One of the multisite, double-blind, placebo-controlled trials
that led to the FDA approval of risperidone for the treatment of irritability in children and adolescents with autism revealed a 69% response rate with a 57% decrease in irritability as measured by the ABC Irritability subscale.69 Similar results were observed Inhibitors,research,lifescience,medical in another randomized study of children and adolescents with ASDs.70 Other investigations have also found increased relapse rates upon blinded risperidone discontinuation in children and adolescents with ASDs.71,72 Risperidone treatment coupled with parent management training was also found to reduce irritability, stereotypic behavior, and hyperactivity/noncompliance more effectively than risperidone monotherapy in children with
ASDs, aged 4 to 13 years.73 In controlled studies of risperidone in children with ASDs younger than 5 years, results have been mixed. One study of 24 children, aged 2 to 6 years, found minimally greater Inhibitors,research,lifescience,medical improvement in target symptoms but with insufficient findings to direct treatment.74 Another study from India Inhibitors,research,lifescience,medical in children aged 2 to 9 years revealed a 63% response rate as measured by a 20% or greater improvement from baseline in the Childhood Autism Rating Scale (CARS), with no responders in the placebo group.75 Dosages in the studies above ranged from 0.5 to 3.5 mg/day, with the combination risperid one/parent management training group requiring a lower mean dose compared with the risperidone monotherapy group (1.98 versus 2.26 mg/day, respectively). Adverse effects included increased appetite, weight gain, fatigue, somnolence, drowsiness, dizziness, anxiety, hypersalivation, upper respiratory tract infections, Inhibitors,research,lifescience,medical and Inhibitors,research,lifescience,medical rhinitis. Transient dyskinesias occurred in 15% of the risperidone-treated group from the India study. Risperidone was also EPO906 associated with a 2- to 4-fold mean increase in serum prolactin in children and adolescents with autism, although increases diminished
with time.76 The first study to include adults was Linifanib (ABT-869) an open-label trial of risperidone in 11 individuals with autism, aged 6 to 34 years (mean age, 18 years), which revealed improvements in explosive aggression, SIB, and sleep hygiene.77 A 12-week, double-blind, placebo-controlled trial in 31 adults with ASDs, aged 18 to 44 years (mean age, 28 years), found risperidone superior to placebo in reducing aggression, irritability, repetitive behaviors, anxiety or nervousness, and depression, with a 57% response rate compared with none in the placebo group.78 Longterm efficacy with risperidone in the treatment of irritability was demonstrated in a cohort of individuals with MR and autism, aged 8 to 56 years (mean age, 22 years), revealing a 60% response rate with a 50% decrease in the ABC Irritability subscale score.