Risperidone

1. Risperidone
as used for autism spectrum disorder

2. Autism Spectrum Disorder (ASD)
• Devastating, highly variable neurodevelopmental disorder
• Affects boys more than girls
• Includes individuals who express impaired social interaction, impaired verbal
and non-verbal communication, and restricted and repetitive behavior.
• Other aspects include atypical eating, lack of social or emotional reciprocity,
repetitive use of language or idiosyncratic language, and persistent
preoccupation with unusual objects.

3. Treatment
• Treatment generally focus primarily on educational interventions along with
behavior modification.
• However, a small list of medications has been shown to improve some of
the behavior symptoms of autism spectrum disorder
• One of these medications is risperidone.

4. Risperidone
• second-generation atypical antipsychotic
• anti-serotonergic, anti-adrenergic and
anti-histaminergic
• effective and well tolerated for the
treatment of tantrums, aggression, or
self-injurious behavior in children with
autistic disorder
• HIGHLY CONTROVERSIAL…WHY?

5. Adverse Effects
• Most common: weight gain due to increased insulin resistance- average child
gains six pounds in first eight weeks
• Gynecomastia caused by increased prolactin levels
• Sleepiness and fatigue
• Hypotension
• Tardive dyskinesia

6. Pharmacokinetics of Risperidone
• Bioavailability is 70%
• Hepatic metabolism by CYP2D6
• Renal excretion
• Peak plasma time in extensive metabolizers is three hours; in poor
metabolizers it can reach 17 hours.

7. Drug Interactions
• •Antidepressants such as paroxetine and fluoxetine
• •Heartburn medications such as ranitidine and cimetidine
• •Anti-seizure drugs, such as carbamazepine, phenobarbital, and phenytoin
(Dilantin)
• •Other medications for mental illness, including clonazepine
• •Certain antibiotics, such as rifampin

8. Risperidone Binding
• Risperidone has high affinity for serotonin type 2 (5-HT2) receptors.
• It binds to dopamine D2 receptors with 20 times lower affinity than that for 5-HT2
receptors.
• antagonizes alpha1-adrenergic, alpha2-adrenergic, and histaminergic receptors
• moderate affinity for serotonin type 1 (5-HT1C, 5-HT1D, 5-HT1A) receptors, and
has weak affinity for dopamine D1 receptors
• no affinity for muscarinic, beta1-adrenergic, and beta2-adrenergic receptors

9. Pharmacogenomics of Riperidone
• HTR2A-1438G allele = poorer clinical outcomes. WHY? These people
exhibit lower availability of the 5-HT2A receptors
• ABCB1 c.1236C>T polymorphism = better clinical outcomes. WHY? These
individuals exhibit higher availability of the 5- HT2A receptors

10. Communication
• Physician, nurse, and pharmacist must work together to communicate risks
and benefits of all medications.
• Risperidone requires close monitoring for adverse effects
• Children with austism spectrum disorder are a vulnerable population

11. References
• Arcangelo, V. P., & Peterson, A. M. (2013). Pharmacotherapeutics for Advanced Practice: A Practical Approach (3rd ed. (pp. 696-714). Ambler, PA:
Lippincott Williams & Wilkins.
• Aman, M., Rettiganti, M., Nagaraja, H. N., Hollway, J. A., McCracken, J., McDougle, C. J., ... & Vitiello, B. (2015). Tolerability, Safety, and Benefits of
Risperidone in Children and Adolescents with Autism: 21-Month Follow-up After 8-Week Placebo-Controlled Trial. Journal of child and adolescent
psychopharmacology, 25(6), 482-493.
• Carbemazepine. Medscape Drugs and Diseases. Retrieved November 11, 2015 from http://reference.medscape.com/drug/tegretol-xr-equetro-
carbamazepine-343005
• Filipek PA, Accardo PJ, Baranek GT, Cook EH, Dawson G, Gordon B, Gravel JS, Johnson CP, Kallen RJ, Levy SE, Minshew NJ, Ozonoff S, Prizant BM,
Rapin I, Rogers SJ, Stone WL, Teplin S, Tuchman RF, Volkmar FR (1999). "The screening and diagnosis of autistic spectrum disorders". J Autism Dev
Disord 29 (6): 439–84.
• LLerena, A., Berecz, R., Peñas-LLedó, E., Süveges, Á., & Fariñas, H. (2013). Pharmacogenetics of clinical response to risperidone. Pharmacogenomics,
14(2), 177-194.
• Risperidone (2015). Medscape Drugs and Diseases. Retrieved November 11, 2015 from http://reference.medscape.com/drug/risperdal-consta-
risperidone-342986#10
• Schatzberg, AF, Nemeroff, C . The American Psychiatric Publishing Textbook of Psychopharmacology. 4th ed.American Psychiatric Publishing, 2009.