1. Risperidone as Treatment for Autism Spectrum Disorders
Sarah Wright
Psychopharmacology
Santa Clara University
March 13, 2015

2. RISPERIDONE AS TREATMENT FOR ASDs 2
Abstract
Risperidone is classified as an atypical antipsychotic drug that was introduced in 1994
and is used to treat Schizophrenia, Bipolar disorder, and irritability in individuals with
autism. It was synthesized in attempt to replicate clozapine effectiveness without its side
effects. Currently it is used in combination with therapy for children and adults with ASDs to
treat symptoms of aggression towards others, deliberate self-harm or injury, temper tantrums,
and changing moods. Risperidone is effective in treating these symptoms due to the
antagonist behavior on dopamine and serotonin. This blockage results in lowering arousal
that children with ASDs may be sensitive to. The drug is typically taken orally or by
intramuscular long-acting injection. The effects peek from about an hour after administration
and the drug is metabolized by the liver enzyme CYP2D6 with a half-life of 3-20 hours
depending on the quality and quantity of the enzyme. There have been numerous studies
done in the past decade on the effectiveness of the drug, most of which conclude that the
majority of children’s aggression decreased while taking it. While risperidone is a very
effective and commonly used treatment in children above the age of three with ASDs, there
are side effects that should be acknowledged, such as anxiety, trouble sleeping, nausea,
severe tiredness, and weight gain. To abstain from these side effects and others that could
occur, Applied Behavior Analysis (ABA) therapy is an extremely common and effective
alternative for children with ASDs. ABA therapy consists of a team of therapists and
clinicians trained in the subject of ASDs and ABA. This team works together and hands on
with the child to gauge the gap between chronological and functional age to determine
activities needed to improve temperament, education, and daily living. Often times,
risperidone is used simultaneously with ABA therapy in order to treat the symptoms of

3. RISPERIDONE AS TREATMENT FOR ASDs 3
aggression in order to allow for effective therapy sessions. Each child diagnosed with an
ASD is different, especially since ASDs are spectrum disorders, meaning the range of
severity is broad. Every treatment with a child with an ASD is individualized whether they
are being treated with risperidone, ABA therapy, or both conjointly. One child with an ASD
may need a very different treatment plan than another, meaning the diagnosis and assessment
of the disorder is imperative.
Keywords: Autism Spectrum Disorders, Applied Behavior Analysis, children, antipsychotic

4. RISPERIDONE AS TREATMENT FOR ASDs 4
Introduction
Autism Spectrum Disorders is a growing concern in the world today, classified as a range
of complex neurodevelopment disorders consisting of severe impairment in several areas of
development, including deficits in social interactions, communication, and presence of
stereotyped behavior and activities (6). The diagnosis of ASDs has been increasing, now up to
about 1% of all children diagnosed with an ASD (pg520). The cause of this increase is unknown,
whether it is due to increased knowledge of the symptoms, or actual increase in the disorder
prevalence. From what has been observed, ASDs occurs in all ethnic, socioeconomic and age
group, however males are four times more likely to have the disorder than females (6).
The term autism was first used in 1908 by psychiatrist Eugen Bleuler when he was
attempting to describe patients with Schizophrenia (5). In 1943 and 1944, both Leo Kanner and
Hans Asperger studied groups of children and found similar observations in the developmental
deficits and sensitivity to certain stimuli. Bruno Bettelheim then studied different therapy
sessions with children he claimed were autistic, resulting in his conclusion that the symptoms
stemmed from “coldness of their mothers” (5). This theory was later refuted in 1964 by
psychologist and father of a child with autism, Bernard Rimland, who claimed autism was due to
neural implications. In the 1980s, research and studies on autism and the disorder became better
understood as a neurological and possibly genetic disorder.
Recently, studies have found irregularities in several regions of the brain in people with
an ASD, while other studies suggest abnormal levels of serotonin and other neurotransmitters are
present in the brain of people with the disorder (6). There still, however, is no cause and effect
relationship for the onset of ASDs. Ole Ivar Lovaas continued research on autism and behavior
analysis to develop treatment therapies like ABA therapy. In the past, antidepressants (SSRIs)

5. RISPERIDONE AS TREATMENT FOR ASDs 5
were used to treat symptoms of ASDs, but then the efficacy of risperidone was discovered. It is
now known that atypical antipsychotics like risperidone are clinically the most effective in
reducing aggression, irritability, and tantrums in children with ASDs (520).
While there are drugs to help reduce symptoms that come with ASDs, there is no actual
treatment or any medications that cure the disorder. Most drugs used in response to ASDs reduce
aggression, anxiety, repetitive behaviors, mood changes, hyperactivity, impulsiveness, and
maladaptive behavior through targeting the neurochemical systems involved with the
pathophysiology of ASDs (520). There are currently two FDA approved: risperidone and
aripiprazole.
Risperidone is the second classified atypical antipsychotic drug that was introduced in
1994 and is used to treat Schizophrenia, Bipolar disorder, and irritability in individuals with
Autism. It was synthesized in attempt to replicate clozapine effectiveness without its side effects
and with low risk of extrapyramidal symptoms (EPS) (520). It is a second-generation
antipsychotic (SGA). Currently it is used in combination with therapy for children between the
ages 5 and 16 years of age with an ASD to treat symptoms of aggression towards others,
deliberate self-harm or injury, temper tantrums, and changing moods (4)(7)(8). Risperidone was
one the first FDA approved drug for symptomatic treatment for irritability in children and
adolescents with ASDs on October 6, 2006 (7).
Prompt: Mechanism of action - What's known about the drug you selected for your paper? How
is the drug administered? How move about the body? What's known about the drug you
selectedfor your paper? How is the drug administered? How move about the body? What
does the drug do at the synapse? Where in the nervous systemdoes it have it's effect (main
and side effects)? What do you know about the neurotranmitter(s) the drug effects (nuclei,
projections, behavior)? Cite sources. Refer to your diagram and include it in your paper,
either imbedded in the text or as Figure 1 at the end of the paper.

6. RISPERIDONE AS TREATMENT FOR ASDs 6
Risperidone is administered either orally or through long-acting intramuscular injection.
Dosing is individualized according to the response and tolerability of each individual child.
Rapid absorption occurs after oral administration, peeking within an hour and food having no
effect on absorption. It then binds to plasma proteins to be distributed throughout the body. It is
metabolized in the liver by the enzyme CYP2D6 down to 9-hydroxyrisperidone, which has a
similar pharmacological activity as risperidone. The metabolic half-life for individuals with
extensive metabolizers is about 3 hours and for poor metabolizers about 20 hours (520). The
three hour metabolic half-life means the drugs is active for about 23 hours, so the medication is
taken typically once a day. The long-acting injection is encapsulated in biodegradable polymer
microspheres suspended in a water-based solution that lasts up to two weeks (520).
Other medications that have been researched or used in treatment of symptoms in individuals
with ASDs include traditional anti-ADHD medications like methylphenidate, atomoxetine,
guanfacine, and clonidine (520). These drugs have shown modest efficacy in response to
treatment of hyperactivity, impulsiveness, and attention deficit in ASDs, however the side effects
limit the use. There is still research being done on other medications, one being a diuretic and
chloride channel antagonist called bumetanide, which seems promising in effectiveness so far
(520). Another possible treatment involves omega-3 fatty acid combined with parent training and
supplementary therapy, but there have been contradictory findings on whether it is effective
(520).
Prompt: What does the drug do at the synapse? Where in the nervous systemdoes it have
it's effect (main and side effects)? What do you know about the neurotranmitter(s) the drug
effects (nuclei, projections, behavior)?
Risperidone is a dopamine and serotonin antagonist at D2 and 5-HT2, along with Alpha
1, Alpha 2, and H1, receptors which results in improved control of psychotic symptoms with a

7. RISPERIDONE AS TREATMENT FOR ASDs 7
minimum of neuroleptic-induced EPS at low doses of 6 milligrams (520). Risperidone has higher
affinity for 5-HT2A receptors than for D2 receptors (520) (3). This means that the drug, along
with other antipsychotics, reduce dopaminergic neurotransmission. It also raises the level of the
hormone prolactin (10), which could be terms for concern in the long run. The drug interacts
with other receptors and neurotransmitter systems very little or not at all, including cholinergic
receptors.
Dopamine neurotransmitters are categorized as a chatecholamine transmitter located in
the central nervous system, specifically in the hypothalamus, the nigrostriatal pathway involving
the substantia nigra, basal ganglia, and the cell bodies of the brain stem and tegmentum, effecting
the cerebral cortex, as well as the forebrain limbic system (21). These circuits involving blockade
of dopamine receptors have implications of regulating hormones (hypothalamus), regulating
movement (substantia nigra and basal ganglia), and other dopaminergic functions like pleasure
(21). D2 receptors are the primary receptors responsible for behavioral states, which is the main
effect risperidone has on the brain. While the antagonist action against D2 receptors is helpful in
treating behavioral symptoms that come with ASDs and other conditions, high levels of
dopamine blockade can lead to parkinsonian symptoms, or what is typically referred to as EPS
(extrapyramidal symptoms) (338). Dopamine is also related to possible long term implications of
tardive dyskinesia (339). While this is true for many antipsychotics, risperidone and other
second-generation antipsychotics (SGAs) are said to have little or no implications of EPS or TD
(339).
Risperidone also antagonizes serotonin receptors (5HT2), which was first researched in
relation to LSD in the 1950s. Serotonin is prevalent in the upper brain stem, specifically the pons
and the medulla which have implications on transferring information to the rest of the brain (22).

8. RISPERIDONE AS TREATMENT FOR ASDs 8
Serotonin receptors are involved in impulsivity, which is the main role the blockade of 5HT2
receptors play in the treatment of ASDs (133).
Prompt: Acute and long term effects of use of the drug. Are there concerns?
Some serous adverse effects are high body temperature, drug-induced tardive dystonia,
excessive thirst, hyperglycemia, including ketoacidosis or hyperosmolar coma, hypothermia,
mania, neuroleptic malignant syndrome, priapism, seizure, syncope, tardive dyskinesia,
thrombocytopenic purpura (***). There are also possible side effects like itching or hives,
swelling in your face or hands, swelling or tingling in your mouth or throat, chest tightness,
trouble breathing, change in urination, constant uncontrollable muscle movement (often in your
lips, tongue, arms, or legs), dry mouth, increased thirst, muscle cramps, and fast, slow, irregular
(uneven), or pounding heartbeat. There also may be a fever, sweating, confusion, muscle
stiffness, lightheadedness, fainting, seizures and numbness or weakness in your arm or leg, or on
one side of your body, sudden or severe headache, and problems with vision, speech, or walking
(4). It is currently unknown if it crosses the placenta or if it is a teratogen. Acute side effects
include anxiety, trouble sleeping, increased dreaming, constipation, diarrhea, nausea, upset
stomach, darkening of your skin, drooling, stuffy nose, heavy bleeding during menstrual period,
severe tiredness, trouble having sex, weight gain (4)(10)(7). There are also other known
interactions like decreasing the action of L-dopa and interacting with carbamazepine and
clozapine, as well as possibly strengthening the action of, or be strengthened by, SSRI
antidepressants (10).
Prompt: Alternative treatment to pharmacotherapy - give one viable option to medication for
treatment. How might this help?
Aside from the pharmacological use of risperidone for Autism Spectrum Disorders, is the
applied behavioral analysis. There are many different therapy companies that use this method of

9. RISPERIDONE AS TREATMENT FOR ASDs 9
treatment, which focuses solely on behavior, which constitute as measurable physical and verbal
actions and skills. It is a scientific approach to understanding behavior and how the environment
surrounding the subject influences the behavior. Therapists have used this method since the
1960’s to help children with autism and other developmental disorders (3).
The main aspect of ABA therapy is how people, specifically children in this case, learn.
Positive reinforcement is a tactic used and studied in ABA in order to increase the likelihood of
desired behaviors. While there are many different methods used in ABA depending on the child,
the setting, and the situation, it is typically used in a small group or one on one setting that is
structured time devoted to ABA therapy. The therapist, commonly referred to as the behavior
analyst or behavior interventionist, will usually have structured activities and instructions for the
child, and the outcome of these activities and instructions (the behavior) is then recorded for
data. Tracking behavior in this systematic manner allows for an overview on the deficits and
development of the child.
The overall goal is not to treat autism, but to make living with it easier and to bridge the
gap between chronological and functional age. While drugs like risperidone work to limit the
stimulation to reduce certain behaviors, ABA therapy works to alter behavior and enhance skill
sets and education (2). While ABA therapy is extremely helpful for children with autism, it is
difficult in terms of time and process. Typically, children remain in an ABA therapy program
from a few months to a few years. These sessions are between an hour and five hours long, two
to five times a week. The process can be exhausting for the child, parents, siblings, and therapist.
There must be a good relationship between the therapist and the family, which is sometimes a hit
or miss. While ABA therapy is a scientifically supported treatment for autism, it is certainly not
as black and white as taking a medication.

10. RISPERIDONE AS TREATMENT FOR ASDs 10
Even with the extensive amount of time and effort that it takes to do ABA therapy with a
child, the treatment is incomparable in terms of benefits. ABA therapy is widely and increasingly
used across the country and is endorsed by a number of state and federal agencies, including the
U.S. Surgeon General, The Centers for Disease Control and Prevention (and The National
Institutes of Health (1). The success rate of significant improvement in children treated early is
80%-90% and 50% of children will begin showing appropriate (chronological) skills and
intelligence (1).
ABA therapy helps not only the child reach their full potential, but teaches the family to
best help the child and use ABA in their own daily life. ABA therapy teaches personal hygiene,
social skills, communication skills, structural and procedural skills for daily life, and overall
education. While teaching these children, their behaviors are studied and positive reinforcement
is set in place to encourage the wanted behavior. The combination of both risperidone and ABA
therapy is typically the overall treatment for children with severe autism so that the child is
controlled enough to work through the therapies to learn and grow (2)
Conclusion: What do you think is the better therapy and why?
In terms of concluding the effectiveness of the risperidone versus applied behavior
analysis therapy, there is difficulty in choosing one over the other. Risperidone is helpful in
calming symptoms of ASDs, while ABA therapy increases ability and lowers deficits in
development. The combination of the two seems most beneficial to a child with an ASD,
specifically those on the more severe side of the spectrum. To conduct ABA therapy, it is most
effective if the child is able to participate fully and better control their impulses and aggression.
Risperidone helps children who struggle with these symptoms so that they can more easily
participate in the therapy session without outbursts, allowing for more productive therapy time.

11. RISPERIDONE AS TREATMENT FOR ASDs 11
Since there are obvious side effects, both acute and long-term, risperidone should only be
prescribed if the symptoms are severely implicating the child’s daily life and therapy sessions.
ASDs are typically treated more so for the developmental deficits in a child rather than
neurological symptoms. Often ABA therapy alone can teach the child to control their behavior
through specific activities and social targets, which is why risperidone is for more intense cases
of ASDs. Risperidone is not necessarily effective on its own due to its lack of influence on social
interactions and communication. ABA therapy is the only clinically effective way to treat these
deficits that come with most ASDs. If the symptoms of impulsivity and aggression are under
control and do not immensely effect the safety and well being of the child and those around
them, solely ABA therapy is most likely sufficient in treating a child with an ASD.
VII. References. Include our text and at least three scholarly publications. Use proper APA
format for your citations both in your paper and in the reference section.
Works Cited
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3Applied Behavior Analysis (ABA). (n.d.). Retrieved February 8, 2015, from
http://www.autismspeaks.org/what-autism/treatment/applied-behavior-analysis-aba
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Psychopharmacology. 4th ed.American Psychiatric Publishing, 2009.

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