Buspirone Treatment of Anxiety in Williams Syndrome

Inclusion Criteria:

1. Age 5 to 65 years of age.

2. Diagnosis of WS confirmed via genetic testing or a clinical diagnosis made by aclinician with significant experience treating patients with WS.

3. Clinically significant anxiety as evidenced by a Pediatric Anxiety Rating Scale (PARS) score of 10 or greater (5-item scale). The PARS ("The Pediatric AnxietyRating Scale (PARS): Development and psychometric properties." 2002) was chosen asan inclusion criterion (and outcome measure) since it assesses severity acrosscommon anxiety disorders in children including generalized anxiety, social anxiety,separation anxiety, and transition-associated anxiety. In addition, it is aninstrument that allows the clinician to incorporate both child and parent reportinto a final clinician-rated score for each item.

4. A Clinical Global Impression Severity Item score ≥ 4 (moderate) for anxiety symptomsat Screen and Baseline.

Exclusion Criteria:

1. Diagnosis of OCD, posttraumatic stress disorder, major mood disorder, psychoticdisorder, or substance use disorder. These disorders are exclusionary since theprimary treatment of these disorders may require acute psychosocial treatments orother medications that would confound the assessments.

2. Presence of any past or present conditions that would make treatment with buspironeunsafe. This includes allergy to buspirone, liver or kidney disease, and pregnancy (or being sexually active without using acceptable methods to prevent pregnancy).

3. Use of selective serotonin reuptake inhibitors (SSRIs), serotonin norepinephrinereuptake inhibitors (SNRIs), benzodiazepines, antihistamines (as needed use of anantihistamine for the treatment of allergies will be permitted), or antipsychotics.Subjects will need to be off medications from these classes for at least 5elimination half-lives prior to beginning the trial.

4. Use of other psychotropic medications which are ineffective, poorly tolerated, orsub-optimal in terms of dose. A board-certified child and adolescent psychiatristwill assess any other psychotropic medications being used and determine whether theyare effective, tolerated, and optimal in terms of dose. Concurrent use of apsychotropic medication (other than SSRIs, SNRIs, benzodiazepines, antihistamines,or antipsychotics) will be allowed if the dose has been stable for 30 days and ifthey meet the criteria of effectiveness, tolerability, and dose.

5. Previous adequate trial of buspirone. An adequate trial will be defined as a totaldaily dose of ≥20 mg for at least 4 weeks. In addition, subjects who developedsignificant adverse effects during a trial of buspirone at any dose or duration willbe excluded.

6. Severe or profound intellectual disability based on clinical assessment and reviewof standardized assessment of cognitive skills. Subjects will undergo standardizedtesting and be evaluated by study staff to determine cognitive capabilities.Participants determined to have severe or profound intellectual disability will beexcluded.