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Research Article                                                                                                                                        Open Access

## Behavioral Weight Loss Treatment for Youth Treated With Antipsychotic Medications

Ginger E. Nicol 1* , Rachel P Kolko 2 , Monica Mills 1 , Thrudur Gunnarsdottir 3 , Michael D. Yingling 1 , Julia A. Schweiger 1 , Eric J. Lenze 1 , John W. Newcomer 4 , Denise Wilfley 5-8

1 Healthy Mind Lab, Dep. of Psychiatry, Washington University School of Medicine, St. Louis, MO, USA 2 Dep. of Psychiatry, Western Psychiatric Institute, University of Pittsburgh Medical Center, Pittsburgh, PA, USA 3 Dep. of Psychology, University of Akureyri, Iceland

4 Charles E. Schmidt College of Medicine, Florida Atlantic University, Boca Raton, FL, USA 5 Weight management & Eating Disorders Program, Dep. of Psychiatry, Washington University School of Medicine, St. Louis, MO, USA 6 Dep. of Psychology, Washington University School of Medicine, St. Louis, MO, USA 7 Dep. of Internal Medicine, Washington University School of Medicine, St. Louis, MO, USA 8 Dep. of Pediatrics, Washington University School of Medicine, St. Louis, MO, USA

*Corresponding author: nicolg@psychiatry.wustl.edu

## Abstract

Background: Youth who are being treated with antipsychotic medications are at increased risk for the development of obesity and type 2 diabetes. Behavioral weight loss treatments show promise for reducing obesity and diabetes risk among adults treated with these drugs, but such treatments have not previously been studied in youth.

Objective: We  describe  a  rationale  for  behavioral  weight  loss  intervention  for  high-weight  youth  being  treated  with antipsychotic  medications.  We  report  behavioral,  anthropomorphic,  and  metabolic  findings  from  a  case  series  of  obese adolescents  taking  antipsychotic  medications  who  participated  in  a  short-term,  family-based  behavioral  weight  loss intervention.

Methods: We adapted the Traffic Light Plan, a 16-week family-based weight loss intervention that promotes healthy energy balance using the colors of the traffic light to categorize the nutritional value of foods and the intensity of physical activity. We  then  added  a  social  and  ecological  framework  to  address  health  behavior  change  in  multiple  social  contexts.  The intervention was administered to three obese adolescents with long-term antipsychotic medication exposure. The efficacy of the intervention was evaluated with a battery of anthropomorphic and metabolic assessments, including weight, body mass index percentile, whole body adiposity, liver fat content, and fasting plasma glucose and lipid levels. Participants and their parents also filled out a treatment satisfaction questionnaire after study completion.

Results: Two boys and one girl, all of whom were 14 years old, participated in this study. All three participants attended all 16  sessions  of  the  intervention  and  experienced  beneficial  changes  in  adiposity,  fasting  lipid  levels,  and  liver  fat  content associated with weight stabilization or weight loss. Adolescents and their parents all reported a high level of satisfaction with the treatment.

Conclusions: Family-based  behavioral  weight  loss  treatment  can  be  feasibly  delivered  and  is  acceptable  to  youth  taking antipsychotic medications and their families. Randomized controlled trials are needed to fully evaluate the effectiveness and acceptability of these treatments for these individuals.

ClinicalTrials.gov Identifier: NCT01222494

Keywords: pediatric obesity; antipsychotics; at-risk youth; weight loss treatment

## Introduction

Pediatric obesity is a rising public health concern that is  associated  with  the  early  onset  of  cardiovascular disease risk conditions such as fatty liver and diabetes (1-3).  Children  with  psychiatric  conditions  may  be particularly vulnerable to the development of obesity and related adverse health conditions (4).  The increased risk for obesity in psychiatric populations is  exacerbated  by  the  use  of  second-generation antipsychotic  medications  (hereafter  referred  to  as antipsychotics ), which increase the risk for weight gain and  related  adverse  changes  in  lipid  and  glucose metabolism (5,6). Youth who are being treated with antipsychotics  are  more  than  twice  as  likely  as children in the general population to develop obesityrelated cardiometabolic risk conditions like diabetes, hypertension, and hyperlipidemia (7-9). For populations in which obesity is the result of medical treatments, first-line treatment strategies include the discontinuation of agents that cause or contribute to weight gain and substitution with a lower-risk agent if one is available (10; p. 2489 ). Although antipsychotic discontinuation in youth is associated with  weight  loss,  it  may  come  at  the  price  of psychiatric symptom recurrence, including aggressive or  self-injurious  behavior  (11-13).  Therefore,  it  is imperative  to  identify  strategies  to  mitigate  weight gain when maintenance treatment with antipsychotics is necessary.

The putative mechanisms of antipsychotic-induced weight gain are related to the medications' combination of dopamine blockade at D2 receptors, antagonism or inverse agonism at 5HT2C serotonin receptors, antagonism at 5HT2A serotonin receptors, antagonism  at  alpha-1A  adrenergic  receptors,  and especially antagonism at histamine-1 receptors (14). Blocking  the  activity  of  dopamine-particularly  in the  subcortical,  limbic,  and  striatal  areas  of  the brain-leads  to  an  upregulation of postsynaptic receptors as well as increased dopamine within the synaptic cleft, which may create a 'reward deficiency' syndrome  that  prevents  satiety (15). Serotonin  receptor  inverse  agonism  or  antagonism may  lead to decreased satiety and hyperphagia (16,17). Finally, weight gain has long been associated with centrally active drugs that have high affinity for the  histamine-1  receptor,  and  H1  antagonism  is known to increase feeding (18,19) and sedation, with predictable  reductions  in  caloric  expenditure  (14). Although treatment-related weight gain is pharmacologically  driven,  it  could  potentially  be addressed by behavioral strategies that affect decreased satiety, increased food seeking, and sedentary  behavior.  Core  principles  of  behavioral weight loss that may impact satiety and activity level typically involve food and activity substitutions, with progressive goal setting and reinforcement to reach the identified terminal health behavior targets and to change food and activity preferences.

Intensive behavioral weight loss and lifestyle modification programs have been successfully adapted for use in adults with psychotic disorders and other severe mental illnesses who are taking antipsychotics  (20-22).  One  particularly  successful weight loss intervention has incorporated psychosocial  and  cognitive  rehabilitation  strategies into  a  health  education  framework  in  a  setting  in which patients received mental health care and social support (23)). Social ecological approaches to health behavior change in psychiatric populations consider the adjustment, coping, and adaptive functioning of the  individual  within  a  social  and  cultural  context (24). This focus on facilitating the individual's involvement in and impact on the environment as an agent of change is thought to enhance the likelihood of  the  sustained  improvement  of  health  behaviors. Social ecological models of pediatric health behavior change include the family as an integral part of the child's  immediate  environment  and  promote  the development  of  parent-facilitated  social  networks that support health behavior change and that address social barriers to engaging in health behavior change (25,26).  Weight  loss  treatments  that  make  use  of  a social ecological approach to health behavior change may be ideally suited to promoting health behavior change  in  mentally  ill  youth,  because  psychosocial barriers to participation may be more pronounced as compared with populations of non-psychiatrically ill individuals.  Family  is  part  of  the  first  and  perhaps most important layer of social ecology in the lives of children, and thus social ecological approaches that focus on the involvement of social supports, including family, may be of primary importance for individuals who face psychiatric illnesses as barriers to health behavior change.

Family-based behavioral weight loss treatment (FBT)  is  considered  a  first-line  treatment  for  the management of pediatric obesity (27,28). Published meta-analyses have documented that such interventions  lead  to  improved  weight  outcomes among  children  and  adolescents  (29,30).  However, these reports also highlight the need for studies that evaluate treatment-related changes in metabolic parameters and that test strategies for enhancing realworld  intervention  delivery,  particularly  in  at-risk populations  such as individuals with psychiatric illnesses who are treated with antipsychotics (31). To our knowledge, two studies that included behavioral weight  loss  as  part  of  the  study  design  have  been conducted in overweight or obese youth treated with antipsychotics (32,33). However, we are aware of no published studies evaluating the feasibility and efficacy of family-based behavioral weight loss interventions  in  this  population  nor  of  any  studies that  measure  the  impact  of  such  interventions  on metabolic health outcomes.

The  present  report  describes  a  modified  FBT approach to weight loss among youth taking antipsychotics and reports on the first three participants in a randomized  controlled  trial to evaluate the efficacy of FBT for weight loss in youth between  the  ages  of  6  and  18  years  treated  with antipsychotics.  The  design  of  this  study  involves delivering  weekly  FBT  to  youth  with  psychiatric illnesses  treated  with  antipsychotics  as  compared with  otherwise  healthy  but  overweight  or  obese youth,  with  a  monthly  standard-of-care  reference group treated with antipsychotics.  The primary outcomes of this study include gold-standard measures  of  body  composition  and  metabolism: changes in total percentage of body fat and liver fat, measured respectively via dual energy X-ray absorptiometry and magnetic resonance spectroscopy;  common  clinical  measures,  such  as body  mass  index  (BMI)  and  BMI  percentile;  vital signs; and fasting plasma lipid and glucose values. We hypothesize that individuals treated with antipsychotic  agents  can  successfully  participate  in behavioral  weight  loss  treatment  without  adverse weight or metabolic outcomes. Here, we describe the weekly FBT program adapted for use in youth treated with antipsychotics to incorporate a social ecological approach, and we report changes in weight and other measures  of  metabolic  health  in  the  initial  three patients who completed the weight loss treatment.

## Participants

Three  adolescent  participants  were  recruited  from the Washington University School of Medicine Child and Adolescent Psychiatry Outpatient Clinic. In all cases,  the  participant's  pediatrician  or  primary  care provider  was  notified  of  study  participation  and provided  medical  assent.  Outpatient  weights  and heights  collected  during  the  year  prior  to  study enrollment  were  obtained  for  all  participants  from their  primary  care  provider  or  treating  psychiatrist. Inclusion criteria for the overall study included the following:

- 1) overweight  (BMI  percentile  ≥85)  or  obese (BMI percentile ≥95) youth between the ages of 6 and 18 years;
- 2) any Diagnostic  and  Statistical  Manual  of  Mental Disorders, Fourth Edition, Text Revision diagnosis;
- 3) at  least  6  continuous  months  of  treatment with antipsychotics;
- 4) documented weight gain that was greater than expected (e.g., crossing a percentile line on the BMI growth chart);
- 5) evidence of psychiatric stability (i.e., no inpatient hospitalizations during the previous 6  months  and  no  changes  in  psychotropic medication doses for 4 weeks);
- 6) consenting adult caregiver willing to participate in the study; and
- 7) ability  to  provide  assent  for  participation  as evidenced by documented or clinically estimated intelligence quotient of 70 or higher.

Exclusion criteria included the following:

- 1) youth who were not overweight or obese by BMI percentile;
- 2) age outside the specified range of 6 to 18 years;
- 3) no  presence  of  any Diagnostic  and  Statistical Manual of Mental Disorders, Fourth Edition, Text Revision diagnosis;
- 4) less than 6 months of antipsychotic treatment;
- 5) active suicidality or substance use disorders;
- 6) lack of psychiatrically stability and/or antipsychotic treatment deemed inappropriate;
- 7) no consenting adult caregiver able to participate in the study; and
- 8) estimated or documented intelligence quotient of less than 70.

Concurrent treatment with selective serotonin reuptake inhibitors and attention-deficit/ hyperactivity disorder medications (including stimulants,  Atomoxetine,  or  alpha-agonist  agents below a total daily dose of 2 mg/kg methylphenidate equivalent) was permitted to increase the generalizability  of results.  A  large  portion  of  youth treated with antipsychotics are concurrently treated with selective serotonin reuptake inhibitors, stimulants, and other psychotropic medications (34). More  specifically, the use of antipsychotics  for treatment-resistant attention-deficit/hyperactivity disorder is increasingly common (35).

## Study Assessments

Participants were youth between the ages of 6 and18 years who were enrolled in the National Institute of Mental  Health-funded  'Measurement  of  Cardiometabolic  Risk  in  Antipsychotic  Treated  Youth' study. This  is a  randomized  controlled  trial  to evaluate metabolic changes in overweight or obese youth treated with antipsychotics during behavioral weight  loss  treatment  as  compared  with  obese  or overweight but otherwise healthy controls undergoing the same behavioral weight loss treatment. All participants underwent a clinical evaluation by a study psychiatrist to ensure psychiatric stability and the appropriateness of continued antipsychotic treatment during study participation. Diagnoses were based on Diagnostic and Statistical  Manual  of  Mental  Disorders,  Fourth  Edition, Text Revision criteria  and  corroborated with records of previous psychiatric treatment. A consensus study diagnosis was based on the preponderance of clinical and study data. Baseline assessments were conducted within one month of study enrollment, and endpoint assessments  were  conducted  within  two  weeks  of completing  the  16-week  weight  loss  treatment.  All blood  draws  and  physical  study  assessments  were performed  at  the  Washington  University  Pediatric Research Unit; imaging was performed at the Center for Clinical Imaging in Research and at the Nutrition Obesity Research Center and included the following: height  and  weight  measurements  performed  on  a calibrated stadiometer (Seca 240 Wall-Mounted Stadiometer, Germany) and scale (Seca 684 Digital Multifunctional  Scale,  Germany),  respectively,  by  a trained  research  nurse  whole  body  fat  percentage measured  using  dual  energy  X-ray  absorptiometry (Delphi W densitometer equipped with version 12.4 software; Hologic, Waltham, MA); intrahepatic triglyceride content determined at baseline and at the study endpoint by proton magnetic resonance spectroscopy  with  a  1.5  T  scanner  (Magnetom Sonata; Seimens, Erlangen, Germany), with all frequencies (i.e., chemical shifts) measured relative to the principal water  1 H resonance; and fasting plasma lipid  (i.e.,  total  cholesterol,  low  density  lipoprotein cholesterol, high density lipoprotein cholesterol, and triglyceride)  and  glucose  levels.  Weekly  treatment weights were measured on a digital office-based scale (Health  o  meter,  Sunbeam  Products  Inc.,  Boca Raton, FL). BMI, BMI percentile, and BMI Z-score were  calculated from  medical  records for each subject at 12 and 6 months prior to study enrollment and at the baseline and endpoint study assessments. The Washington University in St. Louis Institutional Review Board approved this study.

## Treatment Description

FBT is an evidence-based intervention that consists of  weekly  sessions  for  12  to  24  weeks  and  that includes individual family member weigh-ins, meetings with a trained interventionist, and separate parent  and  child  groups  (36).  FBT  targets  family support and restructuring of the home environment to enable healthier behaviors while establishing selfregulatory  behaviors  to  promote  weight  management. A weight loss goal range of 0.5 to 2 lb per week is set for both participating children and adults; this range is in line with evidence-based  childhood obesity  treatment  (37)  and  recommenddations  for healthy child development and weight management /27,38). Expected annual weight gain during normal growth and development varies on the basis of age and gender and can range from 2 to 3 lb per year in prepubertal and postpubertal youth to 8 to 12 lb per year  during  the  prepubertal  and  pubertal  growth stages, with weight gain being higher in prepubertal females  as  compared  with  males  and  higher  in pubertal males as compared with females (39,40). For individuals  who  are  already  at  a  high  weight,  the range of 0.5 to 2 lb per week is a safe weight loss range  for all  ages  and  stages  of  growth.  Core components  of  behavioral  weight  loss  strategies include  education  about  energy  balance,  shaping behaviors  to  promote  stimulus  control,  and  selfmonitoring.  The  Traffic  Light  Plan  is  used  as  a framework to help families shift their energy intake and  expenditure  with  the  use  of  a  classification system in which the nutritional values of foods and the intensity values of activities are coded as RED for 'stop and think' to indicate the least healthy options, YELLOW  for  'caution'  to  indicate  moderately healthy  options,  and  GREEN for 'go' to indicate the  healthiest  options  (41-44).  Both  participating parents  and  youths  are  asked  to  self-monitor  their daily  food  intake  and  physical  activity.  Youth  and their participating parents are asked to select from a list  of  behavioral  rewards  (which  exclude  options related to food or sedentary behavior) for accumulating  points  when  weekly  goals  are  met. Child and parent weights are measured during each in-person session.

In the present case series, modifications were made to the existing FBT framework to facilitate delivery in an outpatient psychiatric treatment setting. First, we removed the weekly group meeting and increased contact with the treatment team through a mid-week phone  check-in,  and  we  incorporated  the  group content and skills practice into the individual family sessions. This was done to reduce the total time spent in person per week by families and interventionists and to allow interventionists to provide support and reminders  to  engage  in  self-monitoring  and  health behavior  changes  throughout  the  week.  We  also employed a simplified, one-page food and activity log composed  of  visual  cues  for  RED  and  GREEN foods and activities. This was done to simplify food logging  for  youth  who  had  learning  disabilities  or other  cognitive  challenges.  We  created  and  used  a 'taste  log'  to  incentivize  trying  new  GREEN  and YELLOW foods and to promote serial desensitization  for  youth  with  food  aversions  or selective eating patterns. In addition, we included an ecological-based social facilitation  component  in each session to encourage the consolidation of health behavior changes across environmental contexts; we took  into  account  the  developmental  stage  of  the participating  youth,  and  we  encouraged  parents  to facilitate  the  development  and  use  of  peer  and community  networks  to  support  health  behavior change.  Weekly  treatment  goals  were  divided  into energy  balance,  weight  loss,  and  social  facilitation domains, and target ranges for scaled goal attainment were created within each domain. This allowed the interventionist to individualize weekly goals on the basis  of  child-  and  family-level  characteristics  and needs.

## Results

Table  1  presents  each  of  the  three  cases  in  detail. Common characteristics among participants included age, race, and weight related medical comorbidities  (e.g.,  dyslipidemia,  impaired  fasting glucose).  Additionally,  each  case  presented  unique parenting  challenges  related  to  either  parental  or child psychiatric considerations. Quantitative cardiometabolic outcomes are presented in Table 2. Beneficial  changes  in  fasting  total  cholesterol,  low density  lipoprotein  cholesterol,  adiposity,  and  liver fat content were documented for Participant 1 and Participant 3, who both experienced greater changes in  BMI  percentile  and  Z-score  as  compared  with Participant 2. All participants experienced a slowing of weight gain as compared with their pretreatment weight trajectories (Figure 1). No clinically significant changes  in  fasting  glucose  and  triglyceride  values were found. Participating parents and youth reported that  they  were  either  'very  satisfied'  (n  =  2)  or 'somewhat  satisfied'  (n  =  1)  with  the  treatment program at study completion. Two parents reported that  they  would  not  suggest  any  changes  to  the treatment; one parent suggested the use of a computer or mobile device application for homework and self-monitoring.

## Conclusions

Children with mental health conditions-especially those who  are treated with antipsychotics-are vulnerable to developing obesity and related health problems. Little research has been conducted regarding weight loss interventions in this population. FBT interventions are low risk and are considered first-line treatments for pediatric obesity, with evidence for long-term sustainability (36). The preliminary  results  reported  here  represent,  to  our knowledge, the first reported for a behavioral weight loss  intervention  adapted  for  use  in  youth  treated with antipsychotics.

The  primary  goal  of  this  pilot  study  was  to demonstrate the feasibility of delivering a behavioral weight  loss  treatment  to  families  of  youth  with psychiatric conditions. All participants experienced a beneficial  change  in  or  stabilization  of  their  BMI percentile and Z-score as compared with pretreatment conditions, and these changes are similar to those of previous  FBT  studies  (25). Although  greater  weight  loss  was  associated  with greater changes in metabolic parameters, it is notable that small reductions in weight were associated with measurable  improvements  in  portions  of  the  lipid panel  and  in  liver  fat  content.  Finally,  each  of  the three  cases  involved  a  parenting  component  that challenged the family's ability to maintain a healthy weight, which suggests that a family-based approach may be useful in this population to support parents who want to help their children make health behavior changes (Table 1).

There are important limitations to note. As a case series, the sample of participants reported here was small and warrants continued evaluation, because the results  may  not  be  representative  of  the  general population  of  children  with  psychiatric  conditions who  are  overweight  or  obese.  Moreover,  these participants  were  adolescents,  and  our  larger  trial addresses both children and adolescents between the ages of 6 to 18 years. Estimates of children's height growth patterns can be used to anticipate the weightfor-height changes needed to achieve normal weight status and to guide weight loss targets on the basis of a  youth's  age-  and  sex-specific  BMI  percentiles (45,46).  It  is  important  to  note  that  our  presented cases  are  adolescents  with  BMIs  above  the  99 th percentile for age and gender at entry; children who are  younger  and  closer  to  the  85 th   BMI  percentile need  to  lose  less  weight  to  normalize  their  BMI percentiles  as  compared  with  youth  who  are  older and who have a higher degree of obesity (46). Thus, the  expansion  of  our  sample  to  younger  children across BMI percentiles in the overweight and obese ranges  may  provide  additional  information  about treatment response and may indicate whether treatment  for  this  population,  which  is  at  risk  for continued weight gain, warrants additional adaptation (e.g., whether weight maintenance is more appropriate than weight loss for certain populations)(27,38,46).  In  addition,  there  may  be important differences in an individual's response to these  interventions  as  a  result  of  gender,  ethnicity, age,  and  sociodemographic  variables  that  are  not represented by the individuals discussed in this case series.

Selection  bias  can  confound  results  in  studies  of behavior change: individuals who  participate in research studies may be more motivated than those in  the  general  population  to  make  health  behavior changes. Participant 1 is an example of this and may be  quite  representative  of  individuals  with  mild autism who  also have symptoms  of  attentiondeficit/hyperactivity  disorder;  these  individuals  are commonly treated with a combination of stimulant and  antipsychotic  therapy.  Although  it  could  be argued that Participant 1 lost weight before starting the FBT as a result of concurrent stimulant therapy, which has a known anorectic effect, stimulants have not  been  associated  with  significant  weight  loss among individuals taking antipsychotics (47,48).

## TABLE 1. Participant Characteristics and Case Description

Participant 1 was a 14-year-old Caucasian male diagnosed with PDD-NOS 1  and ADHD, 2  combined type, and Learning Disorder (Reading and Written Expression). He had received psychiatric treatment since age 5, and at study enrollment was taking atomoxetine (Strattera) 100 mg daily, paroxetine (Paxil) 10 mg daily and risperidone (Risperdal) 3 mg daily. Medical comorbidities related to obesity included impaired fasting glucose. 4 Prior to study participation, food limits being set in the home resulted in aggressive behavioral outbursts. Treatment was tailored as follows:

-  To address parent modeling of responsive and assertive communication skills, the therapist worked with parents on how to identify and anticipate behavioral triggers prior to setting limits and boundaries.
-  To address difficulties with recording foods related to learning disorder, daily family check-ins allowed the participant to narrate or dictate food intake to the participating parent, while the youth utilized Traffic Light Plan materials to identify nutrition data for each food item.

Participant 2 was a 14-year-old Caucasian female diagnosed with Mood Disorder Not Otherwise Specified and GAD. 3  She had received psychiatric treatment since age 7, and at study enrollment was taking quetiapine (Seroquel) 100 mg twice daily and 200 mg at bedtime; sertraline (Zoloft) 150 mg daily. Medical comorbidity related to obesity included hypercholesterolemia. 5 Parental health problems, including limited mobility and mild cognitive impairment impacted the ability to perform key parenting skills (e.g., regular grocery shopping, help with completing self-monitoring logs, facilitation of conversations to promote healthy behaviors at home and with peers). Treatment was tailored as follows:

-  To reduce cognitive load, handouts incorporating visual cues and simplified messages regarding the primary message in each meeting were utilized to reinforce session content, and the one-page food and activity log was introduced to simplify self-monitoring.
-  To address parental difficulties and communication challenges, the therapists modeled adaptive communication strategies and provided cues for collaborative problem solving.

Participant 3 was a 14-year-old Caucasian male diagnosed with PDD-NOS 1  and ADHD, 2  combined type. He had received psychiatric treatment since age 3, and at study enrollment was taking osmotic-release oral system (OROS)-methylphenidate (Concerta) 54 mg daily, quetiapine (Seroquel) 150 mg twice daily and 100 mg at bedtime and paroxetine (Paxil) 15 mg daily. Medical comorbidity related to obesity included dyslipidemia. 5 This youth began treatment with a significant preference for RED foods, and taste aversion to most GREEN foods. Parents reported weight had gradually become a problem over time because their child had limited taste preferences and became severely agitated when new foods were introduced. Treatment was tailored as follows:

-  To address distress about trying new foods related to sensory aversion, the interventionist worked with the family on communication strategies and provided support and education about distress tolerance for parents and youth.
-  To engage the youth both during the session and during the week at home and school, a focus of therapy became rewarding attempts to try new GREEN foods using the taste log.

1  Pervasive Developmental Disorder Not Otherwise Specified

2  Attention Deficit-Hyperactivity Disorder

3  Generalized Anxiety Disorder

4  Defined by American Diabetes Association Criteria (33)

5  Defined by NCEP Expert Panel on Blood Cholesterol Levels in Children and Adolescents (34)

TABLE 2. Changes in Metabolic Health During Study Participation

|                                   | Participant 1   | Participant 1   | Participant 2   | Participant 2   | Participant 3   | Participant 3   | Mean           |
|-----------------------------------|-----------------|-----------------|-----------------|-----------------|-----------------|-----------------|----------------|
|                                   | Baseline        | Endpoint        | Baseline        | Endpoint        | Baseline        | Endpoint        | Change (SD)    |
| Weight (lbs)                      | 165.6           | 153.7           | 270.1           | 268.7           | 141.8           | 141.5           | -4.53 (6.40)   |
| BMI %ile                          | 91.13           | 80.94           | 99.48           | 99.41           | 96.16           | 92.69           | -4.58 (5.15)   |
| BMI z-score                       | 1.35            | 0.88            | 2.56            | 2.52            | 1.77            | 1.45            | -0.28 (0.22)   |
| Fasting Glucose (mg/dL)           | 103             | 93              | 87              | 86              | 97              | 97              | -3.67 (5.51)   |
| Fasting Total Cholesterol (mg/dL) | 166             | 145             | 209             | 239             | 160             | 139             | -4.00 (29.44)  |
| Fasting HDL Cholesterol (mg/dL)   | 57              | 62              | 56              | 60              | 41              | 38              | 2 (4.36)       |
| Fasting Triglycerides (mg/dL)     | 59              | 63              | 93              | 106             | 128             | 70              | -13.67 (38.66) |
| Fasting LDL Cholesterol (mg/dL)   | 97              | 70              | 134             | 158             | 93              | 87              | -3 (25.63)     |
| DEXA Total Percent Fat            | 28.4            | 24.2            | 46.9            | 48.4            | 35.6            | 28.6            | -3.23 (4.33)   |
| Percent Liver Fat                 | 2.08            | 0.62            | 1.92            | 2.76            | 3.54            | 1.31            | -0.95 (1.60)   |

300

250-

Weight (Ibs)

150

1004

· Participant 1

· Participant 2

· Participant 3

1-Yr Prior to Treatment

-6 Months

Pre-Treatment Monthly Treatment Session Weights

FIGURE 1. Participant Weight Trajectories, 1 year Pre-Treatment and During Treatment

1 Мого

2 Months

3 Months

During Treatment

<!-- image -->

A more likely cause of weight loss before beginning treatment  is  the  motivation  for  behavioral  change. After  observing  the  pretreatment  weight  trajectory for Participant 1, we modified our study timeline to allow  only  2  weeks  between  baseline  testing  and starting FBT. Finally, although the potential mechanisms of antipsychotic-related weight gain can be  surmised  from  receptor  binding  profiles,  future studies should evaluate the neurobiological changes associated  with  antipsychotic  treatment  and  weight loss treatment to develop more effective and individualized weight loss interventions.

## Clinical Significance

Our findings demonstrates that a minimally modified FBT intervention can be feasibly delivered to youth with psychiatric disorders and could be disseminated via clinical settings in which weekly encounters with behavioral health providers can occur (e.g., community mental health centers). Although beneficial changes were noted in liver fat, whole body adiposity,  fasting  total  cholesterol,  and  low  density lipoprotein cholesterol levels, definitive conclusions regarding the effectiveness of this intervention cannot be made on the basis of the results of these first  three  participants.  Further  study  is  needed  to more definitively determine treatment effectiveness, to clearly identify population- and diagnosis-specific challenges to weight loss, and to determine the most effective  strategies  for  personalizing  treatment  and mobilizing family  member  support  to  promote weight loss success.

## Acknowledgements

This  work  was  made  possible  by  grant  no.  MH  092435 from  the  National  Institutes  of  Mental  Health  and  the Sidney R. Baer, Jr. Foundation. It was also supported by grant  no.  P30DK056341 from the National  Institute  of Diabetes  and  Digestive  and  Kidney  Diseases;  grant  no. UL1RR024992  from  the  National  Center  for  Research Resources,  a  component  of  the  National  Institutes  of Health  and  its  Roadmap  for  Medical  Research;  and  the Taylor Family Institute for Innovative Psychiatric Research. Special thanks to Amanda Ricchio for administrative assistance and to Katie Keenoy for assistance with manuscript development.

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