Side Effect Study of Antipsychotic Medicines to Treat Childhood Bipolar Disorder (PAMS)

Investigating Metabolic Side Effects of Antipsychotic Medications in Children

The purpose of this study is to learn more about weight gain and related side effects when children are treated with antipsychotic medicine for mood disorders.

Study Overview

• Status: Terminated
• Conditions: Bipolar Disorder
• Intervention / Treatment: Drug: risperidone; Drug: aripiprazole

Detailed Description

This protocol is a six month, randomized, open label trial of risperidone versus aripiprazole in antipsychotic naive youth (7 - 12 years old) who have been identified by their clinical treatment provider as needing antipsychotic treatment of a bipolar disorder.

This study proposes to monitor changes in metabolic parameters (body mass index percentile, % body fat, insulin resistance, and lipid levels) over the course of six months treatment with aripiprazole or risperidone in youth with a bipolar spectrum disorder. We will also assess possible mechanisms of second generation antipsychotic induced weight gain by monitoring physical activity and hunger/appetite changes over the course of treatment.

• Study Type: Interventional
• Enrollment (Actual): 5
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Maryland
    • Baltimore, Maryland, United States, 21201
      • University of Maryland, School of Medicine, Department of Psychiatry, Division of Child and Adolescent Psychiatry

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 7 years to 12 years (Child)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• We will include children, ages 7 - 12 years old, male and female with diagnosis of a bipolar spectrum disorder.

• Specific diagnoses included are as follows:

  • Bipolar I disorder,
  • Bipolar II disorder,
  • Bipolar Disorder Not Otherwise Specified,
  • Mood Disorder Not otherwise specified.
• The inclusion of a spectrum of bipolar diagnosis is because children with moderate to severe impairment from mood symptoms often still do not meet criteria for Bipolar I disorder since young children tend to have more chronic (non-episodic) course of symptoms and diagnostic criteria for Bipolar I disorder are more difficult to apply to adults than young children (e.g. symptoms of grandiosity and euphoria).
• No prior treatment with an antipsychotic medication for >30 days. This criteria was added because weight loss on an assigned treatment may be due to discontinuing a prior antipsychotic medication rather than due to the current treatment.
• Recommendation from a current psychiatric treatment provider for treatment with an antipsychotic medication.
• This inclusion criteria provides an added layer of safety in that youth who have referred for the study have already been deemed by their independent provider to need an antipsychotic medication, so we are only exposing children to antipsychotic treatment who would have been treated with this type of medication regardless of whether or not there care was provided in a research or clinical program.

Exclusion Criteria:

• Medications: We will exclude children who are on current treatment with

  • oral steroids,
  • lithium,
  • depakote since these medications will have a confounding effect on weight.
• We will allow children on stimulant medication to participate, because ADHD comorbidity is very high in prepubertal bipolar disorder (unlike adolescent or adult onset bipolar disorder).
• We are including ADHD children to thus increase generalizability of the study, and it would be inappropriate to withhold stimulant treatment from these children for a six month period.
• Recruitment will be stratified to make sure there are equal numbers of patients on stimulants in each group.
• Somatic Conditions: We will exclude children with diabetes (type I or type II), and those with physical disability that would interfere with physical activity (will specifically exclude children whose guardian reports that the child has been medically excused from physical education at their school program because of physical disability) since insulin sensitivity and activity levels are outcome measures being assessed in this protocol.
• We will exclude youth with mental retardation, by parent report. Cognitive screening will be done with the Wechsler Abbreviated Scale of Intelligence (WASI).
• Youth with an IQ less than 70 will be excluded because they may have difficulty with self report measures.
• We will exclude children who have a history of treatment of an antipsychotic medication for >30 days, as explained above.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 1; risperidone	Drug: risperidone; Children will have a flexible dose titration based on their unique response to the medication (assessed using clinical global improvement scores). Children will be treated for six months using daily, bid dosing.; Other Names: Brand name: Risperdal
Experimental: 2; aripiprazole	Drug: aripiprazole; children will have a flexible dosing titration based on their unique response (assessed using clinical global improvement scores). Children will be treated with daily medication for six months.; Other Names: Brand name: Abilify

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Weight Gain	Weight gain from baseline to last observation up to 12 weeks. Last observation carried to 12 weeks.	These measurements are done biweekly from baseline up until 12 weeks

Collaborators and Investigators

• Sponsor: University of Maryland, Baltimore
• Investigators: Principal Investigator: Gloria Reeves, M.D., University of Maryland, Baltimore

Study record dates

Study Major Dates

• Study Start: June 1, 2008
• Primary Completion (Actual): October 1, 2010
• Study Completion (Actual): October 1, 2010

Study Registration Dates

• First Submitted: September 2, 2008
• First Submitted That Met QC Criteria: September 2, 2008
• First Posted (Estimate): September 3, 2008

Study Record Updates

• Last Update Posted (Actual): January 6, 2020
• Last Update Submitted That Met QC Criteria: January 2, 2020
• Last Verified: January 1, 2020

More Information

Terms related to this study

• Keywords: children; antipsychotic; bipolar; side effect
• Additional Relevant MeSH Terms: Mental Disorders; Bipolar and Related Disorders; Bipolar Disorder; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Central Nervous System Depressants; Antipsychotic Agents; Tranquilizing Agents; Psychotropic Drugs; Serotonin Agents; Antidepressive Agents; Dopamine Agonists; Dopamine Agents; Serotonin 5-HT1 Receptor Agonists; Serotonin Receptor Agonists; Serotonin 5-HT2 Receptor Antagonists; Serotonin Antagonists; Dopamine D2 Receptor Antagonists; Dopamine Antagonists; Aripiprazole; Risperidone
• Other Study ID Numbers: HP-00043695

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No