study of risperidone in adults - 05/31/2012

Antipsychotic (or neuroleptic) drugs were originally designed to treat schizophrenia, but have been used to address autistic behaviors including severe aggression, self-stimulation, hyperactivity, and social withdrawal.  Use of risperidone and other atypical antipsychotics is fairly common in the treatment of autism, and conventional antipsychotics, like haloperidol, continue to be used less frequently.  Most conventional and atypical antipsychotics are potent dopamine (DA) receptor antagonists, but atypical (second-generation) antipsychotics differ from conventional (first-generation) antipsychotics in that they usually exhibit serotonin receptor antagonism in addition to blocking dopamine receptors.  Conventional antipsychotic use is associated with a high frequency of dyskinesias (involuntary movements and/or diminished efficiency of voluntary movements), so atypical antipsychotics are more frequently prescribed for children with autism.  Atypical antipsychotics include risperidone (Risperdal), olanzapine (Zyprexa), quetiapine (Seroquel), ziprasidone (Geodon),  amisulpride (Solian), and aripiprazole.  

Clozapine (Clozaril) is an atypical antipsychotic that requires frequent blood monitoring because of its potential life-threatening effects on the white blood cell count.  Since many children with autism do not tolerate frequent blood draws, there are few, if any, studies of its effectiveness with autistic children.

Although some doctors may consider antipsychotics to be the most effective medication available for reducing the overall symptoms of autism, their use is limited due to the many and often severe side-effects associated with these drugs.  Side effects may include anxiety, dizziness, drowsiness, headaches, unwanted sedation, stiffness, restlessness, involuntary movements (dyskinesias, with both atypical AND conventional antipsychotics), dysphoria (intense depression), weight gain, diabetes, tooth deterioriation, and seizures. 

Parents should keep a diary before, during, and after antipsychotic use in order to track effectiveness and any side effects.

Title:  A double-blind, placebo-controlled study of risperidone in adults with autistic disorder and other pervasive developmental disorders

BACKGROUND:

Neurobiological research has implicated the dopamine and serotonin systems in the pathogenesis of autism. Open-label reports suggest that the serotonin2A-dopamine D2 antagonist risperidone may be safe and effective in reducing the interfering symptoms of patients with autism.

METHODS:

Thirty-one adults (age [mean+/-SD], 28.1+/-7.3 years) with autistic disorder (n=17) or pervasive developmental disorder not otherwise specified (n=14) participated in a 12-week double-blind, placebo-controlled trial of risperidone. Patients treated with placebo subsequently received a 12-week open-label trial of risperidone.

RESULTS:

For persons completing the study, 8 (57%) of 14 patients treated with risperidone were categorized as responders (daily dose [mean+/-SD], 2.9+/-1.4 mg) compared with none of 16 in the placebo group (P<.002). Risperidone was superior to placebo in reducing repetitive behavior (P<.001), aggression (P<.001), anxiety or nervousness (P<.02), depression (P<.03), irritability (P<.01), and the overall behavioral symptoms of autism (P<.02). Objective, measurable change in social behavior and language did not occur. Nine (60%) of 15 patients who received treatment with open-label risperidone following the double-blind placebo phase responded. Other than mild, transient sedation, risperidone was well tolerated, with no evidence of extrapyramidal effects, cardiac events, or seizures.

CONCLUSION:

Risperidone is more effective than placebo in the short-term treatment of symptoms of autism in adults.