The STRIDE Weight Loss and Lifestyle Intervention for Individuals Taking Antipsychotic Medications: A Randomized Trial
Publication: American Journal of Psychiatry
Abstract
Objectives:
The STRIDE study assessed whether a lifestyle intervention, tailored for individuals with serious mental illnesses, reduced weight and diabetes risk. The authors hypothesized that the STRIDE intervention would be more effective than usual care in reducing weight and improving glucose metabolism.
Method:
The study design was a multisite, parallel two-arm randomized controlled trial in community settings and an integrated health plan. Participants who met inclusion criteria were ≥18 years old, were taking antipsychotic agents for ≥30 days, and had a body mass index ≥27. Exclusions were significant cognitive impairment, pregnancy/breastfeeding, recent psychiatric hospitalization, bariatric surgery, cancer, heart attack, or stroke. The intervention emphasized moderate caloric reduction, the DASH (Dietary Approaches to Stop Hypertension) diet, and physical activity. Blinded staff collected data at baseline, 6 months, and 12 months.
Results:
Participants (men, N=56; women, N=144; mean age=47.2 years [SD=10.6]) were randomly assigned to usual care (N=96) or a 6-month weekly group intervention plus six monthly maintenance sessions (N=104). A total of 181 participants (90.5%) completed 6-month assessments, and 170 (85%) completed 12-month assessments, without differential attrition. Participants attended 14.5 of 24 sessions over 6 months. Intent-to-treat analyses revealed that intervention participants lost 4.4 kg more than control participants from baseline to 6 months (95% CI=–6.96 kg to –1.78 kg) and 2.6 kg more than control participants from baseline to 12 months (95% CI=–5.14 kg to –0.07 kg). At 12 months, fasting glucose levels in the control group had increased from 106.0 mg/dL to 109.5 mg/dL and decreased in the intervention group from 106.3 mg/dL to 100.4 mg/dL. No serious adverse events were study-related; medical hospitalizations were reduced in the intervention group (6.7%) compared with the control group (18.8%).
Conclusions:
Individuals taking antipsychotic medications can lose weight and improve fasting glucose levels. Increasing reach of the intervention is an important future step.
Individuals with serious mental illnesses are at high risk for common medical comorbidities and metabolic disturbances that lead to early morbidity and mortality (1–3) and are attributable to obesity-related conditions and risk factors (1, 4, 5). Additional contributing factors include metabolic consequences of antipsychotic medications (6, 7), limited access to medical care (8), poor nutrition (9), hyperlipidemia (10), sedentary lifestyles (5), smoking (11), and substance abuse (12).
Lifestyle-modification programs (13, 14) are the basis for recent efforts to assist individuals with serious mental illnesses in improving health and reducing cardiometabolic risks (15, 16). These programs apply behavioral approaches to weight loss and management, including education and behavioral self-management skills (17). While most of these programs focus on weight loss, reductions have typically been modest (16). We are unaware of programs that have effectively reduced diabetes risk among people with serious mental illnesses. Given the burden of medical morbidity and premature mortality in this group, methods for reducing obesity and cardiometabolic risk factors are urgently needed.
We evaluated a comprehensive lifestyle intervention (STRIDE) for individuals taking antipsychotic medications. STRIDE was based on the PREMIER lifestyle intervention with the DASH (Dietary Approaches to Stop Hypertension) dietary pattern (18–24), both developed for people without mental illnesses. PREMIER successfully reduces weight and blood pressure (25), and the DASH diet can increase high-density lipoprotein cholesterol, lower triglycerides, reduce fasting blood glucose levels, and improve insulin resistance (23, 26). We hypothesized that the STRIDE intervention would be more effective than usual care in reducing weight and improving glucose metabolism.
Method
Study Design
STRIDE was a multisite, parallel two-arm (balanced 1:1) randomized controlled trial implemented in community mental health centers and a not-for-profit integrated health plan. A description of the protocol is available elsewhere (27). The core intervention components in STRIDE are summarized in Table 1.
| Increasing awareness through monitoring: diet, physical activity, and sleep |
|---|
| Creating personalized diet and physical activity plans |
| Reducing calories |
| Reducing portion sizes, identifying and choosing alternative foods, modifying meals |
| Increasing consumption of fruits, vegetables, fiber, and low-fat dairy products |
| Increasing physical activity |
| Developing action plans for high-risk eating situations |
| Graphing progress and making adjustments |
| Addressing mental health effects on lifestyle-change efforts |
We included adults (age ≥18) taking antipsychotic agents for ≥30 days prior to enrollment and with a body mass index (BMI) ≥27. Planned BMI inclusion criteria (>25 to <45) were adjusted after pilot results (24) and following safety consultations with clinicians after individuals with a BMI over 44.9 asked to participate. Study exclusion criteria included current or currently planning pregnancy/breastfeeding, inpatient psychiatric hospitalization within ≤30 days (deferred participation was allowed), history of or currently planning bariatric surgery, history of cancer (past 2 years), heart attack or stroke within 6 months, and cognitive impairment that might interfere with consenting/participation.
All sites and procedures were reviewed, approved, and monitored by the Kaiser Permanente Northwest Institutional Review Board.
Settings
The study took place in Pacific Northwest community mental health centers (Cascadia Behavioral Healthcare and LifeWorks Northwest) and a not-for-profit integrated health system (Kaiser Permanente Northwest). All settings provide comprehensive mental health and addiction treatment; Kaiser Permanente Northwest also provides medical care. Most individuals served by Cascadia and LifeWorks are low-income. The membership of Kaiser Permanente Northwest is insured and demographically representative of the surrounding metropolitan area.
Recruitment, Screening, and Randomization
Recruitment began in July 2009 and ended in August 2011; the trial ended when follow-up visits were completed in October 2013. Using electronic medical records at two sites (Kaiser Permanente Northwest and Cascadia) and clinician referral at LifeWorks, we identified potential participants based on medication use, diagnoses, and BMI (when available). We sent letters for each potential participant to primary care or psychiatry providers to review for suitability/safety and to cosign if participation was deemed appropriate. Staff mailed the recruitment letters and telephoned potential participants to answer questions and conduct a brief screening. Eligible participants were scheduled for full screening and orientation.
Potential participants attended a group orientation session and consented to height and weight measurements. Staff reviewed inclusion criteria to ensure eligibility before requesting full written consent. The second visit included a fasting blood sample, blood pressure and waist circumference measurement, and randomization.
Participants were assigned to intervention or usual care using a stratified blocked (on gender and BMI [27–34.9 and ≥35]) randomization procedure within sites. We used computer- and paper-based randomization systems; the sequence was generated by one of us (N.A.P.). Staff not involved in data collection informed participants about randomization. Others were blinded to assignment, and participants were routinely reminded not to discuss assignment during assessments. Usual care participants were free to pursue alternative weight-loss efforts.
Staff informed participants of blood pressure and laboratory results and referred them to primary care if results were outside normal ranges. If results indicated immediate danger, participants were instructed to go to urgent care or visit clinicians immediately. At baseline, 31 participants (15.5%) were referred for blood pressure above 120 mmHg systolic or 80 mmHg diastolic (urgent: systolic ≥220 mmHg or diastolic ≥120 mmHg); 89 (44.5%) were referred for triglyceride levels >150 (urgent: >400); 44 (22%) were referred for fasting glucose levels ≥100 (urgent: >125 without diabetes mellitus diagnosis or >300 with diagnosis); and 35 (17.5%) for cholesterol levels >200. No cholesterol levels were considered urgent.
Intervention
We based STRIDE on the PREMIER lifestyle intervention with the DASH diet (19, 21), and guidelines for obesity treatment for individuals at risk for cardiovascular disease (13). STRIDE was designed to reduce weight and obesity-related risks through dietary changes, moderate calorie restriction, and increased energy expenditure through moderate physical activity. The goal was weight loss of 4.5 kg–6.8 kg (10–15 pounds) over 6 months. Adaptations made to tailor intervention content and implementation approaches for people with serious mental illnesses included using two facilitators (mental health counselor and nutritional interventionist) and managing cognitive barriers by using repetition, multiple teaching modalities (e.g., verbal, visual), skill building exercises, and practice assignments and tying materials to mental health. Added sessions addressed effects of psychiatric medications on weight, planning for psychiatric symptom exacerbation, improving sleep, eating healthfully on a budget, and stress management. We also increased tailoring for individual and group needs and case management (28). Intervention materials are available for download (http://www.kpchr.org/stridepublic/).
Initial intervention.
STRIDE’s core was a series of weekly 2-hour group meetings with 20 minutes of physical activity, delivered over 6 months. Participants were taught to keep records of 1) food, beverages, and calories consumed; 2) servings of fruits, vegetables, and low-fat dairy products; 3) fiber and fat intake; 4) daily minutes exercised; and 5) nightly hours slept. Goals included ≥25 minutes of moderate physical activity per day, primarily through walking; increased fruit, vegetable, and low-fat dairy consumption; and improved sleep quality. Food and other monitoring records were used to assess progress and identify barriers to lifestyle change. Interventionists reviewed records to help participants evaluate and modify goals and plans. Participants received a workbook to guide them with their calorie, fat, and carbohydrate content (29) and a resistance band for strength training. The intervention relied on engaging sessions and small-group activities to facilitate acquisition and practice of behavioral self-management and problem-solving skills and to foster social support and program ownership. Core components included increasing awareness of health-related practices through self-monitoring, creating personalized plans, reducing energy intake by reducing portions, increasing consumption of low-calorie density foods, increasing physical activity, managing high-risk eating situations, graphing progress, and addressing effects of mental health on change efforts.
Maintenance intervention.
The maintenance phase included 6 months of group sessions focused on maintaining weight loss through problem solving and motivational enhancement. Sessions were supplemented with monthly individual telephone sessions with group leaders. Contacts were collaborative, discussed lifestyle change efforts, and included guided problem solving.
Assessment, Data Collection, and Measurement
Blinded staff collected assessment data at baseline, at 6 months, and at 12 months. Height was measured to the nearest 0.1 cm (at baseline only) and weight to the nearest 0.1 kg; BMI was calculated using the Quetelet index (kg/m2). Blood samples were collected after a minimum 8-hour fast (we used reminder postcards and telephone calls, then questioned participants about consumption prior to obtaining samples). Those not fasting were rescheduled. Fasting tests included insulin, plasma glucose, triglycerides, and cholesterol. Blood pressure was measured after a 5-minute rest period and again after an additional 30-second rest. Measurement protocols and questionnaires are described elsewhere (27).
Statistical Analyses
We examined distributions for outcomes to determine whether transformations or different models were needed. We used generalized estimating equations (30) for primary analyses because they allow estimation of population-averaged models in repeated-measures data. Time was dummy coded, and models were run switching the reference category from baseline (first model) to 6 months (second model) to obtain effect estimates for each period. Control compared with intervention interaction terms assessed changes between groups over time; Wald tests determined whether joint effects of time-by-group equaled zero (omnibus tests for interactions). Age and study site were included as time-invariant covariates; time-varying covariates included whether or not outcome-related medications were being taken at a given time (tables of medications included in the analyses are presented in the data supplement accompanying the online version of this article). We used generalized estimating equations models with a normal distribution and identity link; the working covariance matrix was specified as exchangeable. We report covariate-adjusted results using robust estimates of standard errors (unadjusted results are summarized in the online data supplement ).
We conducted sensitivity analyses for each outcome using transformations that improved the normality of the outcome, a different family and link (e.g., negative binomial with log link) where appropriate, and unstructured working covariance matrices. For time-varying covariates, we also ran models that specified them as time-invariant (i.e., at baseline only). In most cases, there were no substantive differences among models, as reported below. Covariates in all analyses included age, site, medications known to affect outcomes, and treatment referral.
We examined between-group differences for percentage weight change, proportion of participants at or below baseline weight, proportion of participants who lost at least 5% or 10% of baseline weight, and proportion of participants who had fasting glucose values <100. In contrast to other analyses, these were not intent-to-treat results because computations require complete data to compute change scores. We then tested differences in percentage of weight change between the intervention and control groups using one-way analyses of covariance and used multiple logistic regression to test whether the proportion of participants at or below baseline weight at follow-up differed between the two groups. We also examined Pearson correlations between attendance, food and sleep logs kept, and weight and glucose change at 6 months for participants with complete data.
Sample Size
Using effect-size estimates based on PREMIER (25), a two-tailed alpha level of 0.05, and a target sample size of 252 participants, we estimated a 96% power to detect a time-by-group effect on weight at 6 months and 87% power at 12 months (27). We experienced recruitment difficulties, including one community mental health center that significantly downsized, and lack of interest in physical health among some patients and providers (28), resulting in 200 enrolled participants. Using the same a priori effect-size estimates, 200 participants provided 91% power to detect a weight change at 6 months and 77% power to detect change at 12 months.
Results
Participants
Research project staff sent 1,886 letters to potential participants, followed with telephone calls. The most common reasons for refusal were lack of interest in weight loss, scheduling conflicts, or perceptions that the intervention required too much time. The most common reasons for ineligibility were BMI below threshold or not taking antipsychotic medications. A total of 408 (21.6%) passed a preliminary eligibility screen and scheduled an orientation/screening visit, and 253 (62%) attended. Of these, 202 completed both screening visits, and 200 individuals aged ≥18 (mean age=47.2 years [SD=10.6]) were enrolled and randomly assigned: 96 to usual care and 104 to intervention (56 men and 144 women). The participant flow is presented in Figure 1. Participants’ demographic and descriptive characteristics are summarized in Table 2.
FIGURE 1. Study Flow and Full Disposition of Potential and Randomly Assigned Participantsa
a Abbreviations: SV1=screening visit 1; SV2=screening visit 2; UC=usual care.
| Characteristic | Total (N=200) | Intervention Group (N=104) | Control Group (N=96) | |||
|---|---|---|---|---|---|---|
| Mean | SD | Mean | SD | Mean | SD | |
| Age (years) | 47.2 | 10.6 | 46.2 | 11.4 | 48.3 | 9.7 |
| Weight (kg) | 107.7 | 25.1 | 108.6 | 27.2 | 106.6 | 22.7 |
| Body mass index | 38.3 | 8.3 | 38.3 | 9.1 | 38.2 | 7.3 |
| Female waist circumference (cm) | 114.5 | 19.2 | 114.6 | 20.5 | 114.4 | 17.7 |
| Male waist circumference (cm) | 112.4 | 17.5 | 113.8 | 19.6 | 110.9 | 15.1 |
| Systolic blood pressure (mmHg) | 119.2 | 14.7 | 117.5 | 14.2 | 121.0 | 15.2 |
| Diastolic blood pressure (mmHg) | 79.4 | 10.1 | 78.5 | 9.7 | 80.4 | 10.5 |
| Fasting triglycerides (mg/dL) | 188.0 | 138.6 | 188.0 | 130.3 | 188.0 | 147.8 |
| Fasting low-density lipoprotein (mg/dL) | 101.4 | 32.9 | 101.4 | 31.3 | 101.4 | 34.7 |
| Fasting high-density lipoprotein (mg/dL) | 45.8 | 12.7 | 46.6 | 14.0 | 45.0 | 11.0 |
| Fasting total cholesterol (mg/dL) | 181.6 | 39.7 | 183.2 | 38.7 | 179.9 | 40.9 |
| Fasting plasma glucose (mg/dL) | 108.9 | 32.5 | 107.6 | 31.2 | 110.3 | 34.1 |
| Fasting insulin (μU/mL) | 13.0 | 11.9 | 11.2 | 7.8 | 15.1 | 15.0 |
| Number of psychiatric medications | 3.2 | 1.5 | 3.1 | 1.4 | 3.3 | 1.5 |
| Modified Colorado Symptom Index score | 19.3 | 11.4 | 18.3 | 11.2 | 20.4 | 11.6 |
| Behavior and Symptom Identification Scale-24 item score | 1.37 | 0.68 | 1.29 | 0.70 | 1.47 | 0.64 |
| Short-Form 36 Health Survey, Version 2.0, general health item score | 42.08 | 9.99 | 42.79 | 10.94 | 41.33 | 8.84 |
| N | % | N | % | N | % | |
| Female sex | 144 | 72.0 | 75 | 72.1 | 69 | 71.9 |
| Race/ethnicity | ||||||
| White | 174 | 87.7 | 90 | 88.2 | 81 | 87.1 |
| Nonwhite | 26 | 12.3 | 12 | 11.8 | 12 | 12.9 |
| Hispanic | 4 | 2.0 | 3 | 2.9 | 1 | 1.1 |
| Education level | ||||||
| Less than high school diploma/GED | 15 | 7.5 | 6 | 5.8 | 9 | 9.4 |
| High school graduate/GED | 46 | 23.0 | 26 | 25.0 | 20 | 20.8 |
| Some college | 87 | 43.5 | 44 | 42.3 | 43 | 44.8 |
| College graduate | 52 | 26.0 | 28 | 26.9 | 24 | 25.0 |
| Never married | 57 | 28.5 | 37 | 35.6 | 20 | 20.8 |
| Currently working | 59 | 29.5 | 27 | 26.0 | 32 | 33.3 |
| Receiving disability income | 90 | 45 | 46 | 44.2 | 44 | 45.8 |
| Individual monthly income | ||||||
| <$500 | 33 | 16.5 | 20 | 20.0 | 13 | 13.7 |
| $500–$1,000 | 66 | 33.8 | 35 | 35.0 | 31 | 32.6 |
| $1,000–$1,499 | 36 | 18.5 | 20 | 20.0 | 16 | 16.8 |
| $1,500–$1,999 | 17 | 8.7 | 6 | 6.0 | 11 | 11.6 |
| $2,000–$2,499 | 18 | 9.2 | 8 | 8.0 | 10 | 10.5 |
| ≥$2,500 | 25 | 12.9 | 11 | 11.0 | 14 | 14.8 |
| Mental health diagnoses (from medical records) | ||||||
| Schizophrenia spectrum disorder | 58 | 29.0 | 31 | 29.8 | 27 | 28.1 |
| Bipolar disorder or affective psychosis | 138 | 69.0 | 71 | 68.2 | 67 | 69.8 |
| Posttraumatic stress disorder | 4 | 2.0 | 2 | 1.9 | 2 | 2.1 |
| Current medications | ||||||
| Blood pressure medications | 59 | 29.5 | 30 | 28.8 | 29 | 30.2 |
| Diabetes medications | 30 | 15.0 | 14 | 13.5 | 16 | 16.7 |
| Cholesterol medications | 49 | 24.5 | 27 | 26.0 | 22 | 22.9 |
| Atypical antipsychotic medications | 182 | 91.0 | 95 | 91.3 | 87 | 90.6 |
| Lithium or anticonvulsant medications | 97 | 48.5 | 51 | 49.0 | 46 | 47.9 |
| Antidepressant medications | 33 | 16.5 | 15 | 14.4 | 18 | 18.8 |
| Current psychiatric medications classified according to weight loss/gain profilea | ||||||
| ≥1 slight/moderate weight loss | 77 | 38.5 | 39 | 37.5 | 38 | 39.6 |
| ≥1 weight neutral | 168 | 84.0 | 87 | 83.7 | 81 | 84.4 |
| ≥1 slight/moderate weight gain | 21 | 10.5 | 10 | 9.6 | 11 | 11.5 |
| ≥1 severe weight gain | 128 | 64.0 | 68 | 65.4 | 60 | 62.5 |
a
For details of medications included in each category, see the online data supplement .
Study Retention and Intervention Attendance
Follow-up data collection was completed for 91% of participants (N=181) at 6 months and for 85% (N=170) at 12 months, with no differential attrition (χ2=0.01, df=2, p=1.00). Missing data were thus unlikely to be conditional on group assignment. The average number of sessions attended during the initial intervention was 14.5 (SD=7.2) out of 24 (60.2%) among intervention participants, and the average number of maintenance sessions attended was 2.7 (SD=2.17) out of six (44.5%).
Analyses
The adjusted time-by-group coefficients and confidence intervals for intent-to-treat analyses are summarized in Table 3.
| Variable | Δ Baseline–6 Months | Δ 6 Months–12 Months | Δ Baseline–12 Months | pb | |||
|---|---|---|---|---|---|---|---|
| Coefficienta | 95% CI | Coefficienta | 95% CI | Coefficienta | 95% CI | ||
| Weight (kg) | –4.37 | –6.96 to –1.78 | 1.77 | –0.87 to 4.40 | –2.60 | –5.14 to –0.07 | 0.004 |
| Body mass index (kg/m2) | –1.55 | –2.47 to –0.63 | 0.58 | –0.35 to 1.50 | –0.97 | –1.88 to –0.06 | 0.004 |
| Systolic blood pressure (mmHg) | –1.60 | –5.21 to 2.02 | 1.68 | –1.91 to 5.27 | 0.09 | –3.36 to 3.53 | 0.60 |
| Diastolic blood pressure (mmHg) | –1.21 | –3.58 to 1.17 | 0.82 | –1.59 to 3.23 | –0.38 | –2.89 to 2.12 | 0.59 |
| Fasting glucose (mg/dL) | –0.02 | –0.08 to 0.05 | –0.08 | –0.14 to –0.01 | –0.09 | –0.16 to –0.02 | 0.02 |
| Fasting insulin (μU/mL) | 0.11 | –0.09 to 0.31 | –0.12 | –0.58 to 0.34 | –0.01 | –0.46 to 0.43 | 0.56 |
| Homeostasis model assessment-insulin resistance indexc | 0.09 | –0.12 to 0.30 | –0.15 | –0.37 to 0.07 | –0.24 | –0.48 to 0.01 | 0.17 |
| Diabetes riskd | 0.17 | –1.55 to 1.89 | –1.56 | –3.39 to 0.26 | –1.39 | –3.09 to 0.31 | 0.17 |
| Fasting triglycerides (mg/dL) | 3.72 | –21.57 to 29.01 | 0.67 | –21.52 to 22.86 | 4.39 | –24.18 to 32.96 | 0.95 |
| Fasting low-density lipoprotein (mg/dL) | –1.65 | –8.52 to 5.22 | 1.68 | –5.25 to 8.61 | 0.03 | –7.58 to 7.64 | 0.85 |
| Fasting high-density lipoprotein (mg/dL) | 1.23 | –0.70 to 3.16 | 1.05 | –1.14 to 3.24 | 2.28 | –0.14 to 1.05 | 0.17 |
a
Values represent the coefficient for the time-by-group indicators estimated from the generalized estimating equation models.
b
An omnibus Wald test was used to assess whether the joint effect of the time-by-group indicators equaled 0.
c
The calculation for the index is as follows: fasting glucose [mmol/L] × fasting insulin [μU/mL]/22.5; lower scores indicate lower risk for developing insulin resistance; coefficients represent the change in the natural log of the index.
d
Data are based on the Framingham Diabetes Risk Scale; lower scores represent decreased risk of developing diabetes.
Primary outcomes.
There was a significant time-by-group effect for weight and BMI. The intervention group lost 4.4 kg more than the control group (95% confidence interval [CI]=–6.96 kg to –1.78 kg) at 6 months and 2.6 kg more than the control group (95% CI=–5.14 kg to –0.07 kg) at 12 months. As expected, there was no significant difference in weight change between the groups (1.77 kg, 95% CI=–0.87 kg to 4.40 kg) during maintenance (6–12 months). Estimated marginal means are presented in Figure 2 and Figure 3; results for BMI parallel weight results.
FIGURE 3. Adjusted Mean Outcomes of Intervention and Control Groups From Baseline to 12 Monthsa
a Abbreviations: LDL=low-density lipoprotein; HDL=high-density lipoprotein; HOMA-IR=homeostasis model assessment-insulin resistance.
Among participants with complete data at baseline and the 6-month follow-up, the intervention group (N=93) lost an average of 3.9% and the control group (N=85) gained an average of 0.9% of their baseline weight (F=11.9, df=1, 171, p=0.001). From baseline to 12 months, the intervention group (N=87) lost a greater percentage of their baseline weight (4.5%) than the control group (N=81, 1.7%) (F=4.9, df=1, 161, p=0.03). There was marginal evidence that the intervention group was more likely to be at or below their baseline weight at 6 months (odds ratio=1.69, 95% CI=0.91 to 3.14, p=0.10) and 12 months (odds ratio=1.88, 95% CI=0.98 to 3.64, p=0.06), compared with the control group. The intervention group had 3.78 times greater odds (95% CI=1.82 to 7.84, p<0.001) of more than 5% loss of baseline weight by 6 months compared with the control group; 40% of intervention participants achieved at least 5% of baseline weight loss compared with 17% of control participants. This effect was not significant at 12 months (odds ratio=1.64, 95% CI=0.87 to 3.08, p=0.13), although nearly one-half (47%) of intervention participants with complete data lost at least 5% of baseline body weight compared with 36% of control participants. At 6 months, the intervention group had 5.14 times greater odds of achieving a ≥10% loss of baseline weight than the control group (95% CI=1.62 to 16.30, p=0.005). At 12 months, the intervention group had 3.08 times greater odds of a ≥10% weight loss (95% CI=1.20 to 7.91, p=0.02). At 6 months, 18% of intervention participants and 5% of control participants had lost at least 10% of their baseline body weight, while 22% of intervention participants and 9% of control participants met this threshold at 12 months. Consistent with findings of weight reduction in both groups, 21.5% of intervention participants reported additional weight-loss activities, compared with weight-loss efforts among 41.7% of control participants (χ2=8.38, df=1, p=0.004).
Distributions for fasting glucose, insulin, and homeostasis model assessment-insulin resistance index were positively skewed, and therefore we fitted log transformations for these outcomes using a Gaussian-based generalized estimating equations model and a generalized estimating equations model using the negative binomial distribution and log link (except for homeostasis model assessment). For fasting glucose and insulin, we report results of the negative binomial generalized estimating equations. There were no significant time-by-group interactions for fasting insulin, Framingham Diabetes Risk Score, or homeostasis model assessment-insulin resistance index. However, there was a significant time-by-group interaction for fasting glucose (p=0.02). From baseline to 12 months, the intervention group showed a greater decline in fasting glucose (log of the incidence rate ratio=−0.089, p=0.01) compared with the control group. Fasting glucose among control participants increased from 106.0 mg/dL at baseline to 109.5 mg/dL at 12 months, whereas in the intervention group levels declined from 106.3 mg/dL at baseline to 100.4 mg/dL at 12 months. The difference in change from 6 months to 12 months was also significant (log of incidence rate ratio=−0.075, p=0.02). Levels in the control group increased from 105.1 mg/dL at 6 months to 109.5 mg/dL at 12 months, whereas levels in the intervention group declined from 103.7 mg/dL at 6 months to 100.4 mg/dL at 12 months. Difference in change from baseline to 6 months was not significant (p=0.64). The proportion of control arm participants who had fasting glucose values <100 at baseline, 6 months, and 12 months was 0.45, 0.46, and 0.42, respectively, and the proportion in the intervention arm was 0.59, 0.60, and 0.68, respectively. While there was no difference in the proportion of participants with glucose values <100 at 6 months (p=0.59), participants in the intervention group had 2.39 (95% CI=1.12 to 5.12) times greater odds of glucose values <100 at 12 months compared with the control group (p=0.04).
Secondary outcomes.
Changes in systolic and diastolic blood pressure from pre- to postintervention were not significant, likely because average values were within normal ranges at baseline. Time-by-group interactions were not significantly different for triglycerides or low- or high-density lipoprotein cholesterol, although average low-density lipoprotein cholesterol was also within normal range at baseline. Correlations between changes in weight at 6 months and food logs kept (r=−0.45, p<0.001), sleep logs kept (r=−0.39, p<0.001), and number of sessions attended (r=−0.43, p<0.001) were significant. The greater the number of food and sleep logs kept and the higher the attendance, the greater the weight loss. No significant correlations were found between logs or attendance and glucose levels.
Acute service use and adverse events.
There were significantly fewer medical hospitalizations in the intervention arm than in the control arm over the 12-month period: 6.7% of intervention participants reported medical hospitalizations compared with 18.8% of control participants (χ2=6.66, df=1, p=0.01). There were no differences in psychiatric hospitalizations: 15.6% of control participants compared with 15.4% of intervention participants had hospitalizations (χ2=0.97, df=1, p=0.32). There were no differences in emergency department visits that did not result in hospitalizations for either medical or psychiatric problems. There was one death in each arm, neither related to study participation.
Discussion
Our results support recent findings (14) suggesting that behavioral lifestyle-change programs can help individuals with serious mental illnesses to lose weight, and extend these findings by showing that lifestyle interventions can produce changes in fasting glucose levels among individuals taking antipsychotic medications—drugs known to disrupt glucose metabolism (7, 31). Consistent with other interventions (16), STRIDE spurred clinically significant weight loss of ≥5% of initial body weight among 40% of participants. Weight loss of ≥10% was achieved by 18%, and participants in the intervention group were 2.39 times as likely as participants in the control group to have normal fasting glucose levels at 12 months. In addition, we observed substantially fewer medical hospitalizations in the intervention group than in the control group. If these results are replicated, reduced hospital costs could be an added benefit of offering these interventions.
Our goal was to produce an average weight loss of 4.5 kg–6.8 kg (10–15 pounds), consistent with the original PREMIER intervention goal for people without serious mental illnesses. STRIDE participants lost an average of 4.2 kg (9.3 pounds, adjusted means). Unadjusted means (for those with full data only) showed losses of 5.8 kg (12.8 pounds) in the intervention group. Participants in the PREMIER intervention, DASH diet arm, lost an average of 4.7 kg more than those in the control group, while STRIDE intervention participants lost 4.4 kg more than those in the control group. The similarity of the STRIDE and PREMIER outcomes is remarkable given known barriers to weight loss among individuals with serious mental illnesses. Moreover, STRIDE participants were heavier than PREMIER participants at baseline, with BMIs of 38.3 and 33.6, respectively. Thus, individuals in STRIDE needed to lose many more pounds to achieve a “clinically significant” 5% loss compared with PREMIER participants. Participants in the control group also lost weight, although much less than participants in the intervention group. This likely stems from referrals to primary care following study assessments for at-risk values and because individuals who joined the trial were motivated to lose weight and attempted to do so after assignment to the control group, including using other formal weight-loss methods and programs.
Our results parallel the ACHIEVE (Randomized Trial of Achieving Healthy Lifestyles in Psychiatric Rehabilitation) (32) trial results and are consistent with those of other randomized controlled trials in showing positive results of weight-loss interventions in this population (16). However, other than the ACHIEVE trial, randomized controlled trials assessing similar lifestyle interventions in similar populations have been of short duration (e.g., 12–16 weeks), and thus are not directly comparable. The In SHAPE program (33) was similar in target population and in length and intensity, but the intervention was focused on exercise (12 months of weekly meetings with a fitness trainer and fitness club membership). In SHAPE was associated with a clinically significant reduction in cardiovascular risk in 49% of participants and produced improvements in fitness and diet, but not in weight, when compared with an active control consisting of a health club membership and fitness education. In another study of similar length and intensity, Wu et al. (34) implemented a 6-month diet and exercise program for obese adults with schizophrenia taking clozapine and reported a 6-month weight loss quite similar (−4.2 kg) to what we found in STRIDE but under highly controlled inpatient circumstances.
Thus, the most useful comparisons for STRIDE results are with the ACHIEVE trial, which implemented a similar lifestyle intervention in an outpatient population. A notable difference, however, was that the setting for ACHIEVE was within psychiatric rehabilitation programs that participants attended for several hours daily. The intervention capitalized on the setting by including group weight-management and exercise sessions, as well as individual sessions, as part of daily programming. Additionally, programs routinely provided two meals per day for participants, and researchers worked with staff to include more healthy offerings. ACHIEVE participants lost weight steadily over 18 months, with an average loss of 3.4 kg. In contrast, STRIDE participants traveled to stand-alone groups weekly, achieved a 4.4-kg loss over 6 months, but gained some of this weight back during the maintenance phase. Process evaluation data suggested that STRIDE participants who were engaged in the intervention wanted the weekly contact to continue, and the relationship between keeping food and sleep logs and greater weight loss indicates that increasing the length of the more intensive intervention could be beneficial. ACHIEVE results support this contention, showing that sustained support can result in continued lifestyle improvements. This may indicate that providing access to STRIDE for longer periods could result in substantial additional improvements in weight and cardiometabolic outcomes. Observed reductions in fasting glucose, and trends toward improvements in several other outcomes (fasting insulin, homeostasis model assessment-insulin resistance index, Framingham Diabetes Risk Score, high-density lipoprotein cholesterol), are consistent with this conclusion. Moreover, STRIDE study participants had average baseline fasting glucose levels of 109 mg/dl (35) and were therefore similar to participants enrolled in diabetes prevention trials with multiyear lifestyle interventions (36, 37). Long-term follow-up in these trials has shown sustained diabetes risk reduction (35, 38, 39).
Patient Perspectives
Interviewed Participants Reported that Helpful Features Included Camaraderie and Support Resulting from Shared Mental Health Experiences and Health-Related Goals:
“I really enjoyed the group setting. And I could sit next to anybody in the class and be perfectly comfortable. Because we all shared this kind of common mental health issue … I really liked the support …. You know, how did you do this week? What were your successes? What were your failures? The part I didn’t like was when the group setting ended. That was hard for me. I tried to go out and find another group … like Weight Watchers, and I couldn’t find a group that I clicked with. So it was really frustrating to have that camaraderie and then lose it.”
Also Appreciated was Support of Self-Determination to Make Broad Lifestyle Changes:
“I thought it was wonderful because it didn’t box you in that you had to do anything rigid. It stressed lifestyle changes …. I felt no immediate pressure that I had to lose 40 pounds or 50 pounds in a year…. The offering was there: We’re here to help you. And so what I decided to do made the difference, so I got committed because I decided to do it.”
Some Aspects of Participation were Easier than Others:
“One thing that was also hard … being weighed weekly and being reminded weekly that … you go 2, 3, 4 weeks where there’s no change, or you might have went up …. That’s really hard.”
“The thing that just bothers me right now is … the daily journal. It’s gotten to be a bit of a grind after a while … but I can see where I’m going with what I’ve been eating, counting up the calories. [Is that helpful to you?] Yeah; real helpful.”
Limitations and Opportunities
Our results and the study’s limitations suggest opportunities for improving intervention and outcomes. First, attendance during the initial intervention was lower than desired (about 60%). Although this is similar to ACHIEVE attendance (32), and not unexpected given instability in the lives of people with serious mental illnesses, it represents a study limitation, an implementation challenge, and an opportunity to improve outcomes (17), particularly given the relationship we found between greater attendance and weight loss. Reach of the intervention was also a limitation: 1) the average age of participants was approximately 47 years, and thus health-related risks were well established; and 2) only 28% of participants were men and only 14% were members of racial or ethnic minority groups, despite efforts to recruit equal numbers of men and women and to oversample minority group members. Although this pattern is typical of lifestyle-change programs (25, 33, 40, 41), it nevertheless suggests that special efforts are needed to make interventions more appealing to these groups. In terms of design limitations, although this was a randomized controlled trial (with the advantage of achieving balance on unmeasured covariates compared with other research designs), we neither measured nor controlled for medical severity or comorbidity because these data were not available from participating community mental health centers and beyond our capacity to measure at study assessments.
Conclusions
Individuals taking antipsychotic medications can lose significant amounts of weight and improve fasting glucose levels in a tailored, comprehensive weight-loss and lifestyle-change program. Increasing the length of the intervention and the number of sessions attended holds potential to support additional weight loss and glucose control and to address other cardiometabolic risk factors. Increasing the reach of the intervention is an important step in advancing research on health interventions for people with serious mental illnesses.
Acknowledgments
The authors thank the scientific collaborators and the clinical and project management staff that supported this trial, as well as the STRIDE participants.
Footnote
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Information & Authors
Information
Published In
History
Received: 10 February 2014
Revision received: 2 April 2014
Revision received: 14 May 2014
Accepted: 23 June 2014
Published ahead of print: 31 October 2014
Published online: 1 January 2015
Published in print: January 01, 2015
Authors
Competing Interests
Dr. Green has received grant support from AHRQ, the Kaiser Permanente Center for Safety and Effectiveness Research, the Kaiser Permanente Community Benefit Initiative, NIDA, NIDDK, NIH, NIMH, and Purdue Pharma; she has also provided research consultation for The Industry PMR (the Industry PMR consortium is comprised of Actavis, Endo Pharmaceuticals, Janssen Pharmaceuticals, Mallinckrodt, Pfizer, Purdue Pharma, Rhodes Pharmaceuticals, Roxane Laboratories, and Zogenix). Dr. Yarborough has received grant support from AHRQ, the Kaiser Permanente Center for Safety and Effectiveness Research, the Kaiser Permanente Community Benefit Initiative, NCCAM, NIDA, NIDDK, NIMH, and Purdue Pharma. Dr. Leo has received funding from GenomeDX Biosciences and Pfizer. Mr. Yarborough has received grant support from the Kaiser Permanente Community Benefit Initiative, NIDDK, NIMH, and Purdue Pharma. Mr. Stumbo has received grant support from AHRQ, the Health Resources and Services Administration, the Kaiser Permanente Community Benefit Initiative, the Lucile Packard Foundation for Children’s Health, Maternal and Child Health Bureau, NCCAM, NIDDK, NIMH, and Purdue Pharma. Ms. Janoff has received grant support from AHRQ, the Kaiser Permanente Center for Safety and Effectiveness Research, NIDA, NIDDK, NIMH, and Purdue Pharma. Dr. Perrin has received grant support from AHRQ, the Centers for Disease Control and Prevention, the Kaiser Permanente Community Benefit Initiative, Kaiser Permanente Northwest, Merck, NCCAM, NCI, NCMHD, NHLBI, NIA, NICHD, NIDA, NIDDK, NIMH, NINR, NIOSH, Purdue Pharma, and the Veterans Administration. Dr. Nichols has received grant support from AHRQ, AstraZeneca, Bristol-Myers Squibb, GlaxoSmithKline, NHLBI, NIDDK, NIH, Novartis Pharmaceuticals, and Merck. Dr. Stevens has received grant support from AHRQ, NCCAM, NCI, NCRR, NHLBI, NICHD, NIDDK, NIH, and Kaiser Permanente Northwest.
Funding Information
National Institute of Diabetes and Digestive and Kidney Diseases10.13039/100000062: R18DK076775
Supported by the National Institute of Diabetes and Digestive and Kidney Diseases, grant R18DK076775.Metrics & Citations
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