated into substance abuse treatment, physical exercise leads to significant improvement in depressive symptoms in individuals in early recovery from MA-dependence (see Rawson et al., in submission).9 This paper further investigates individual factors that predicted the
most significant depression response to exercise therapy among our sample. We examine baseline medical and psychiatric conditions (i.e., HIV status, number of prior medical and psychiatric hospitalizations) as well as baseline drug use severity (as measured by injection drug use) in order to determine whether certain individual characteristics can predict depression response to exercise treatment. Understanding who derives the greatest benefit from exercise therapy will be of value in constructing evidence-based treatments for depression in substance-dependent populations.
MATERIALS AND METHODS Participants Participants were 135 MA-dependent adults newly admitted to a residential substance abuse treatment program, who were recruited upon admission to this randomized controlled trial of exercise for the treatment of MA dependence. Inclusion criteria were MA dependence (by DSM-IV), age 18 to 55 years, ability to understand English, and ability to attend treatment. Individuals were excluded if they had medical conditions that compromised their physical safety as a participant, required medical detoxification from alcohol or other substances, or demonstrated psychiatric impairment that warranted hospitalization or primary treatment. Procedures The study treatment comprised an 8-week progressive aerobic and resistance exercise training program. Participants were randomized into one of two study conditions: exercise training (n ¼ 69) or health education (n ¼ 66), each offered 3 days a week for 60 min. Exercise sessions were supervised individually or in pairs by a trained research staff member and consisted of 5 min of warm up, 30 min of aerobic activity on a treadmill, 15 min of resistance training with weight-lifting in major muscle groups, and 5 min of cool-down and stretching. Exercise sessions were individually tailored and progressive: treadmill speed and grade and resistance weight were increased throughout the study period depending on participants’ abilities. Health education sessions were also lead by trained research staff and consisted of multimedia classes addressing a variety of wellness topics such as nutrition, sleep hygiene, time management, health screening recommendations, etc. For further details of both education and exercise treatments, see our group’s methodology paper (Mooney et al, 2014) 10. Measures Symptoms of depression were assessed using the Beck Depression Inventory (BDI), a 21-item self-report questionnaire.10 BDI total scores range from 0 to 63 and are subdivided into “minimal” (0–13), “mild” (14–19), “moderate” (20–28), and “severe” (29–63) depression. Baseline psychiatric history and drug use history were assessed using the MINI International Neuropsychiatric Interview,11 a clinician-administered structured interview based on DSM-IV criteria for psychiatric disorders, and Haglund et al.
baseline medical history was assessed with a free-form medical history questionnaire. HIV status was determined from self-report and confirmed by blood test results obtained at study entry. Statistical Analyses Mixed modeling using repeated measures regression was used to test the effects of hypothesized predictors on the primary outcome measure of depression over time (BDI scores collected at baseline and once weekly), depending on treatment condition. The intention-to-treat (ITT) population is defined as participants who were randomized and received at least one session of the 8week protocol interventions. The evaluable population is defined as the participants who are eligible to participate in the study in accordance with the inclusion and exclusion criteria and who received at least 4 weeks of the intervention (at least one session per week). Each of the primary and secondary efficacy outcome measures were analyzed for the ITT and for the evaluable population. A random effects model was used to test the main effects of treatment (dummy coded with 1 ¼ exercise, 0 ¼ education), time (in weeks), predictors (MA administration by injection), number of psychiatric and medical hospitalizations, HIV status), as well as a three-way interaction of treatment time predictor. A significant treatment time predictor interaction with a negative coefficient would indicate both that the predictor had a better outcome in the exercise group compared to the education group, and that the predictor had a better outcome within the exercise group. The effect of predictors on depression scores were compared both within exercise group and between the exercise and education groups to ensure that any effect attributed to exercise was indeed a function of active treatment and not also found in the control condition. The Hausman test was also performed to assess consistency of random effects. Normality, linearity, and heteroskedasticity checks were also performed on the data to ensure that none of the model assumptions were violated.
RESULTS Participant Characteristics There were no differences in baseline characteristics between the exercise and education groups (see Table 1). Participants’ average number of days of methamphetamine use at baseline (defined as the month prior to treatment entry) was 15.9 d (SD ¼ 9.9) for the exercise group and 16.6 d (SD ¼ 10.6) for the education group. Predictors of Depression Across Both Exercise and Education Treatment Groups Differences in BDI scores for two time points, baseline and the endpoint (Week 8), were computed among different predictors. The estimated between-group differences in BDI across the various significant predictors are shown in Table 2. Individuals who used MA in injection form had a significantly larger decrease in BDI from baseline to Week 8 than did noninjectors (BDI score decrease was larger by 2.05 points, April 2015
247
TABLE 1. Baseline participant characteristics by study condition
Exercise (n ¼ 69)
Education (n ¼ 66)
p-value
31.9 (7.4) 30.40% 12.2 (1.9) 14.50% 15.9 (9.1)
31.4 (6.5) 28.90% 12.1 (1.9) 18.20% 16.6 (10.6)
0.61 0.83 0.76 0.84 0.61
Age, (years) Females (%) Education (years) Employed (%) Methamphetamine Usea (days) Values represent mean (SD). a Self-reported for the month prior to enrollment
p ¼N.044). Larger and statistically significant decreases in BDI were also found among those who had been hospitalized for psychiatric (p ¼ .036) or medical reasons (p ¼ .035) in the past 12 months, as compared to those who had not. Those who were HIV-positive also showed greater and statistically significant decreases in BDI scores than HIV-negative participants (net decrease in BDI ¼ 2.94 points, p ¼ .038). Thus, regardless of treatment group, participants who were the most medically and psychiatrically ill at baseline, and those with the most severe addiction, had the greatest reduction in depression scores over the study period.
treatment on depression-symptom severity was found (b ¼ 0.63, p ¼ 0.001), such that by end of study, exercisegroup participants reported significantly lower BDI scores than education-group participants. Table 3 displays the predictors that had the greatest effect on depression reduction among those that received the exercise intervention. In addition, we found that participants who attended a greater number of exercise sessions during the intervention (p < .001) experienced significantly fewer depression symptoms over time. Gender, age, education, and employment status did not affect the response of mood to exercise treatment.
Predictors of Depression Outcomes in the Exercise Group Compared to the Education Group Mixed modeling using repeated measures regression was used to test for the effects of significant predictors on the primary outcome measure, BDI total score, for all eight weekly time points, including baseline. There were no significant baseline differences in depression BDI scores between the groups (13.7 for the exercise group versus 12.0 for the education group, p ¼ 0.21). A significant effect of exercise
Individual Predictors of Depression Outcomes Among Participants Randomized to Exercise Individual predictors of depression outcomes among exercise group participants were explored using mixed-effects modeling repeated measures. As shown in Table 3, the largest reduction in depressive symptoms within the exercise group was observed among MA users who used MA in injection form (b ¼ 0.53, p ¼ 0.005) and among individuals with the worst medical and psychiatric conditions at baseline, as
TABLE 2. Differences in BDI among different predictors from baseline to week 8
MA use route Baseline 8 week Change from baseline
Injection 13.92 3.33 10.59
Non-injection 11.96 3.42 8.54
Net decrease in BDI between groups p-value
2.05
0.044
Psychiatric Hospitalized (psychiatric) Not hospitalized hospitalizations, past 12 mos Baseline 14.78 9.96 8 week 3.44 2.24 Change from baseline 11.34 7.72
3.62
0.036
Medical hospitalizations, past 12 mos Baseline 8 week Change from baseline HIV Status Baseline 8 week Change from baseline 248
Hospitalized (medical)
Not hospitalized
14.23 4.78 9.45
7.63 2.3 5.33
4.12
0.035
HIV-positive 15.82 4.94 10.88
HIV-negative 9.95 2.01 7.94
2.94
0.038
Predictors of Depression Response to Exercise Treatment
April 2015
TABLE 3. Predictors of response to exercise treatment in depression outcomes across 8 weeks
Beta Coefficient MA use route—Injection Depression, baseline Psychiatric Hospitalization hx Medical Hospitalization hx HIVþ status
95% Confidence Interval
0.534 .059 0.13 0.089 0.535
(0.908, (.088, (0.258, (0.177, (0.890,
0.161) 0.029) .002) 0.002) 0.179)
p-value 0.005
Predictors of Depression Outcomes Among Abstinent Methamphetamine-Dependent Individuals Exposed to an Exercise Intervention Margaret Haglund, MD,1 Alfonso Ang, PhD,2 Larissa Mooney, MD,3 Rachel Gonzales, PhD, MPH,4 Joy Chudzynski, PsyD,2 Christopher B. Cooper, MD, PhD,5 Brett A. Dolezal, PhD,5 Michael Gitlin, MD,1 Richard A. Rawson, PhD2 1
Adult Division of Psychiatry, David Geffen School of Medicine, UCLA, Los Angeles, California Integrated Substance Abuse Programs, Department of Psychiatry, David Geffen School of Medicine, UCLA, Los Angeles, California 3 Addiction Medicine Clinic, Department of Psychiatry, David Geffen School of Medicine, UCLA, Los Angeles, California 4 Azusa Pacific University, Azusa, California, and Integrated Substance Abuse Programs, Department of Psychiatry, David Geffen School of Medicine, UCLA, Los Angeles, California 5 Exercise Physiology Research Laboratory, Departments of Medicine and Physiology, David Geffen School of Medicine, UCLA, Los Angeles, California 2
Background and Objectives: This paper expands on a study investigating depression outcomes in response to an 8-week exercise intervention among methamphetamine (MA) dependent individuals in early recovery. Methods: A total of 135 MA-dependent individuals enrolled in residential treatment were randomly assigned to either a structured exercise intervention or a structured health education control group. Both groups were similar in format: 60-minute sessions, offered three times a week over an 8-week study period. Results: Results showed that at the 8-week trial endpoint, participants randomized to the exercise intervention showed significantly greater reduction in depression symptom scores than participants randomized to the health education group, and that participants who attended the greatest number of exercise sessions derived the greatest benefit. This paper further analyzes study data to uncover individual predictors of depression response to exercise and finds that among participants randomized to exercise treatment, individuals with the most severe medical, psychiatric, and addiction disease burden at baseline showed the most significant improvement in depressive symptoms by study endpoint. Conclusions: Our findings suggest that exercise in moderate dose is effective at treating depressive symptoms in individuals in early recovery from addiction, and furthermore, that treatment with exercise appears to be particularly beneficial to individuals who suffer from severe medical, psychiatric, and addictive disorders. (Am J Addict 2015;24:246–251)
Received June 29, 2014; revised September 20, 2014; accepted October 12, 2014. Address correspondence to Dr. Haglund, Adult Division of Psychiatry, 300 UCLA Medical Plaza Suite 2200, UCLA, Los Angeles, CA 90095. E-mail: [email protected] 246
INTRODUCTION Physical exercise has known efficacy in treating mood symptoms in individuals with depressive disorders, and those who exercise regularly are at lower risk of developing major depression.1 In recent years, a number of randomized controlled trials have indicated that in some cases, exercise may be as equally effective a treatment for depression as current standard-of-care psychological and pharmacological interventions.2 Studies suggest that exercise at doses equal or greater to public-health recommended levels yields the greatest benefit in terms of preventing and treating depression.3,4 However, little is known about individual characteristics that predict mood response to exercise treatment in any given patient with depression. Individuals with addictive disorders, in particular methamphetamine (MA) dependence, have high rates of clinical depression.5 In individuals with substance use disorders, concomitant depression decreases the likelihood of achieving abstinence and predicts more frequent relapses both during and after treatment.6,7 Studies have shown that among MA-dependent individuals, depressive symptoms tend to be most prominent in early recovery; the risk of relapse is therefore also thought to be particularly high in early recovery.8 Preliminary evidence published by our group suggests that, when incorporated into substance abuse treatment, physical exercise leads to significant improvement in depressive symptoms in individuals in early recovery from MA-dependence (see Rawson et al., in submission).9 This paper further investigates individual factors that predicted the
most significant depression response to exercise therapy among our sample. We examine baseline medical and psychiatric conditions (i.e., HIV status, number of prior medical and psychiatric hospitalizations) as well as baseline drug use severity (as measured by injection drug use) in order to determine whether certain individual characteristics can predict depression response to exercise treatment. Understanding who derives the greatest benefit from exercise therapy will be of value in constructing evidence-based treatments for depression in substance-dependent populations.
MATERIALS AND METHODS Participants Participants were 135 MA-dependent adults newly admitted to a residential substance abuse treatment program, who were recruited upon admission to this randomized controlled trial of exercise for the treatment of MA dependence. Inclusion criteria were MA dependence (by DSM-IV), age 18 to 55 years, ability to understand English, and ability to attend treatment. Individuals were excluded if they had medical conditions that compromised their physical safety as a participant, required medical detoxification from alcohol or other substances, or demonstrated psychiatric impairment that warranted hospitalization or primary treatment. Procedures The study treatment comprised an 8-week progressive aerobic and resistance exercise training program. Participants were randomized into one of two study conditions: exercise training (n ¼ 69) or health education (n ¼ 66), each offered 3 days a week for 60 min. Exercise sessions were supervised individually or in pairs by a trained research staff member and consisted of 5 min of warm up, 30 min of aerobic activity on a treadmill, 15 min of resistance training with weight-lifting in major muscle groups, and 5 min of cool-down and stretching. Exercise sessions were individually tailored and progressive: treadmill speed and grade and resistance weight were increased throughout the study period depending on participants’ abilities. Health education sessions were also lead by trained research staff and consisted of multimedia classes addressing a variety of wellness topics such as nutrition, sleep hygiene, time management, health screening recommendations, etc. For further details of both education and exercise treatments, see our group’s methodology paper (Mooney et al, 2014) 10. Measures Symptoms of depression were assessed using the Beck Depression Inventory (BDI), a 21-item self-report questionnaire.10 BDI total scores range from 0 to 63 and are subdivided into “minimal” (0–13), “mild” (14–19), “moderate” (20–28), and “severe” (29–63) depression. Baseline psychiatric history and drug use history were assessed using the MINI International Neuropsychiatric Interview,11 a clinician-administered structured interview based on DSM-IV criteria for psychiatric disorders, and Haglund et al.
baseline medical history was assessed with a free-form medical history questionnaire. HIV status was determined from self-report and confirmed by blood test results obtained at study entry. Statistical Analyses Mixed modeling using repeated measures regression was used to test the effects of hypothesized predictors on the primary outcome measure of depression over time (BDI scores collected at baseline and once weekly), depending on treatment condition. The intention-to-treat (ITT) population is defined as participants who were randomized and received at least one session of the 8week protocol interventions. The evaluable population is defined as the participants who are eligible to participate in the study in accordance with the inclusion and exclusion criteria and who received at least 4 weeks of the intervention (at least one session per week). Each of the primary and secondary efficacy outcome measures were analyzed for the ITT and for the evaluable population. A random effects model was used to test the main effects of treatment (dummy coded with 1 ¼ exercise, 0 ¼ education), time (in weeks), predictors (MA administration by injection), number of psychiatric and medical hospitalizations, HIV status), as well as a three-way interaction of treatment time predictor. A significant treatment time predictor interaction with a negative coefficient would indicate both that the predictor had a better outcome in the exercise group compared to the education group, and that the predictor had a better outcome within the exercise group. The effect of predictors on depression scores were compared both within exercise group and between the exercise and education groups to ensure that any effect attributed to exercise was indeed a function of active treatment and not also found in the control condition. The Hausman test was also performed to assess consistency of random effects. Normality, linearity, and heteroskedasticity checks were also performed on the data to ensure that none of the model assumptions were violated.
RESULTS Participant Characteristics There were no differences in baseline characteristics between the exercise and education groups (see Table 1). Participants’ average number of days of methamphetamine use at baseline (defined as the month prior to treatment entry) was 15.9 d (SD ¼ 9.9) for the exercise group and 16.6 d (SD ¼ 10.6) for the education group. Predictors of Depression Across Both Exercise and Education Treatment Groups Differences in BDI scores for two time points, baseline and the endpoint (Week 8), were computed among different predictors. The estimated between-group differences in BDI across the various significant predictors are shown in Table 2. Individuals who used MA in injection form had a significantly larger decrease in BDI from baseline to Week 8 than did noninjectors (BDI score decrease was larger by 2.05 points, April 2015
247
TABLE 1. Baseline participant characteristics by study condition
Exercise (n ¼ 69)
Education (n ¼ 66)
p-value
31.9 (7.4) 30.40% 12.2 (1.9) 14.50% 15.9 (9.1)
31.4 (6.5) 28.90% 12.1 (1.9) 18.20% 16.6 (10.6)
0.61 0.83 0.76 0.84 0.61
Age, (years) Females (%) Education (years) Employed (%) Methamphetamine Usea (days) Values represent mean (SD). a Self-reported for the month prior to enrollment
p ¼N.044). Larger and statistically significant decreases in BDI were also found among those who had been hospitalized for psychiatric (p ¼ .036) or medical reasons (p ¼ .035) in the past 12 months, as compared to those who had not. Those who were HIV-positive also showed greater and statistically significant decreases in BDI scores than HIV-negative participants (net decrease in BDI ¼ 2.94 points, p ¼ .038). Thus, regardless of treatment group, participants who were the most medically and psychiatrically ill at baseline, and those with the most severe addiction, had the greatest reduction in depression scores over the study period.
treatment on depression-symptom severity was found (b ¼ 0.63, p ¼ 0.001), such that by end of study, exercisegroup participants reported significantly lower BDI scores than education-group participants. Table 3 displays the predictors that had the greatest effect on depression reduction among those that received the exercise intervention. In addition, we found that participants who attended a greater number of exercise sessions during the intervention (p < .001) experienced significantly fewer depression symptoms over time. Gender, age, education, and employment status did not affect the response of mood to exercise treatment.
Predictors of Depression Outcomes in the Exercise Group Compared to the Education Group Mixed modeling using repeated measures regression was used to test for the effects of significant predictors on the primary outcome measure, BDI total score, for all eight weekly time points, including baseline. There were no significant baseline differences in depression BDI scores between the groups (13.7 for the exercise group versus 12.0 for the education group, p ¼ 0.21). A significant effect of exercise
Individual Predictors of Depression Outcomes Among Participants Randomized to Exercise Individual predictors of depression outcomes among exercise group participants were explored using mixed-effects modeling repeated measures. As shown in Table 3, the largest reduction in depressive symptoms within the exercise group was observed among MA users who used MA in injection form (b ¼ 0.53, p ¼ 0.005) and among individuals with the worst medical and psychiatric conditions at baseline, as
TABLE 2. Differences in BDI among different predictors from baseline to week 8
MA use route Baseline 8 week Change from baseline
Injection 13.92 3.33 10.59
Non-injection 11.96 3.42 8.54
Net decrease in BDI between groups p-value
2.05
0.044
Psychiatric Hospitalized (psychiatric) Not hospitalized hospitalizations, past 12 mos Baseline 14.78 9.96 8 week 3.44 2.24 Change from baseline 11.34 7.72
3.62
0.036
Medical hospitalizations, past 12 mos Baseline 8 week Change from baseline HIV Status Baseline 8 week Change from baseline 248
Hospitalized (medical)
Not hospitalized
14.23 4.78 9.45
7.63 2.3 5.33
4.12
0.035
HIV-positive 15.82 4.94 10.88
HIV-negative 9.95 2.01 7.94
2.94
0.038
Predictors of Depression Response to Exercise Treatment
April 2015
TABLE 3. Predictors of response to exercise treatment in depression outcomes across 8 weeks
Beta Coefficient MA use route—Injection Depression, baseline Psychiatric Hospitalization hx Medical Hospitalization hx HIVþ status
95% Confidence Interval
0.534 .059 0.13 0.089 0.535
(0.908, (.088, (0.258, (0.177, (0.890,
0.161) 0.029) .002) 0.002) 0.179)
p-value 0.005
