Mirtazapine Treatment of Anxiety in Children and Adolescents With Pervasive Developmental Disorders

Study Overview
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Brief Summary
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This study will determine the effectiveness of mirtazapine in reducing anxiety in children with autistic disorder, Asperger's disorder and Pervasive Developmental Disorder.

Detailed Description
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One of the areas receiving very little attention in Pervasive Developmental Disorders (PDDs) is that of anxiety. Anxiety is common in PDD, but has not yet been fully characterized. The primary objective of this study is to conduct a preliminary placebo-controlled trial of mirtazapine for the treatment of anxiety associated with PDDs. We hypothesize that mirtazapine will be safe and well tolerated.

Official Title
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Mirtazapine Treatment of Anxiety in Children and Adolescents With Pervasive Developmental Disorders

Conditions
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Autism Spectrum Disorders

Intervention / Treatment
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* Drug: Placebo
* Drug: Mirtazapine


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Ages 5-17 years Diagnosis of autistic disorder, Asperger's disorder or Pervasive Developmental Disorder Not Otherwise Specified (PDD NOS) Clinically significant anxiety as evidenced by a Pediatric Anxiety Rating Scale (PARS) score of 10 or greater Abbreviated intelligence quotient (IQ) greater than 50 on the Stanford Binet 5th Ed. Exclusion Criteria: Diagnosis of Rett's disorder or childhood integrative disorder Diagnosis of obsessive-compulsive disorder (OCD), post-traumatic stress disorder, major mood disorder, psychotic disorder, or substance use disorder Presence of any past or present medical conditions that would make treatment with mirtazapine unsafe Use of other antidepressants or benzodiazepines Use of other psychotropic medications which are ineffective, poorly tolerated, or sub-optimal in terms of dose Previous adequate trial of mirtazapine

Ages Eligible for Study
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Minimum Age: 5 Years
Maximum Age: 17 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Mirtazapine<br>The starting dose for subjects is 7.5 mg daily. The maximum daily dose will be 45 mg. | Drug: Mirtazapine<br>* Subjects will receive 7.5 mg daily at the start of the trial. The dose will be increased by 7.5 mg per week for subjects weighing less than 50 kg and up to 15 mg per week for subjects weighing more than 50 kg depending on efficacy and tolerability.<br>* Other names: Remeron;|
| Placebo Comparator: Placebo<br>Subjects randomized to placebo arm will receive capsules identical in size and appearance to those subjects receiving study drug. Placebo capsules contain inactive ingredients. | Drug: Placebo<br>* Subjects randomized to placebo will receive placebo for duration of the study<br>* Other names: Sugar pill;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mean 10-Week Change in Pediatric Anxiety Rating Scale 5-Item Total Score, Double-blind Phase | The Pediatric Anxiety Rating Scale (PARS) is a clinician-rated instrument that assesses anxiety symptoms that are commonly associated with social anxiety, separation anxiety, and generalized anxiety disorders. Scaled score ranges form 0-25 with higher scores indicating more severe anxiety symptoms. Means were estimated using a repeated measures linear regression model with treatment group, study week (in categories), and their interaction as covariates, and assuming a common mean between treatment groups at baseline. Confidence intervals reflect a Bonferroni multiple testing correction accounting for the selection of two primary outcomes. | Weeks Baseline, 2, 4, 6, and 10 | 
| Proportion of Participants Who Responded to Treatment at 10 Weeks According to the Improvement Item of the Clinical Global Impression-Scale (Response Defined as CGI-I=1 or CGI-I=2) | The Clinical Global Impressions Global Improvement (CGI-I) is designed to take into account all factors to arrive at an assessment of response to treatment. The CGI-I scale ranges from 1 to 7 (1=very much improved; 2= much improved; 3=minimally improved; 4=no change; 5=minimally worse; 6=much worse; 7=very much worse), with lower scores indicating improvement (1=very much improved and 2=much improved). In this study the CGI was focused on the target symptom of anxiety. Participants with a CGI-I score of 1 or 2 were classified as responders. The CGI-I was administered biweekly for 6 weeks and again at 10 weeks during the study. The participant who withdrew from the study before 10 weeks was not included in the calculations. | Screen (Visit 1) Baseline (Visit 2) and Endpoint (Week 10) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Autistic Disorder, Asperger's Disorder, Pervasive Developmental Disorder