8/4/2019 Wt Predictors NCDEU 2011 Final

1/1

Clinical Predictors of Weight Change During Long-Term Risperidone Treatment

Background:With their prescribing rate rapidly increasing in youths (1),concerns have been raised about the cardio-metabolic effects of atypicalantipsychotics (2). Yet, most studies to date have been of short duration,failing to address the long-term safety of these drugs, particularly whentaken concurrently with other psychotropics, which is often the case inclinical practice.

Objective:To identify predictors of risperidone-induced weight gain in asizeable sample of youths in long-term treatment.

Chadi Calarge, M.D.1; Diqiong Xie, M.S.2, M. Bridget Zimmerman, Ph.D.2The University of Iowa Carver College of Medicine1 and College of Public Health2

Introduction

Methods

Results

Conclusions1. When considered longitudinally, the dose of risperidone is

associated with the extent of weight gain though this effect

attenuates over time.

2. Conversely, psychostimulants, SSRIs, and 2-agonists tend to reduce

weight gain related to risperidone.

3. The faster the weight gain from risperidone the more insulinresistance ensues.

4. Whether these findings apply to other antipsychotics remains to be

seen.

References:1. Olfson M, Blanco C, Liu L, Moreno C, Laje G: National trends in the outpatient treatment of children

and adolescents with antipsychotic drugs. Arch Gen Psychiatry 2006; 63:679-685.2. Correll CU, Manu P, OlshanskiyV, Napolitano B, Kane JM, Malhotra AK: Cardiometabolic risk of

second-generation antipsychotic medications during first-time use in children and adolescents. JAMA2009; 302:1765-1773.

3. Calarge CA, Acion L, Kuperman S, Tansey M, Schlechte JA: Weight gain and metabolic abnormalitiesduring extended risperidone treatment in children and adolescents. J Child Adolesc Psychopharmacol2009a; 19:101-109.

4. Slaughter MH, Lohman TG, Boileau RA, HorswillCA, Stillman RJ, Van Loan MD, Bemben DA:Skinfold equations for estimation of body fatness in children and youth. Hum Biol 1988; 60:709-723.

5. Matthews DR, HoskerJP, RudenskiAS, Naylor BA, TreacherDF, Turner RC: Homeostasis modelassessment: insulin resistance and beta-cell function from fasting plasma glucose and insulinconcentrations in man. Diabetologia 1985; 28:412-419.

Acknowledgements: This work was funded by NARSAD, the National Institute of MentalHealth (R21MH080968 and K23MH085005), andthe National Center for ResearchResources (RR0024979). Contact: chadi-calarge@uiowa.edu

Table 2: Psychiatric Characteristics of the Sample

Characteristic Mean or N SD or %

Psychiatric Diagnoses:

Attention Deficit Hyperactivity Disorder

Disruptive Behavior Disorder

Anxiety Disorder

Tic Disorder

Depressive Disorder

Pervasive Developmental Disorder

Bipolar Disorder

Psychotic Disorder

122

98

53

31

25

21

2

2

84

68

37

21

17

14

1

1

Psychopharmacology:

Risperidone Dose, mg/kg/d

Treatment Duration, yrs

Most Common Concomitant Medications:

PsychostimulantsSSRIs

2-agonists

0.03

2.6

9870

47

0.03

1.7

6848

32

Table1: Demographic and Clinical Characteristics of the Sample

Characteristic Mean or N SD or %

Age, years 11.4 2.8

Males 132 91

Anthropometric Measures:

Baseline Wt z Score (n=105)

Baseline BMI z Score (n=104)

Enrollment Weight z Score

Enrollment Weight z Score

Percent Body Fat

0.1

0.1

0.6

0.6

21.2

1.1

1.1

1.1

1.1

10.1

Laboratory Tests:

Glucose (mg/dl)

Total Insulin (IU/ml)

HOMA-IR

90.2

6.7

1.5

8.35

4.7

1.1

Participants:Healthy, 7 to 17 year-old patients treated with risperidonefor at least six months were enrolled (3). Participants were excluded ifthey were pregnant, received other antipsychotic drugs, or suffered

neurological disorders or chronic medical conditions.

Procedures:Demographic and clinical variables were collected uponenrollment. Available anthropometric measurements and the medication

history were extracted from the medical records. Furthermore, height andweight were measured, at recruitment, following standard procedures (3).Triceps and subscapular skinfold thickness was measured with a Lange

caliper. Insulin and glucose were measured following an overnight fast.In addition, information related to birth weight, dietary intake, physicalactivity, and parental weights/heights was collected.

Statistical Analysis:Weight and body mass index (BMI) were adjusted forage and sex using the US normative data. Body fat content was

estimated using skinfold thickness measurements following Slaughter etal. (4). The homeostasis model assessment insulin resistance index(HOMA-IR) was estimated by the formula: insulin (IU/ml) x glucose

(mg/dl)/405 (5).

Mixed regression analyses explored the independent longitudinal effectof various demographic and clinical factors on the age- and sex-adjusted

weight and BMI z scores over the treatment period. In addition, multiplelinear regression explored the effect of the rate of change in weight (BMI)z scores on HOMA-IR and percent body fat, controlling for weight (BMI) zscore upon enrollment.

A total of 145 participants were included in this analysis, the majorityof whom (79%) received risperidone to target irritability and

aggression. Only 5% (n=7) received risperidone monotherapy.

After controlling for the other significant predictors, SSRI use wasassociated with lower weight gain (=-0.08, p