a review of pharmacotherapy for autism treatment by: bridget spanarkel

A Review of Pharmacotherapy

for Autism Treatment

by: Bridget Spanarkel

SourcesBooks

Hollander, E. (2003). Autism Spectrum Disorders. New York, NY: Marcel Dekker, Inc.

Jacobson, J.W., Foxx, R.M., & Mulick, J.A. (2005). Controversial therapies for developmental disabilities: Fad, fashion, and science in professional practice. New York, NY: Routledge.

Volkmar, F.R. & Wiesner, L.A. (2009). A Practical Guide to Autism: What Every Parent, Family Member, and Teacher Needs to Know. Hoboken, NJ: John Wiley & Sons, Inc.

Websites United States Food and Drug Administration

Google

Sources PsycINFO

Search: Subject field: “autis*” Any field: “pharmacotherapy”, “medication”, “psychotropic”,

“antipsychotic”, “antidepressant” psychopharmacological”, and/or “drugs”

Search: Subject field: “autis*” Any field: “pharmacotherapy”, “medication” and/or “applied

behavior analysis”, “behavior therapy” 22 results

5 articles using applied behavior analysis alone 3 articles using pharmacotherapy alone 4 reviews of autism in general 3 articles recommending multidimensional treatment plans 3 articles including both ABA and pharmacotherapy 4 other

What is Pharmacotherapy?

Definition: the use of medications or drug therapy for the purpose of preventing and/or treating a disease, disorder, or illness

Also known as: Pharmacologic Treatment, Psychopharmacology, Psychopharmacological Management, Medical Intervention, and Drug Therapy

Antonacci, D.J., Manuel, C., & Davis, E. (2008). Diagnosis and treatment of aggression in individuals with developmental disabilities. Psychiatric Quarterly, 79, 225-247.

Statistics Approximately 56% of children with ASD are

prescribed at least one psychoactive medication per year, and 20% of those children use three or more concurrent psychoactive medications (national Medicaid data in 2001)

Approximately 70% of children diagnosed with ASD between the ages of 8-21 years receive at least one psychoactive medication annually (national insurance company data in 2002)

Antonacci, D.J., Manuel, C., & Davis, E. (2008). Diagnosis and treatment of aggression in individuals with developmental disabilities. Psychiatric Quarterly, 79, 225-247.

Self, T.L., Hale, L.S., & Crumrine, D. (2010). Pharmacotherapy and children with autism spectrum disorder: A tutorial for speech-language pathologists. Language, Speech, and Hearing Services in Schools, 41, 367-375.

History of Pharmacotherapy 1954: first psychotropic medication

was introducedThorazine (antipsychotic)

1960 - 1970s: several studies published using antipsychotic medications for autism

Matson, J.L. & Dempsey, T. (2008). Autism spectrum disorders: Pharmacotherapy for challenging behaviors. Journal of Developmental and Physical Disabilities, 20, 175-191.

Posey, D.J., Stigler, K.A., Erickson, C.A., & McDougle, C.J. (2008). Antipsychotics in the treatment of autism. The Journal of Clinical Investigation, 118, 6-14.


History of Pharmacotherapy Food and Drug Administration (FDA): “Off-label”

Central nervous system stimulants, antipsychotics, anticonvulsant mood stabilizers, selective serotonin reuptake inhibitors (SSRIs), benzodiazepines, and more

2006: first drug FDA approved specifically for autism Risperidone (Risperdal) – antipsychotic medication to

treat irritability associated with autistic disorder, including symptoms of aggression, self-injury, tempter tantrums, and quick changes in mood in adolescents aged 5 to 16 years old. United States Food and Drug Administration (n.d.) FDA approves risperdal for treatment of irritability

associated with autistic disorder. Retrieved from http://www.fda.gov/Drugs/ScienceResearch/ResearchAreas/Pharmacogenetics/ucm237637.html.



Comorbidity Comorbidity: being diagnosed with more

than one disorder at a time Differences in opinion worldwide about

comorbidity and autism For example, should a child with autism also be

diagnosed with an anxiety disorder, or is anxiety simply an associated symptom/behavior of the autism diagnosis?

Specific medications have been developed to target symptoms of major depression, ADHD, bipolar disorder, and anxiety conditions, all of which may occur in persons with autism.

Great area for future research!Matson, J.L. & Dempsey, T. (2008). Autism spectrum disorders: Pharmacotherapy for challenging behaviors. Journal of Developmental and Physical Disabilities, 20, 175-191.


Core Deficits and Associated

Behaviors of Autism

West, L., Waldrop, J., & Brunssen, S. (2009). Pharmacologic treatment for the core deficits and associated symptoms of autism in children. Journal of Pediatric Health Care, 23, 75-89.

Discussion Questions Do you feel psychotropic

medications such as antipsychotics should be prescribed “off-label” to children and adults with autism? Is this ethical?

What are your thoughts on comorbidity in individuals with autism? Should symptoms such as impulsiveness, anxiety, irritability, and mood changes be considered separate disorders or be considered associated behaviors of the autism diagnosis?

Types of Medication

Antipsychotics (Typical and Atypical) Stimulants Antidepressants & Selective

Serotonin Reuptake Inhibitors (SSRIs) Mood Stabilizers & Anticonvulsants Anti-anxiety and Benzodiazepines Sleep Medications

Antipsychotics Also known as: major tranquilizers Some of the first psychiatric medications

developed Typical (first-generation or conventional)

and Atypical (second-generation) Block the effects of dopamine

neurotransmitters in the brain

Findling, R.L. (2005). Pharmacologic treatment of behavioral symptoms in autism and pervasive developmental disorders. Journal of Clinical Psychiatry, 66, 26-31.



Typical Antipsychotics Claim to:

Decrease irritability, aggression, hyperactivity, and tantrums

Decrease self-injurious behavior, motor tics, inattention, and mania

Due to serious side effects, clinicians and researchers have shifted their focus to atypical antipsychotic medications.


Handen, B.L. & Lubetsky, M. (2005). Pharmacotherapy in autism and related disorders. School Psychology Quarterly, 20, 155-171.

Erickson, C.A., Posey, D.J., Stigler, K.A., & McDougle, C.J. (2007). Pharmacotherapy of autism and related disorders, Psychiatric Analysis, 37, 490- 500.

Typical Antipsychotics Generic Name

Haloperidol Thiothixene Chlopromazine

Brand Name Haldol Navane Thorazine




Atypical Antipsychotics Claim to:

Decrease self-injurious behavior, aggression, and stereotyped behavior

Decrease agitation, impulsivity, high activity levels, and temper tantrums

Increase motivation and decrease social withdrawal

Greatly reduced risk of side effects Tardive dyskinesia: motor/movement disorder




Atypical Antipsychotics Generic Name

Risperidone Clozapine Quetiapine Olanzapine Ziprasidone Aripiprazole

Brand Name Risperdal Clozapine Seroquel Zyprexa Geodon Abilify

Chez, M.G., Memon, S., & Hung, P.C. (2004). Neurologic treatment strategies in autism: An overview of medical intervention strategies. Seminars in Pediatric Nursing, 11, 229-235.



Stimulants Medications widely used for treating

problems with attention and hyperactivityAttention Deficit Hyperactivity Disorder

(ADHD) Increase levels of dopamine in the brain Different types

Longer lasting effectsDifferent side effects




Stimulants

Claim to: Increase focus and attentionDecrease restlessness, hyperactivity,

and impulsivity



Stimulants Brand Name

Ritalin Dexedrine Adderall Strattera

Generic Name Methyphenidate Dextroamphetamin

e Amphetamine Atomoxetine



Antidepressants and SSRIs Originally developed for the treatment of

depression or obsessive-compulsive disorder (OCD) Four types of antidepressants

Monoamine oxidase (MAO) inhibitors Tricyclic antidepressants (TCAs) Selective serotonin reuptake inhibitors (SSRIs) “Other agents”

SSRIs are most commonly used with autism Different brain chemicals involved in each

SSRIs: prevent (inhibit) the reabsorption (reuptake) of serotonin after it is produced in the brain, thereby increasing levels of serotonin in the brain



Antidepressants and SSRIs

Claim to:Treat behavioral rigidity, ritualistic

behaviors, and ritualsMay help decrease self-injurious

behaviors and compulsive behaviors



Antidepressants and SSRIs

Generic Name Clomipramine Fluoxetine Citalopram Sertraline Venlafaxine Bupropion Mirtazaphine

Brand Name Anafranil Prozac Celexa Zoloft Effexor Wellbutrin Remeron


Mood Stabilizers & Anticonvulsants

Originally developed to treat mood disorders such as bipolar disorder or mania

Anticonvulsants are commonly used to treat seizure disorders

Some researchers believe that mood disorders may be increased in children with PDDs, as indicated by irritability, over-activity, and aggressive behaviors.

These types of medications are usually only used for autism if the child has an additional diagnosis of a mood disorder, or display cyclical patterns of insomnia and over activity.




Claim to:Decrease mood swings, irritability, over

activity, impulsivity and aggressive behaviors

Decrease self-injury, depression (lithium only), and disruptive behaviors




Generic Name Divalproex Valproic acid Carbamazepine Oxcarbamazepine Lithium compounds

Brand Name Depakote Depakene Tegretol Trilepta Eskalith, Lithone,

Lithobid


Anti-anxiety Medications

Limited research for these types of medication specifically for autism

Three types sometimes used as treatment for autismBenzodiazepinesBeta blockersOpiate blockers


Anti-anxiety Medications

Claim to:Decrease anxiety and stressDecrease irritability and agitation


Anti-anxiety Medications Generic Name

Lorazepam (benz.) Clonazepam (benz.) Propranolol (beta

bl.) Nadolol (beta bl.)

Brand Name Ativan Klonopin Inderal Corgard


Video: “Medicating my Son with

Autism: Why and When its OK”

http://www.youtube.com/watch?v=Zmh7BhM49OA

Side Effects of Pharmacotherapy

All medications have the potential for adverse effects.

Side effect reactions can be neurological, behavioral, cognitive, or physiological.

Severity of side effects Duration of side effects Rate of side effect development Many of the neurological, cognitive, and

behavioral side effects mimic symptoms of autism itself.



Side Effects of Antipsychotics

Second-Generation antipsychotics have significantly less side effects than first-generation antipsychotics


•Tardive dyskinesia•Movement problems•Sedation•Weight gain (Risperidone, Olanzapine)•Possible diabetes•Reducing white blood count (Clozapine)•Fatigue/Drowsiness

•Drooling•Restlessness or akathisia•Allergic reactions (breathing problems, hives, etc.)•Dry mouth•Constipation•Seizures•Malignant hyperthermia

Side Effects of Stimulants Irritability Occasional worsening of hyperactivity Sleep problems Decreased appetites Dizziness Moodiness/agitation Tics Habit problems like skin picking Hallucinations


Side Effects of Antidepressants

Agitation Hyperactivity Insomnia Elated affect Decreased appetite Impulsivity/restlessness Withdrawal effects such as vomiting, nausea,

headaches, abdominal pain Highly sensitive to drug interaction



Side Effects of Mood Stabilizers

Sedation Changes in blood count Liver toxicity Hyperactivity/Insomnia Weight gain Abdominal pain/upset stomach Hyperthyroidism and kidney problems (Lithium) Tremors Polydipsia-- extreme thirst (Lithium) Polyuria-- excessive urination (Lithium) Severe acne (Lithium) Muscle weakness Hemorrhagic pancreatitis (Valproic acid)



Side Effects of Anti-anxiety Medications

Paradoxical agitation Low blood pressure Heart rate problems Sedation Dizziness Nausea Vomiting


Video: “Drugging Our Children”

http://www.youtube.com/watch?v=MR4EWSbXLWA

Discussion Question

After hearing both the claims and side effects, what are your opinions on the use of pharmacotherapy as a treatment for autism?

Interview with Dr. Gina Del Giudice

Mother and Medical Doctor Andrew, 19, is diagnosed

with autism Has been prescribed

various medications, such as mood stabilizers, anti-anxiety medications, and sleeping medications

Also has attended a private school for autism based on applied behavior analysis since he was 3 years old

Dr. Del Giudice has given permission for Andrew’s name and photo to be used in this presentation.

As a doctor, what are your feelings on the use of medications/pharmacotherapy as a treatment for autism? What are the pros and cons? “Medications should be used primarily as a means of targeting and

controlling certain behavioral symptoms so that learning can occur in an individual more easily. This is usually done most effectively when the individual displays symptoms of an additional diagnosis, such as bipolar or an anxiety disorder, because medications have been approved by the FDA specifically for these symptoms. The pros of using medications would be that, when prescribed and monitored correctly, medications can decrease the maladaptive symptoms of autism so that the individual can be more capable of learning and assimilating into society. Some of the cons would be that medications need to be monitored on a consistent basis, which can require frequent visits to the doctor and/or blood tests. Also, many people are not aware of the long term side effects of many psychotropic medications, such as thyroid or heart problems, weight gain, diabetes, or high cholesterol.”

Does thinking about the use of pharmacotherapy from a mother’s perspective change your opinion at all? If so, how? “It’s funny, because when I was going through medical school, I

had no problem reading about all of the side effects that go along with medications on the market today. It was just factual information to be aware of for my future patients. Years later when Andrew was diagnosed with autism, I revisited this same information. Everything became much scarier and much more real. The first time I read about some of the medications that were options for Andrew, I had to put the books away. But now, after seeing the relief that some of these medications has brought him, I know that they do have a role in the treatment of autism, so long as they are prescribed and monitored appropriately.”

Do you think ABA is an effective treatment for autism? “In my opinion, ABA is the only treatment that works for

autism. In some cases, treatments like speech therapy, OT/PT, and medications can be helpful as add-on’s, but the bottom line for me has been simple: the only way Andrew has been able to learn has been through ABA techniques.”

What do you think society’s opinion is on the use of medications as a treatment for children with autism? How does this differ from your opinion as a medical professional? How does this differ from your opinion as a mother? “I think that, generally speaking, people in society have negative feelings

towards the use of medications as a treatment for autism, mainly because it can be very confusing and difficult to understand how and why these medications work. In addition, the side effects that can accompany these medications can be frightening and may seem too cruel to be worth the risk. However, there are also a handful of people in society, especially those who are affected by autism firsthand, who might find themselves feeling desperate to help their children in any way they can, even if that means trying pharmacotherapy as a treatment.

As a medical professional, I believe that medications can be a very safe and often times effective treatment for specific symptoms of autism, so long as they are prescribed and monitored correctly.

As a mother, there isn’t a day that goes by that I do not worry about Andrew’s health, especially when I think about the side effects of the medications he is on. I am disappointed and sad that he needs to be on medications, and worry about the negative connotations attached to these medications. However, I know that Andrew is in good hands, from both a medical and family perspective, and have seen a tremendous difference in his ability to learn and interact with others, once his anxiety was lessened by these medications. These medications have reduced some of his more problematic symptoms enough that the foundation of his learning, ABA, can work, and at the end of the day, knowing that Andrew is learning is one of the most important things to me.”

What does the evidence say?

Evidence Overall, there is partial scientifically validated

evidence supporting the effectiveness of pharmacotherapy as a treatment for autism. Medication – Placebo studies Flawed Methodologies Core deficits versus associated behavioral

symptoms? Very few studies comparing pharmacotherapy and

applied behavior analysis


Canitano, R. & Scandurra, V. (2011). Psychopharmacology in autism: An update. Progress in Neuro-Psychopharmacology and Biological Psychiatry, 35, 18-28.

Evidence: Antipsychotics Overall, typical and atypical antipsychotic

medications have shown some efficacy in the treatment of autism. Typical agents, e.g. Haloperidol – effective in

treating aggression, but adverse effects are unacceptable

Atypical agents, e.g. Risperidone – demonstrated more favorable results in treating irritability, aggression, and self-injury than other similar antipsychotic medications


Evidence: Antidepressants

Very few placebo-controlled, double-blind studies supporting the use of antidepressants or SSRIs for autism treatments.

Overall, there is moderate support for antidepressants and SSRIs (fluvoxamine, fluoxetine, escitalopram) effectively treating symptoms of autism, but adverse effects are intolerable.


Evidence: Stimulants

Very few studies of stimulant medications in children with autism. Methylphenidate (Ritalin) – more effective than placebo

control groups, but only about 50% of subjects showed improvement.

This positive response rate is much lower than the positive response rate of subjects who had ADHD (and not autism) diagnoses

Overall, research tends to show that stimulant medications are less effective in treating symptoms of autism when compared to similar symptoms in typically developing peers


Evidence: Mood Stabilizers

Overall, research has shown that children with autism do not show a positive response to mood stabilizers. However, these medications may be helpful if the child

has symptoms suggesting comorbidity, such as an additional diagnosis of bipolar disorder or another mood disorder

A few reports of case studies in which mood stabilizers and anticonvulsants were effective in decreasing impulsivity and aggression, but these were not of high experimental quality.

Need more research!

Volkmar, F.R. & Wiesner, L.A. (2009). A Practical Guide to Autism: What Every Parent, Family Member, andTeacher Needs to Know. Hoboken, NJ: John Wiley & Sons, Inc.

Evidence: Anti-anxiety Medications

Very little research Benzodiazepines: very little research

conducted with children as subjects, and even less with children with autism specifically

Beta blockers and opium blockers: a few open-label studies and case studies, but good double-blind controlled studies are not yet available

Need more research!

Evidence

Matson, J.L. & Dempsey, T. (2008). Autism spectrum disorders: Pharmacotherapy for challenging behaviors. Journal of Developmental and Physical Disabilities, 20, 175-191. Provided a data based review of existing trends

in the treatment of pharmacotherapy for persons with autism

Quantified the level of research support available for various pharmacological medications on the market today

Trends in the Data


Methodology Concerns because the methods used in the experimental

designs are not adequate enough to make reliable or valid conclusions about the drugs being tested

“Double-blind, placebo-controlled studies” versus “Open-label studies”

Such publications can give the false impression that the medication has been partially validated, when in fact the data are suspect. Very few subjects No control groups Poor reliability and validity measures Rating Scales and Diagnostic Instruments may not be

accurate/reliable Reporting biases



Evidence Identified 14 different

drugs with published studies to treat challenging behaviors and core symptoms of autism


Additional Concerns with the Evidence

Short length of studies Difficult to use animal models for

experimentation Lack of research about the effectiveness of

combined treatments – pharmacotherapy AND behavioral intervention

Intolerable costs of adverse side effects



Why is Pharmacotherapy Used?

Only partial support for the effectiveness of pharmacotherapy for autism!

Inconsistent findings in research Often times, symptoms subside relatively

quickly Requires less intensive staffing/training than

behavioral interventions Pharmacotherapy can be easily administered

outside of facilities with trained staffAntonacci, D.J., Manuel, C., & Davis, E. (2008). Diagnosis and treatment of aggression in individuals with developmental disabilities. Psychiatric Quarterly, 79, 225-247.


Discussion Questions

Do you think pharmacotherapy could be considered an “effective” treatment for autism if it does not directly affect any of the disorder’s core symptoms?

In other words, medications have been shown to target the behavioral symptoms associated with autism, but research has not been able to consistently show improvements in the core deficits of communication, social interaction, and stereotyped behaviors/interests.

Can this still be considered an effective treatment for autism?

Conclusion

Most researchers agree that behavioral treatments remain the primary treatment method for ASD

Pharmacotherapy should only be used to treat the most severe or challenging symptoms of autism that prevent the individual from successfully completing behavioral therapies

Hollander, E., Phillips, A.T., & Yeh, C. (2003). Targeted treatments for symptom domains in child and adolescent autism. The Lancet, 362, 732-734.

Matson, J.L. & Hess, J.A. (2010). Psychotropic drug efficacy and side effects for persons with autism spectrum disorders. Research in Autism Spectrum Disorders, 5, 230-236.


Conclusion Pharmacotherapy, then, should be used as an

adjunctive treatment when behavioral interventions are not fully effective Consider:

Definition of “ineffective” Age of participant Safety of patient, family, and others Patient’s psychological distress Symptoms that jeopardize sustained educational progress

In these extreme cases, it may not be a matter of selecting medication or behavior therapy. Rather, it may be more useful to combine the two interventions.

Matson, J.L. & Hess, J.A. (2010). Psychotropic drug efficacy and side effects for persons with autism spectrum disorders. Research in Autism Spectrum Disorders, 5, 230-236.

Scahill, L. (2008). How do I decide whether or not to use medication for my child with autism? Should I try behavior therapy first?. Journal of Autism and Developmental Disorders, 38, 1197-1198.

Additional Research Needed

Controlled, experimentally sound research on the effectiveness of pharmacotherapy

Additional studies to determine whether behavioral interventions or pharmacotherapy is more effective overall

Studies to determine the effectiveness of medications when used in combination with behavioral intervention

References

Antonacci, D.J., Manuel, C., & Davis, E. (2008). Diagnosis and treatment of aggression in individuals with developmental disabilities. Psychiatric Quarterly, 79, 225-247. Canitano, R. & Scandurra, V. (2011). Psychopharmacology in autism: An update. Progress in Neuro- Psychopharmacology and Biological Psychiatry, 35, 18-28.Chez, M.G., Memon, S., & Hung, P.C. (2004). Neurologic treatment strategies in autism: An overview of medical intervention strategies. Seminars in Pediatric Nursing, 11, 229-235.Erickson, C.A., Posey, D.J., Stigler, K.A., & McDougle, C.J. (2007). Pharmacotherapy of autism and related disorders, Psychiatric Analysis, 37, 490- 500.Findling, R.L. (2005). Pharmacologic treatment of behavioral symptoms in autism and pervasive developmental disorders. Journal of Clinical Psychiatry, 66, 26-31.Handen, B.L. & Lubetsky, M. (2005). Pharmacotherapy in autism and related disorders. School Psychology Quarterly, 20, 155-171.Hollander, E. (2003). Autism Spectrum Disorders. New York, NY: Marcel Dekker, Inc. Hollander, E., Phillips, A.T., & Yeh, C. (2003). Targeted treatments for symptom domains in child and adolescent autism. The Lancet, 362, 732-734.Jacobson, J.W., Foxx, R.M., & Mulick, J.A. (2005). Controversial therapies for developmental disabilities: Fad, fashion, and science in professional practice. New York, NY: Routledge.

Matson, J.L. & Dempsey, T. (2008). Autism spectrum disorders: Pharmacotherapy for challenging behaviors. Journal of Developmental and Physical Disabilities, 20, 175-191.Matson, J.L. & Hess, J.A. (2010). Psychotropic drug efficacy and side effects for persons with autism spectrum disorders. Research in Autism Spectrum Disorders, 5, 230-236.Posey, D.J., Stigler, K.A., Erickson, C.A., & McDougle, C.J. (2008). Antipsychotics in the treatment of autism. The Journal of Clinical Investigation, 118, 6-14. Scahill, L. (2008). How do I decide whether or not to use medication for my child with autism? Should I try behavior therapy first?. Journal of Autism and Developmental Disorders, 38, 1197-1198.Self, T.L., Hale, L.S., & Crumrine, D. (2010). Pharmacotherapy and children with autism spectrum disorder: A tutorial for speech-language pathologists. Language, Speech, and Hearing Services in Schools, 41, 367- 375. United States Food and Drug Administration (n.d.) FDA approves risperdal for treatment of irritability associated with autistic disorder. Retrieved from http://www.fda.gov/Drugs/ScienceResearch/ResearchAreas/Pharmacogenetics/ucm237637.html.Volkmar, F.R. & Wiesner, L.A. (2009). A Practical Guide to Autism: What Every Parent, Family Member, and Teacher Needs to Know. Hoboken, NJ: John Wiley & Sons, Inc.West, L., Waldrop, J., & Brunssen, S. (2009). Pharmacologic treatment for the core deficits and associated symptoms of autism in children. Journal of Pediatric Health Care, 23, 75-89.

a review of pharmacotherapy for autism treatment by: bridget spanarkel

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