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The pharmacokinetics of Risperdal and its weight gaining side effects in adolescents
with irritability due to autism and disruptive behavior disorders
Chelsea M. Vink
Grand Valley State University, Allendale, Michigan 49401
Introduction
Conclusion
Results
Risperidone, known by the brand name of Risperdal, is an
atypical antipsychotic medication often prescribed to
adolescents in psychiatric facilities in order to treat their
irritability and aggression due to autism and disruptive
behavior disorders. One of the side effects associated with
Risperdal is an increase in weight gain. The combination of
a medication with a common side effect of weight gain, in
addition to a sedentary lifestyle due to being in a locked
facility, can lead to serious health concerns associated with
obesity including Type II Diabetes, high blood pressure, and
high cholesterol.
Risperdal works to decrease activity of serotonin and norepinephrine in the deep limbic system, as well as decrease activity of dopamine in the
cingulate gyrus.
Normal brain activity
Objective
ADHD
Disruptive behavior
disorder
“Ring of Fire”
ASD engaging in eye contact
This project was done in order to discover if there’s a better
alternative to Risperdal consistent with the medication’s
positive outcomes but without the negative side effect of
weight gain.
Although Risperdal is associated with significant weight
gain in adolescents, other alternatives that are offered to
reduce agitation and irritability in adolescents with autism
and disruptive behavior disorders seem to be about equal, if
not larger, in the magnitude of weight gained as a side effect
of the medication (Table 2).
Since Risperdal is proven to be effective, adolescents
with autism and behavioral disorders will likely continue to
be prescribed Risperdal for their irritable and aggressive
symptoms. Since weight gain is a significant side effect,
there should be plans implemented for daily activity and
exercise for adolescents that take Risperdal and are patients
in a locked psychiatric facility in order to reduce risk of
serious health concerns associated with obesity such as Type
II Diabetes, high blood pressure, and high cholesterol.
Literature cited
American Psychiatric Association. (2013). Diagnostic and statistical manual of mental disorders: DSM-5. Washington, D.C: American
Psychiatric Association.
Baldessarini, R.J., Gardner, D.M., Waraich, P. (2005). Modern antipsychotic drugs: a clinical overview. Canadian Medical Association
Journal 172(13). 1703-11. Retrieved from PubMed.
The Cochrane Collaboration. (2012). Atypical antipsychotic drugs for disruptive behavior disorders in children and youths. In PubMed
Health. Retrieved from http://www.ncbi.nlm.nih.gov/pubmedhealth/PMH0048481/
Colpaert, F.C. (2003). Discovering risperidone: the LSD model of psychopathology. Nature Reviews. Drug Discovery 2(4). 315-20. Retrieved
from PubMed.
Dietrich, A., Dinnissen, M., Hoekstra, P.J., Van den Hoofdakker, B.J. (2015). Clinical and pharmacokinetic evaluation of risperidone for the
management of autism spectrum disorder. Expert Opinion on Drug Metabolism & Toxicology 11(1), 111-24. Retrieved from PubMed.
Eens, A., Gommeren, W., Janssen, P.A., Leysen, J.E., Stoof, J.C. (1988). Biochemical profile of Risperidone, a new antipsychotic. The
Journal of Pharmacology and Experimental Therapeutics 247(2). 661-70.
Günther, T., Herpertz-Dahlmann, B., Jolles, J., & Konrad, K. (2006). The influence of risperidone on attentional functions in children and
adolescents with attention Deficit/Hyperactivity disorder and co-morbid disruptive behavior disorder. Journal of Child and
Adolescent Psychopharmacology 16(6), 725-735. Retrieved from PsycINFO.
Miral, S., Gencer, O., Neslihan Inal-Emiroglu, F. (2008). Comparison of long-term efficacy and safety of risperidone and haloperidol in
children and adolescents with autistic disorder: an open label maintenance study. European Child and Adolescent Psychiatry 17(4).
217-25. Retrieved from PubMed.
Materials and methods
Electronic searches were performed in PubMed (1998 –
2015), PsycInfo (1993 – 2014), MEDLINE (1993 – 2014),
and WEBMD (2007). The main search strategy used
keywords for medications (risperidone OR atypical
antipsychotics OR medications OR prescriptions OR mood
stabilizers) and mood/mental disorders (aggression OR
irritability OR autism OR disruptive behavior disorders OR
conduct disorder OR oppositional defiant disorder OR
ADHD). In addition, psychiatric illnesses were researched
using the Diagnostic and Statistical Manual of Mental
Disorders (5th ed.: DSM-V; American Psychiatric
Association, 2013). An outline was created and constantly
updated in order to maintain cohesiveness of research.
As demonstrated in the single-photon emission computerized tomography (SPECT) scans above, brain activity of patients with disruptive behavior
disorders, autism, and ADHD tend to show over activation in the deep limbic system and cingulate gyrus.
Table 1. Target Receptors of Medications used to Treat Irritability
Drug
High Affinity
Moderate Affinity
Risperidone
Serotonin: 5-HT2A
Dopamine: D2
Adrenaline: α1, α2
Histamine: H1
Serotonin: 5-HT2A, 5-HT2C, 5HT6
Dopamine: D1, D2, D3, D4
Adrenaline: α1
Histamine: H1
Serotonin: 5-HT1A, 5-HT2
Dopamine: D1, D2
Adrenaline: α1, α2
Histamine: H1
Serotonin: 5-HT1A, 5-HT2A
Dopamine: D2, D3
Serotonin: 5-HT1A, 5-HT1C, 5-HT1D Dopamine: D1
Olanzapine
Quetiapine
Aripiprazole
Figure 1. Molecular
structure of risperidone
Clozapine
Haloperidol
Serotonin: 5-HT2A, 5-HT2C, 5HT6, 5-HT7
Dopamine: D4
Adrenaline: α1A, α2A
Histamine: H1
Muscarinic: M1
Serotonin: 5-HT2
Dopamine: D2
Weak Affinity
Brain SPECT scans
Amen Clinics & Brain SPECT Imaging. (2012). Retrieved from http://brainworldmagazine.com/amenclinics-brain-spect-imaging/
Nuclear Imaging of Brains. (2015). Retrieved from http://bravacorp.com/brainimagesfire.html
Puckette, M. (2009). Defying ODD: What it is, and ways to manage. Retrieved from
http://www.raisingtroubledkids.com/odd-basics/
Spanaugle, M. (2012). Anxiety. Retrieved from http://sponauglewellness.com/wellnessprograms/anxiety/
Spect Scans. (2015). Retrieved from http://www.addcare.com/spect-scans/
Table 2. Average Weight Gain in Adolescents
Serotonin: 5-HT3
Muscarinic: M1, M2, M3, M4, M5
X
Serotonin: 5-HT2C, 5-HT7
Dopamine: D4
Adrenaline: α1
Histamine: H1
Serotonin: 5-HT1A, 5-HT3
Dopamine: D1, D2
X
GABA: GABAA
Adrenaline: β1
X
X
Dopamine: D3, D5
X
Drug
Brand Name Average Weight Gain
Risperidone
Olanzapine
Quetiapine
Aripiprazole
Clozapine
Haloperidol
Risperdal
0 – 4.4 kg
Zyprexa
0.9 – 13.5 kg
Further information
Seroquel
2.3 – 6.1 kg
Abilify
0 – 4.4 kg
Clozaril
0.9 – 9.5 kg
Haldol
0 – 4.4 kg
More information on brain SPECT scanning can be found on
Amen Clinics’ website located at
http://www.amenclinics.com/.
Information on psychiatric illnesses such as ADHD,
ASD, oppositional defiant disorder, and conduct disorder can
be found in the Diagnostic and Statistical Manual of Mental
Disorders (5th ed.: DSM-V; American Psychiatric
Association, 2013).