Aggression, Attention Deficit-Hyperactivity, Bipolar Disorder, Oppositional Defiant Disorder, Pervasive Development Disorders
Conditions
Keywords
Antipsychotic treatment, Insulin action/secretion, Abdominal fat mass, total body fat, Aggression, Resting metabolic rates
Brief summary
The project aims to describe and compare the outcome of 12 weeks of prospective, randomized treatment with olanzapine, risperidone or aripiprazole on insulin action in skeletal muscle, liver and adipose tissue, abdominal fat mass, total body and fat-free mass, efficacy for symptoms of aggression and non-metabolic adverse events. Children aged 6-18 will be studied, exploring effects of stimulant therapy and age-related differences in vulnerability to treatment-induced adverse metabolic changes. Aims are addressed by measuring glucose and lipid kinetics with stable isotope tracers, body composition with dual energy x-ray absorptiometry and magnetic resonance imaging (MRI), and standardized assessments of efficacy and adverse events. Relevant data are critically needed to target clinical therapy and basic research, identify medical risks, and guide regulatory decisions in this vulnerable population.
Detailed description
This randomized clinical trial assesses both the safety and efficacy of atypical antipsychotic agents in antipsychotic-naive aggressive children with various childhood psychiatric disorders during 12 weeks of prospective, randomized treatment with olanzapine, risperidone or aripiprazole. Aim 1: To evaluate effects of selected antipsychotic treatments on insulin action in muscle (glucose disposal), liver (glucose production) and adipose tissue (lipolysis). Aim 2: To evaluate effects of selected antipsychotic treatments on abdominal fat mass, total body fat and total fat-free mass.
Interventions
DRUGrisperidone
randomized to begin 12 week trial of risperidone
DRUGolanzapine
randomized to begin 12 week trial of olanzapine
DRUGaripiprazole
randomized to 12 week trial of aripiprazole
Sponsors
National Institute of Mental Health (NIMH)
Washington University School of Medicine
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
SINGLE (Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
6 Years to 18 Years
Healthy volunteers
No
Inclusion criteria
* Aged 6-18 years * Generally healthy and a score of ≥ 18 on the Aberrant Behavior Checklist in the context of one or more Axis I Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV) childhood psychiatric disorders, including conduct disorder, oppositional defiant disorder, disruptive behavior disorder, autism, pervasive developmental disorder, attention deficit disorder, schizophrenia and bipolar affective disorders * Children's Global Assessment Scale (CGAS) score ≤ 60 * Not previously treated with an antipsychotic; individual subjects with remote, brief prior antipsychotic exposure may be considered for enrollment by the PI on a case by case basis * Patient assent and informed consent obtained from the parent or guardian * No clinically significant (based on PI determination) changes in permitted medications (e.g., stimulants and selective serotonin reuptake inhibitors \[SSRIs\]) for approximately 1 month prior to Baseline evaluations
Exclusion criteria
* Active suicidality or primary dx of major depressive disorder * Any lifetime use of antipsychotics or non-serotonin selective reuptake inhibitor (non-SSRI) anti-depressants * The presence of any serious medical disorder, based on PI determination, that may confound the assessment of relevant biologic measures or diagnoses, including: * significant organ system dysfunction; * endocrine disease, including type 1 or type 2 diabetes mellitus; * coagulopathy; * anemia; * or acute infection. * Subjects regularly taking any glucose lowering agent, lipid lowering agent, exogenous testosterone, recombinant human growth hormone, or any other endocrine agent that might confound substrate metabolism, oral glucocorticoids (glucocorticoid inhalants and nasal sprays are permitted), antihistamines, sedating antihistamines (non-sedating antihistamines such as but not limited to Claritin (loratadine) and Zyrtec (cetirizine) are permitted), and certain mood stabilizing agents, as some medications may themselves worsen or otherwise alter weight gain, glucose and lipid regulation or otherwise make it difficult to assess the effects of the antipsychotic alone; (note that exposure to many psychotropic agents including stimulants and SSRI's is permitted in order to maintain the generalizability of the sample); * Intelligence quotient (IQ) \< 70 (based on school records and/or evaluation by clinician) * current substance abuse * Past history or currently has dyskinesia * Stimulant dosage significantly higher (per PI judgment)than the equivalent of approximately 2mg/kg/day methylphenidate equivalent dose.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in DEXA % Body Fat | 12 weeks | This study hypothesized that antipsychotic treatment would increase percent total body fat, as measured by whole body dual energy x-ray absorptiometry (DEXA), with larger adverse effects for olanzapine. |
| Change in Insulin-stimulated Glucose Rate of Disappearance (Glucose Rd) | 12 weeks | This study hypothesized that antipsychotic treatment would decrease insulin sensitivity at muscle, as measured by the insulin-stimulated rate of disappearance of glucose (glucose Rd), with larger adverse effects for olanzapine. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in Insulin-stimulated Glycerol Rate of Appearance (Glycerol Ra) | 12 weeks | This study hypothesized that antipsychotic treatment would decrease insulin sensitivity at adipose tissue, as measured by the insulin-stimulated rate of disappearance of glycerol (glycerol Ra), with larger adverse effects for olanzapine. |
| Change in Insulin-stimulated Glucose Rate of Appearance (Glucose Ra) | 12 weeks | This study hypothesized that antipsychotic treatment would decrease hepatic insulin sensitivity, as measured by the rate of appearance of glucose (glucose Ra), with larger adverse effects for olanzapine. |
| Change in MRI-measured Visceral Abdominal Fat | 12 weeks | This study hypothesized that antipsychotic treatment would increase visceral abdominal fat, as measured by abdominal magnetic resonance imaging (MRI), with larger adverse effects for olanzapine. |
| Change in MRI-measured Subcutaneous Abdominal Fat | 12 weeks | This study hypothesized that antipsychotic treatment would increase subcutaneous abdominal fat, as measured by abdominal magnetic resonance imaging (MRI), with larger adverse effects for olanzapine. |
Countries
United States
Participant flow
Pre-assignment details
Post-enrollment screening for inclusion and exclusion criteria, e.g. for exclusionary conditions like diabetes mellitus.
Participants by arm
| Arm | Count |
|---|---|
| Risperidone 12 weeks randomized, flexibly-dosed treatment with risperidone | 49 |
| Olanzapine 12 weeks randomized, flexibly-dosed treatment with olanzapine | 46 |
| Aripiprazole 12 weeks randomized, flexibly-dosed treatment with aripiprazole | 49 |
| Total | 144 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Adverse Event | 1 | 0 | 0 |
| Overall Study | Lack of Efficacy | 0 | 1 | 0 |
| Overall Study | Lost to Follow-up | 1 | 3 | 5 |
| Overall Study | Withdrawal by Subject | 1 | 2 | 1 |
Baseline characteristics
| Characteristic | Aripiprazole | Olanzapine | Risperidone | Total |
|---|---|---|---|---|
| Aberrant Behavioral Checklist Subscales Hyperactivity | 32.80 units on a scale STANDARD_DEVIATION 10.88 | 32.11 units on a scale STANDARD_DEVIATION 10.45 | 32.83 units on a scale STANDARD_DEVIATION 9.68 | 32.59 units on a scale STANDARD_DEVIATION 10.28 |
| Aberrant Behavioral Checklist Subscales Inappropriate Speech | 3.69 units on a scale STANDARD_DEVIATION 2.76 | 3.78 units on a scale STANDARD_DEVIATION 2.71 | 4.60 units on a scale STANDARD_DEVIATION 3.02 | 4.03 units on a scale STANDARD_DEVIATION 2.85 |
| Aberrant Behavioral Checklist Subscales Irritability/Aggression | 28.14 units on a scale STANDARD_DEVIATION 6.27 | 28.17 units on a scale STANDARD_DEVIATION 5.73 | 28.49 units on a scale STANDARD_DEVIATION 5.53 | 28.27 units on a scale STANDARD_DEVIATION 5.81 |
| Aberrant Behavioral Checklist Subscales Lethargy | 14.61 units on a scale STANDARD_DEVIATION 8.83 | 12.67 units on a scale STANDARD_DEVIATION 8.15 | 16.57 units on a scale STANDARD_DEVIATION 10.01 | 14.66 units on a scale STANDARD_DEVIATION 9.12 |
| Aberrant Behavioral Checklist Subscales Stereotypy | 4.29 units on a scale STANDARD_DEVIATION 4.61 | 5.15 units on a scale STANDARD_DEVIATION 4.42 | 5.54 units on a scale STANDARD_DEVIATION 4.95 | 4.99 units on a scale STANDARD_DEVIATION 4.67 |
| Aberrant Behavioral Checklist Subscales Total | 83.53 units on a scale STANDARD_DEVIATION 25.7 | 81.89 units on a scale STANDARD_DEVIATION 21.55 | 88.03 units on a scale STANDARD_DEVIATION 23.96 | 84.54 units on a scale STANDARD_DEVIATION 23.82 |
| Age, Continuous | 11.60 years STANDARD_DEVIATION 2.92 | 11.10 years STANDARD_DEVIATION 2.52 | 11.32 years STANDARD_DEVIATION 2.95 | 11.35 years STANDARD_DEVIATION 2.79 |
| Baseline fasting laboratory values (g/dL) Albumin | 4.05 g/dL STANDARD_DEVIATION 0.25 | 4.06 g/dL STANDARD_DEVIATION 0.27 | 4.02 g/dL STANDARD_DEVIATION 0.25 | 4.05 g/dL STANDARD_DEVIATION 0.25 |
| Baseline fasting laboratory values (g/dL) Total Protein | 6.95 g/dL STANDARD_DEVIATION 0.34 | 6.90 g/dL STANDARD_DEVIATION 0.39 | 6.95 g/dL STANDARD_DEVIATION 0.46 | 6.94 g/dL STANDARD_DEVIATION 0.4 |
| Baseline Fasting Laboratory Values (IU/L) Alanine aminotransferase (ALT) | 15.53 IU/L STANDARD_DEVIATION 4.49 | 13.83 IU/L STANDARD_DEVIATION 4.2 | 18.10 IU/L STANDARD_DEVIATION 7.74 | 15.86 IU/L STANDARD_DEVIATION 5.96 |
| Baseline Fasting Laboratory Values (IU/L) Alkaline Phosphatase | 206.41 IU/L STANDARD_DEVIATION 85.35 | 222.54 IU/L STANDARD_DEVIATION 75.69 | 209.33 IU/L STANDARD_DEVIATION 88.42 | 212.56 IU/L STANDARD_DEVIATION 83.19 |
| Baseline Fasting Laboratory Values (IU/L) Aspartate aminostransferase (AST) | 23.94 IU/L STANDARD_DEVIATION 6.78 | 23.26 IU/L STANDARD_DEVIATION 6.12 | 25.65 IU/L STANDARD_DEVIATION 7.1 | 24.31 IU/L STANDARD_DEVIATION 6.72 |
| Baseline fasting laboratory values (mg/dL) Fasting Glucose | 88.98 mg/dL STANDARD_DEVIATION 6.16 | 87.48 mg/dL STANDARD_DEVIATION 6.55 | 89.14 mg/dL STANDARD_DEVIATION 8.81 | 88.56 mg/dL STANDARD_DEVIATION 7.27 |
| Baseline fasting laboratory values (mg/dL) LDL Cholesterol | 72.82 mg/dL STANDARD_DEVIATION 26 | 72.00 mg/dL STANDARD_DEVIATION 24.56 | 79.53 mg/dL STANDARD_DEVIATION 25.41 | 74.84 mg/dL STANDARD_DEVIATION 25.4 |
| Baseline fasting laboratory values (mg/dL) Total Bilirubin | 0.33 mg/dL STANDARD_DEVIATION 0.18 | 0.40 mg/dL STANDARD_DEVIATION 0.18 | 0.37 mg/dL STANDARD_DEVIATION 0.25 | 0.37 mg/dL STANDARD_DEVIATION 0.21 |
| Baseline fasting laboratory values (mg/dL) Total Cholesterol | 135.45 mg/dL STANDARD_DEVIATION 28.34 | 137.09 mg/dL STANDARD_DEVIATION 25.31 | 144.74 mg/dL STANDARD_DEVIATION 28.88 | 139.14 mg/dL STANDARD_DEVIATION 27.71 |
| Baseline fasting laboratory values (mg/dL) Triglycerides | 52.16 mg/dL STANDARD_DEVIATION 23.13 | 60.98 mg/dL STANDARD_DEVIATION 31.89 | 60.40 mg/dL STANDARD_DEVIATION 33 | 57.78 mg/dL STANDARD_DEVIATION 29.69 |
| Baseline Insulin Stimulated % Change in Isotopomer Measurement during Week 0 Clamp % Change in Glucose Rate of Appearance | 82.70 % change during baseline clamp STANDARD_DEVIATION 12.15 | 82.53 % change during baseline clamp STANDARD_DEVIATION 9.9 | 83.19 % change during baseline clamp STANDARD_DEVIATION 10.94 | 82.83 % change during baseline clamp STANDARD_DEVIATION 11.01 |
| Baseline Insulin Stimulated % Change in Isotopomer Measurement during Week 0 Clamp % Change in Glucose Rate of Disappearance | 156.49 % change during baseline clamp STANDARD_DEVIATION 81.14 | 168.75 % change during baseline clamp STANDARD_DEVIATION 82.09 | 166.26 % change during baseline clamp STANDARD_DEVIATION 78.79 | 163.56 % change during baseline clamp STANDARD_DEVIATION 80.06 |
| Baseline Insulin Stimulated % Change in Isotopomer Measurement during Week 0 Clamp % Change in Glycerol Rate of Appearance | 50.46 % change during baseline clamp STANDARD_DEVIATION 15.04 | 55.94 % change during baseline clamp STANDARD_DEVIATION 15.08 | 55.59 % change during baseline clamp STANDARD_DEVIATION 13.42 | 53.89 % change during baseline clamp STANDARD_DEVIATION 14.59 |
| Baseline Insulin Stimulated % Change in Isotopomer Measurement during Week 0 Clamp Whole Body Sensitivity | 12.87 % change during baseline clamp STANDARD_DEVIATION 6.36 | 12.53 % change during baseline clamp STANDARD_DEVIATION 4.47 | 12.96 % change during baseline clamp STANDARD_DEVIATION 5.33 | 12.80 % change during baseline clamp STANDARD_DEVIATION 5.44 |
| Body Mass Index Percentile | 63.05 percentile STANDARD_DEVIATION 30.12 | 58.38 percentile STANDARD_DEVIATION 31.33 | 62.13 percentile STANDARD_DEVIATION 29.7 | 61.25 percentile STANDARD_DEVIATION 30.22 |
| Body Mass index z-score | 0.55 z-score STANDARD_DEVIATION 1.13 | 0.30 z-score STANDARD_DEVIATION 1.11 | 0.49 z-score STANDARD_DEVIATION 1.12 | 0.45 z-score STANDARD_DEVIATION 1.12 |
| Body Weight | 47.94 kilograms STANDARD_DEVIATION 23.57 | 42.23 kilograms STANDARD_DEVIATION 13.81 | 45.49 kilograms STANDARD_DEVIATION 19.08 | 45.28 kilograms STANDARD_DEVIATION 19.34 |
| Clinical Global Assessment of Functioning | 50.88 units on a scale STANDARD_DEVIATION 6 | 50.67 units on a scale STANDARD_DEVIATION 5.44 | 51.71 units on a scale STANDARD_DEVIATION 4.44 | 51.10 units on a scale STANDARD_DEVIATION 5.31 |
| Clinical Global Improvement (CGI)-Severity of Illness Markedly ill | 23 participants | 26 participants | 31 participants | 80 participants |
| Clinical Global Improvement (CGI)-Severity of Illness Moderately ill | 23 participants | 19 participants | 18 participants | 60 participants |
| Clinical Global Improvement (CGI)-Severity of Illness Severely ill | 3 participants | 1 participants | 0 participants | 4 participants |
| DEXA-measured body composition (%) DEXA Total % Fat | 26.23 percentage of body composition STANDARD_DEVIATION 10.83 | 24.48 percentage of body composition STANDARD_DEVIATION 10.19 | 26.25 percentage of body composition STANDARD_DEVIATION 10.64 | 25.68 percentage of body composition STANDARD_DEVIATION 10.52 |
| DEXA-measured body composition (%) DEXA Total % Lean | 70.32 percentage of body composition STANDARD_DEVIATION 10.53 | 71.96 percentage of body composition STANDARD_DEVIATION 9.96 | 70.30 percentage of body composition STANDARD_DEVIATION 10.35 | 70.84 percentage of body composition STANDARD_DEVIATION 10.25 |
| DEXA-measured body composition (kg) DEXA Total Fat kg | 13.24 kilograms STANDARD_DEVIATION 10.4 | 10.46 kilograms STANDARD_DEVIATION 6.68 | 12.50 kilograms STANDARD_DEVIATION 9.53 | 12.10 kilograms STANDARD_DEVIATION 9.07 |
| DEXA-measured body composition (kg) DEXA Total Lean kg | 31.98 kilograms STANDARD_DEVIATION 14.69 | 29.30 kilograms STANDARD_DEVIATION 9.83 | 30.38 kilograms STANDARD_DEVIATION 11.01 | 30.58 kilograms STANDARD_DEVIATION 12.04 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 1 Participants | 1 Participants | 2 Participants | 4 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 48 Participants | 45 Participants | 47 Participants | 140 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Fasting Insulin | 9.00 uU/mL STANDARD_DEVIATION 8.68 | 6.24 uU/mL STANDARD_DEVIATION 3.74 | 7.64 uU/mL STANDARD_DEVIATION 5.85 | 7.65 uU/mL STANDARD_DEVIATION 6.5 |
| Hemoglobin A1c | 5.54 % STANDARD_DEVIATION 0.28 | 5.54 % STANDARD_DEVIATION 0.34 | 5.46 % STANDARD_DEVIATION 0.26 | 5.52 % STANDARD_DEVIATION 0.29 |
| High Sensitivity c-Reactive Protein (HS-CRP) | 1.12 mg/L STANDARD_DEVIATION 1.53 | 1.37 mg/L STANDARD_DEVIATION 3.04 | 1.61 mg/L STANDARD_DEVIATION 3.04 | 1.37 mg/L STANDARD_DEVIATION 2.62 |
| MRI-measured abdominal fat MRI Subcutaneous Fat | 111.16 cm squared STANDARD_DEVIATION 94.16 | 86.17 cm squared STANDARD_DEVIATION 65.1 | 121.38 cm squared STANDARD_DEVIATION 123.05 | 107.23 cm squared STANDARD_DEVIATION 98.53 |
| MRI-measured abdominal fat MRI Total Fat | 137.85 cm squared STANDARD_DEVIATION 116.24 | 106.09 cm squared STANDARD_DEVIATION 82.28 | 147.17 cm squared STANDARD_DEVIATION 137.36 | 131.56 cm squared STANDARD_DEVIATION 115.76 |
| MRI-measured abdominal fat MRI Visceral Fat | 26.70 cm squared STANDARD_DEVIATION 24.14 | 19.37 cm squared STANDARD_DEVIATION 19.74 | 25.79 cm squared STANDARD_DEVIATION 18.45 | 24.11 cm squared STANDARD_DEVIATION 20.96 |
| Number of Suspensions | 2.85 number of discrete school suspensions STANDARD_DEVIATION 4.18 | 2.71 number of discrete school suspensions STANDARD_DEVIATION 3.98 | 2.60 number of discrete school suspensions STANDARD_DEVIATION 4.11 | 2.72 number of discrete school suspensions STANDARD_DEVIATION 4.07 |
| On Selective Serotonin Reuptake Inhibitors (SSRI) No | 45 participants | 41 participants | 41 participants | 127 participants |
| On Selective Serotonin Reuptake Inhibitors (SSRI) Yes | 4 participants | 5 participants | 8 participants | 17 participants |
| On stimulant No | 27 participants | 25 participants | 20 participants | 72 participants |
| On stimulant Yes | 22 participants | 21 participants | 29 participants | 72 participants |
| Primary Diagnosis Attention Deficit Hyperactivity Disorder | 29 participants | 23 participants | 28 participants | 80 participants |
| Primary Diagnosis Autism Spectrum Disorder | 3 participants | 4 participants | 3 participants | 10 participants |
| Primary Diagnosis Disruptive Behavior Disorder | 13 participants | 11 participants | 8 participants | 32 participants |
| Primary Diagnosis Mood Disorder | 4 participants | 5 participants | 7 participants | 16 participants |
| Primary Diagnosis Obsessive Compulsive Disorder | 0 participants | 1 participants | 0 participants | 1 participants |
| Primary Diagnosis Psychosis | 0 participants | 2 participants | 2 participants | 4 participants |
| Primary Diagnosis Tourette Disorder | 0 participants | 0 participants | 1 participants | 1 participants |
| Race/Ethnicity, Customized Non-White | 30 participants | 24 participants | 25 participants | 79 participants |
| Race/Ethnicity, Customized White | 19 participants | 22 participants | 24 participants | 65 participants |
| Sex: Female, Male Female | 15 Participants | 18 Participants | 13 Participants | 46 Participants |
| Sex: Female, Male Male | 34 Participants | 28 Participants | 36 Participants | 98 Participants |
| Waist Circumference | 69.54 centimeters STANDARD_DEVIATION 15.5 | 65.87 centimeters STANDARD_DEVIATION 11.03 | 68.72 centimeters STANDARD_DEVIATION 13.47 | 68.09 centimeters STANDARD_DEVIATION 13.5 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 49 | 0 / 46 | 0 / 49 |
| other Total, other adverse events | 38 / 49 | 38 / 46 | 39 / 49 |
| serious Total, serious adverse events | 0 / 49 | 0 / 46 | 1 / 49 |
Outcome results
Primary
Change in DEXA % Body Fat
This study hypothesized that antipsychotic treatment would increase percent total body fat, as measured by whole body dual energy x-ray absorptiometry (DEXA), with larger adverse effects for olanzapine.
Time frame: 12 weeks
Population: Modified Intent to Treat (ITT) sample with week 0 and week 12 data.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Risperidone | Change in DEXA % Body Fat | 1.81 percent body fat | Standard Deviation 3.11 |
| Olanzapine | Change in DEXA % Body Fat | 4.12 percent body fat | Standard Deviation 3.1 |
| Aripiprazole | Change in DEXA % Body Fat | 1.66 percent body fat | Standard Deviation 2.65 |
Comparison: Primary analysis for change in DEXA % fat used a likelihood-based mixed-effects model using time (0, 6 and 12 weeks) and medication group as independent variables, with Toeplitz covariance structure specified, based on Bayesian information criteria (BIC). The null hypotheses were that there was no difference in the outcome over time (main effect of time) and that there were no differences between groups in the change over time (time by treatment condition).p-value: <0.0001Mixed Models Analysis
Primary
Change in Insulin-stimulated Glucose Rate of Disappearance (Glucose Rd)
This study hypothesized that antipsychotic treatment would decrease insulin sensitivity at muscle, as measured by the insulin-stimulated rate of disappearance of glucose (glucose Rd), with larger adverse effects for olanzapine.
Time frame: 12 weeks
Population: Children ages 6-18 with a Diagnostic and Statistical Manual Text Revision (DSM-IV-TR) diagnosis and clinically significant aggression or irritability
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Risperidone | Change in Insulin-stimulated Glucose Rate of Disappearance (Glucose Rd) | 2.30 percentage of % change | Standard Deviation 83.91 |
| Olanzapine | Change in Insulin-stimulated Glucose Rate of Disappearance (Glucose Rd) | -29.34 percentage of % change | Standard Deviation 85.56 |
| Aripiprazole | Change in Insulin-stimulated Glucose Rate of Disappearance (Glucose Rd) | -30.26 percentage of % change | Standard Deviation 65.46 |
p-value: 0.07ANCOVA
Secondary
Change in Insulin-stimulated Glucose Rate of Appearance (Glucose Ra)
This study hypothesized that antipsychotic treatment would decrease hepatic insulin sensitivity, as measured by the rate of appearance of glucose (glucose Ra), with larger adverse effects for olanzapine.
Time frame: 12 weeks
Population: Modified Intent to Treat (ITT) sample with week 0 and week 12 data.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Risperidone | Change in Insulin-stimulated Glucose Rate of Appearance (Glucose Ra) | -2.50 percentage of % change | Standard Deviation 7.61 |
| Olanzapine | Change in Insulin-stimulated Glucose Rate of Appearance (Glucose Ra) | -6.57 percentage of % change | Standard Deviation 13.16 |
| Aripiprazole | Change in Insulin-stimulated Glucose Rate of Appearance (Glucose Ra) | -3.27 percentage of % change | Standard Deviation 9.27 |
p-value: 0.17ANCOVA
Secondary
Change in Insulin-stimulated Glycerol Rate of Appearance (Glycerol Ra)
This study hypothesized that antipsychotic treatment would decrease insulin sensitivity at adipose tissue, as measured by the insulin-stimulated rate of disappearance of glycerol (glycerol Ra), with larger adverse effects for olanzapine.
Time frame: 12 weeks
Population: Modified Intent to Treat (ITT) sample with week 0 and week 12 data.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Risperidone | Change in Insulin-stimulated Glycerol Rate of Appearance (Glycerol Ra) | -3.65 percentage of % change | Standard Deviation 17.23 |
| Olanzapine | Change in Insulin-stimulated Glycerol Rate of Appearance (Glycerol Ra) | -8.29 percentage of % change | Standard Deviation 22.39 |
| Aripiprazole | Change in Insulin-stimulated Glycerol Rate of Appearance (Glycerol Ra) | 1.70 percentage of % change | Standard Deviation 16.79 |
p-value: 0.27ANCOVA
Secondary
Change in MRI-measured Subcutaneous Abdominal Fat
This study hypothesized that antipsychotic treatment would increase subcutaneous abdominal fat, as measured by abdominal magnetic resonance imaging (MRI), with larger adverse effects for olanzapine.
Time frame: 12 weeks
Population: Modified Intent to Treat (ITT) sample with week 0 and week 12 data.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Risperidone | Change in MRI-measured Subcutaneous Abdominal Fat | 18.21 Change in cm-squared | Standard Deviation 22.27 |
| Olanzapine | Change in MRI-measured Subcutaneous Abdominal Fat | 34.27 Change in cm-squared | Standard Deviation 27.22 |
| Aripiprazole | Change in MRI-measured Subcutaneous Abdominal Fat | 15.84 Change in cm-squared | Standard Deviation 19.02 |
Comparison: Repeated measures ANCOVA was used to test for the main effect of time on the outcome, and to test for a time by treatment condition interaction that would indicate differences between groups in change over time in the primary outcome. The null hypotheses were that there was no difference in the outcome over time (main effect of time) and that there were no differences between groups in the change over time (time by treatment condition).p-value: <0.003ANCOVA
p-value: 0.003Contrast
p-value: 0.002ANCOVA
Secondary
Change in MRI-measured Visceral Abdominal Fat
This study hypothesized that antipsychotic treatment would increase visceral abdominal fat, as measured by abdominal magnetic resonance imaging (MRI), with larger adverse effects for olanzapine.
Time frame: 12 weeks
Population: Modified Intent to Treat (ITT) sample with week 0 and week 12 data.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Risperidone | Change in MRI-measured Visceral Abdominal Fat | 6.85 Change in cm-squared | Standard Deviation 10.99 |
| Olanzapine | Change in MRI-measured Visceral Abdominal Fat | 10.73 Change in cm-squared | Standard Deviation 14.5 |
| Aripiprazole | Change in MRI-measured Visceral Abdominal Fat | 12.04 Change in cm-squared | Standard Deviation 15.11 |
p-value: 0.29ANCOVA