Guanfacine for the Treatment of Hyperactivity in Pervasive Developmental Disorder

Emory University, Massachusetts General Hospital, Seattle Children's Hospital, University of California, Los Angeles, National Institute of Mental Health (NIMH)

The purpose of this study is to determine whether guanfacine (trade name Intuniv) by itself or in combination with methylphenidate (also known as Ritalin) is helpful for treating hyperactivity in children and adolescents with a Pervasive Developmental Disorders (PDDs).

Pervasive Developmental Disorders (PDDs) are a group of conditions that includes Autistic Disorder, Asperger's disorder and so called Pervasive Developmental Disorder - Not Otherwise Specified. Children with PDD show delays in speech and language and reduced social interaction. Some children with PDD have also have problems with overactivity, impulsiveness and distractability. These behaviors are seen in children with Attention Deficit Hyperactivity Disorder (ADHD). Extended release guanfacine (Intuniv) is FDA-approved for the treatment of children with ADHD. The purpose of this study is to evaluate whether Intuniv is an effective treatment for ADHD symptoms in children with PDD. This study has four parts: an 8-week double-blind trial, an 8-week blinded extension phase (for positive responders only), an 8-week open-label trial, and a 4-week add-on study. Following confirmation of eligibility, participants will be randomly assigned to receive either guanfacine or placebo in the 8-week double-blind trial. Children who show improvement after 8 weeks of treatment will continue on their assigned treatment for an additional 8 weeks (blinded extension phase). Children who show partial improvement with guanfacine will be offered 4 weeks of treatment with guanfacine plus methylphenidate (add-on study). Children who show no improvement on placebo will be offered 8 weeks of treatment with guanfacine (open-label trial). Children who show no improvement on guanfacine will exit the study. Side effects and treatment response will be assessed at regularly scheduled visits. The study protocol was formally revised with the Yale University IRB in May 2013 to address an early close to enrollment due to a reduction in funding. The original anticipated enrollment numbers of 112 subjects was reduced to 60 subjects. The study statistician was consulted prior to enrollment closure to address any issues related to statistical power and the adjustments made to the final statiscal analysis plan.

Pervasive Developmental Disorders, PDD, PDD-NOS, Autistic Disorder, Autism, Asperger's Disorder, Hyperactivity, Attention Deficit Hyperactivity Disorder, ADHD, Medication, Drug, Guanfacine, Intuniv, Placebo, Methylphenidate

The Aberrant Behavior Checklist (ABC) is a symptom checklist for assessing problem behaviors in individuals ages 6 to 54 with mental retardation. The full ABC is a 58-item parent-rating with five factors: Irritability, Social Withdrawal, Stereotypy, Hyperactivity and Inappropriate Speech. The 16-item Hyperactivity subscale covers over-activity (7 items), impulsiveness (2 items), inattention (3 items) and noncompliance (4 items). It has been used as a primary outcome measure in several trials of children with developmental disabilities. The interpretation of the tool and its sub-scales is that a greater number of items, indicates greater severity. The range of scores is 0 to 48.

The ADHD Rating Scale (ADHD-RS) is an 18-item scale directly derived from DSM-IV criteria for Attention Deficit Hyperactivity Disorder with established reliability, validity and sensitivity to change. The ADHD Rating Scale-IV is completed independently by the parent and scored by a clinician. The scale consists of 2 subscales: inattention (9 items) and hyperactivity-impulsivity (9 items). If 3 or more items are skipped, the clinician should use extreme caution in interpreting the scale. Results from this rating scale alone should not be used to make a diagnosis. The total score can range from 0 to 54, with a higher score indicating greater severity.

The Aberrant Behavior Checklist (ABC) is a symptom checklist for assessing problem behaviors in individuals ages 6 to 54 with mental retardation. It is a 58 item checklist which takes about 10 - 15 minutes to complete. There are five subscales: a) Irritability and Agitation b) Lethargy and Social Withdrawal c) Stereotypic Behavior d) Hyperactivity and Noncompliance and e) Inappropriate Speech. The higher the number of items (score), the greater the amount of symptoms. Scores can range from 0 to 45.

The Aberrant Behavior Checklist (ABC) is a symptom checklist for assessing problem behaviors in individuals ages 6 to 54 with mental retardation. The full ABC is a 58-item parent-rating with five factors: Irritability, Social Withdrawal, Stereotypy, Hyperactivity and Inappropriate Speech. It has been used as a primary outcome measure in several trials of children with developmental disabilities. The interpretation of the tool and its sub-scales is that a greater number of items, indicates greater severity. This subscale's scores can range from 0 to 48.

The Aberrant Behavior Checklist (ABC) is a symptom checklist for assessing problem behaviors in individuals ages 6 to 54 with mental retardation. The full ABC is a 58-item parent-rating with five factors: Irritability, Social Withdrawal, Stereotypy, Hyperactivity and Inappropriate Speech. It has been used as a primary outcome measure in several trials of children with developmental disabilities. The interpretation of the tool and its sub-scales is that a greater number of items, indicates greater severity. This subscale's scores can range from 0 to 21.

The Aberrant Behavior Checklist (ABC) is a symptom checklist for assessing problem behaviors in individuals ages 6 to 54 with mental retardation. The full ABC is a 58-item parent-rating with five factors: Irritability, Social Withdrawal, Stereotypy, Hyperactivity and Inappropriate Speech. It has been used as a primary outcome measure in several trials of children with developmental disabilities. The interpretation of the tool and its sub-scales is that a greater number of items, indicates greater severity. This subscale's scores can range from 0 to 12.

The ADHD Rating Scale (ADHD-RS) is an 18-item scale directly derived from DSM-IV criteria for Attention Deficit Hyperactivity Disorder with established reliability, validity and sensitivity to change. The ADHD Rating Scale-IV is completed independently by the parent and scored by a clinician. The scale consists of 2 subscales: inattention (9 items) and hyperactivity-impulsivity (9 items). If 3 or more items are skipped, the clinician should use extreme caution in interpreting the scale. Results from this rating scale alone should not be used to make a diagnosis. This subscale can range from 0 to 27 for scoring, with a higher score indicating greater severity.

The ADHD Rating Scale (ADHD-RS) is an 18-item scale directly derived from DSM-IV criteria for Attention Deficit Hyperactivity Disorder with established reliability, validity and sensitivity to change. The ADHD Rating Scale-IV is completed independently by the parent and scored by a clinician. The scale consists of 2 subscales: inattention (9 items) and hyperactivity-impulsivity (9 items). If 3 or more items are skipped, the clinician should use extreme caution in interpreting the scale. Results from this rating scale alone should not be used to make a diagnosis. This subscale can range from 0 to 27 for scoring,with a higher score indicating greater severity.

The Aberrant Behavior Checklist (ABC) is a symptom checklist for assessing problem behaviors in individuals ages 6 to 54 with mental retardation. The full ABC is a 58-item parent-rating with five factors: Irritability, Social Withdrawal, Stereotypy, Hyperactivity and Inappropriate Speech. The 16-item Hyperactivity subscale covers over-activity (7 items), impulsiveness (2 items), inattention (3 items) and noncompliance (4 items). It has been used as a primary outcome measure in several trials of children with developmental disabilities. The interpretation of the tool and its sub-scales is that a greater number of items, indicates greater severity. The range of scores is 0 to 48.

The Aberrant Behavior Checklist (ABC) is a symptom checklist for assessing problem behaviors in individuals ages 6 to 54 with mental retardation. The full ABC is a 58-item parent-rating with five factors: Irritability, Social Withdrawal, Stereotypy, Hyperactivity and Inappropriate Speech. It has been used as a primary outcome measure in several trials of children with developmental disabilities. The interpretation of the tool and its sub-scales is that a greater number of items, indicates greater severity. Scores for this subscale can range from 0 to 45.

The Aberrant Behavior Checklist (ABC) is a symptom checklist for assessing problem behaviors in individuals ages 6 to 54 with mental retardation. The full ABC is a 58-item parent-rating with five factors: Irritability, Social Withdrawal, Stereotypy, Hyperactivity and Inappropriate Speech. It has been used as a primary outcome measure in several trials of children with developmental disabilities. The interpretation of the tool and its sub-scales is that a greater number of items, indicates greater severity. This subscale's scores can range from 0 to 48.

The Aberrant Behavior Checklist (ABC) is a symptom checklist for assessing problem behaviors in individuals ages 6 to 54 with mental retardation. The full ABC is a 58-item parent-rating with five factors: Irritability, Social Withdrawal, Stereotypy, Hyperactivity and Inappropriate Speech. It has been used as a primary outcome measure in several trials of children with developmental disabilities. The interpretation of the tool and its sub-scales is that a greater number of items, indicates greater severity. This subscale's scores can range from 0 to 21.

The Aberrant Behavior Checklist (ABC) is a symptom checklist for assessing problem behaviors in individuals ages 6 to 54 with mental retardation. The full ABC is a 58-item parent-rating with five factors: Irritability, Social Withdrawal, Stereotypy, Hyperactivity and Inappropriate Speech. It has been used as a primary outcome measure in several trials of children with developmental disabilities. The interpretation of the tool and its sub-scales is that a greater number of items, indicates greater severity. This subscale's scores can range from 0 to 12.

The ADHD Rating Scale (ADHD-RS) is an 18-item scale directly derived from DSM-IV criteria for Attention Deficit Hyperactivity Disorder with established reliability, validity and sensitivity to change. The ADHD Rating Scale-IV is completed independently by the parent and scored by a clinician. The scale consists of 2 subscales: inattention (9 items) and hyperactivity-impulsivity (9 items). If 3 or more items are skipped, the clinician should use extreme caution in interpreting the scale. Results from this rating scale alone should not be used to make a diagnosis. This subscale can range from 0 to 27 for scoring, with a higher score indicating greater severity.

The ADHD Rating Scale (ADHD-RS) is an 18-item scale directly derived from DSM-IV criteria for Attention Deficit Hyperactivity Disorder with established reliability, validity and sensitivity to change. The ADHD Rating Scale-IV is completed independently by the parent and scored by a clinician. The scale consists of 2 subscales: inattention (9 items) and hyperactivity-impulsivity (9 items). If 3 or more items are skipped, the clinician should use extreme caution in interpreting the scale. Results from this rating scale alone should not be used to make a diagnosis. This subscale can range from 0 to 27 for scoring, with a higher score indicating greater severity.

The ADHD Rating Scale (ADHD-RS) is an 18-item scale directly derived from DSM-IV criteria for Attention Deficit Hyperactivity Disorder with established reliability, validity and sensitivity to change. The ADHD Rating Scale-IV is completed independently by the parent and scored by a clinician. The scale consists of 2 subscales: inattention (9 items) and hyperactivity-impulsivity (9 items). If 3 or more items are skipped, the clinician should use extreme caution in interpreting the scale. Results from this rating scale alone should not be used to make a diagnosis. The total score can range from 0 to 54, with a higher score indicating greater severity.

Inclusion Criteria: Diagnosis of PDD (PDD-NOS, Asperger's Disorder, Autistic Disorder) Hyperactivity Between ages 5 years 0 months and 13 years 11 months. Weight >/= 15 kg (33 lb) A mental age of at least 18 months Exclusion Criteria: Prior failed treatment with an adequate trial of guanfacine in the last 2 years Concurrent treatment with another psychoactive medication

Scahill L, Aman MG, McDougle CJ, McCracken JT, Tierney E, Dziura J, Arnold LE, Posey D, Young C, Shah B, Ghuman J, Ritz L, Vitiello B. A prospective open trial of guanfacine in children with pervasive developmental disorders. J Child Adolesc Psychopharmacol. 2006 Oct;16(5):589-98. doi: 10.1089/cap.2006.16.589.