Double-blind Trial of Buspirone for the Treatment of Anxiety in Youth With Autism Spectrum Disorders

• Reduction in Pediatric Anxiety Rating Scale (PARS) Score [ Time Frame: baseline to 8 weeks ] [ Designated as safety issue: No ]
  Primary outcome measure of efficacy will be assessed by reduction in anxiety symptom severity as measured by change from baseline. Responders are defined as ≥30% reduction in the Pediatric Anxiety Rating Scale (PARS).
• Clinical Global Impression-Anxiety (CGI-Anxiety) Improvement Score [ Time Frame: baseline to 8 weeks ] [ Designated as safety issue: No ]
  Primary outcome measure of efficacy will be assessed by reduction in anxiety symptom severity as measured by Clinical Global Impression-Anxiety (CGI-Anxiety). Responders are defined as a score of ≤2 on the improvement subscale (i.e., "much" or "very much improved").

The main objective of this exploratory 8 week pilot study is to evaluate the safety and efficacy of buspirone for the treatment of anxiety in youth (ages 6-17 years) with autism spectrum disorders. The study results will be used to generate hypotheses for a larger randomized controlled clinical trial with explicit hypotheses and sufficient statistical power.

• Drug: Buspirone
  Children with Autism Spectrum Disorders will receive buspirone or matched placebo. Buspirone will be titrated to the maximum daily dose during the first four weeks of the trial (dose titration phase). Week 4 onwards subjects will be maintained on maximum achieved dose till the end of the trial (dose maintenance phase). During the titration phase total dose of buspirone will be increased at each visit by 5mg and on the 4th day after each visit by 5mg.
  Other Name: Buspar
• Drug: Placebo
  Children with Autism Spectrum Disorders will receive buspirone or matched placebo. Buspirone will be titrated to the maximum daily dose during the first four weeks of the trial (dose titration phase). Week 4 onwards subjects will be maintained on maximum achieved dose till the end of the trial (dose maintenance phase). During the titration phase total dose of buspirone will be increased at each visit by 5mg and on the 4th day after each visit by 5mg.

• Active Comparator: Buspirone
  Intervention: Drug: Buspirone
• Placebo Comparator: Placebo
  Intervention: Drug: Placebo

Inclusion Criteria:

• Male or female participants between 6 and 17 years of age.
• Fulfills diagnosis of autism spectrum disorders by meeting DSM-IV-TR PDD diagnostic criteria of autistic disorder, Asperger's disorder, or PDD-NOS as established by clinical diagnostic interview.
• Participants with a score of ≥60 on the Anxiety/Depression subscale of Child Behavior Checklist (CBCL) and CGI-Anxiety severity of ≥4.
• Subjects can be on psychotropic drugs if they have been on the medication for at least 4 weeks prior to initiating study treatment and if they are on a stable dose.
• Subjects with disruptive behavior disorders, mood, or psychosis will be allowed to participate in the study provided they do not meet any exclusionary criteria.

Exclusion Criteria:

• Mental retardation (I.Q. <70)
• DSM-IV-TR PDD diagnosis of Rett's disorder, and childhood disintegrative disorder.
• History of active seizure disorder (EEG suggestive of seizure activity and/or history of seizure in last 1 month).
• Subjects with a medical condition or treatment that will either jeopardize subject safety or affect the scientific merit of the study, including: pregnant or nursing females, organic brain disorders, uncorrected hypothyroidism or hyperthyroidism, clinically significant abnormalities on ECG (e.g. QT prolongation, arrhythmia), history of renal or hepatic impairment.
• Clinically unstable psychiatric conditions or judged to be at serious suicidal risk.
• History of substance abuse (except nicotine of caffeine) within past 3 months or urine drug screen positive for substances of abuse.
• Any other concomitant medication with primary central nervous system activity other than stable regimens for >2 weeks.
• A non-responder or history of intolerance to buspirone, after treatment at an adequate dose and duration as determined by the clinician.