Transcript Neuro-Medical Aspects of Autism

The Important Questions to Ask
Before Considering Medications
Michael J. Murray, M.D.
Penn State College of Medicine
Milton S. Hershey Medical Center
Today’s Goals
• Questions to consider when thinking about
adding medication to the treatment plan
• Guidelines for interpreting the research on
medication
• A basic understanding of commonly used
medications for ASD
Beyond the Diagnosis
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Medication Management
Diagnosis of Comorbidities
Periodic Reassessment
Consultation with Other Treatment Providers
Therapy for the Individual
Therapy for the Family
Advocating for Best Practices
“Typical” Treatment team may
include…
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Primary Care Physician
Neurologist
Psychiatrist
Special Education
Teacher
• Behavior Analyst
• Speech Therapist
• Physical Therapist
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Occupational Therapist
Behavior Specialist
Therapeutic Staff Support
Personal Care Aides
Recreational Therapist
Parents, Self-Advocates
and Other Family
Members
Things to Consider
• What are the potential risks?
• How will potential adverse outcomes affect the
individual and the family?
• Has the treatment been validated scientifically?
• Are the assessment methods specified?
Things to Consider
• How will the treatment be integrated into the
individual’s other treatment interventions?
• Do not overvalue a given treatment such that
functional curriculum, vocational life, and social
skills are ignored.
Things to Consider
• Most importantly, need to gauge the social
validity of the proposed intervention with
the individual and family as appropriate
Social Validity
• Essentially asks, “How valuable is this?”
• Needs to be assessed before and
intermittently throughout the intervention
Interpreting Research Results
• Not all research is created equal
• The design of the study significantly contributes to
the strength of the research findings or observations
• The stronger the research design, the more reliable
the outcome
Case Report
• A detailed report of the diagnosis, treatment, and
follow-up of an individual patient.
• Also referred to as anecdotal report
• Of limited benefit aside from justifying pilot studies
Case Series
• A group or series of case reports involving patients
who were given similar treatment. Reports of case
series usually contain detailed information on
diagnosis, treatment, response to treatment, and
follow-up after treatment.
• Not hypothesis driven or controlled
Open Label Study
• A type of study in which both the health providers
and the patients are aware of the drug or treatment
being given.
• Used frequently as they are easier to conduct than
randomized studies and avoid ethical issues of
withholding treatment.
Randomized controlled trials
• The randomized, double-blinded, controlled clinical
trial is the gold standard of study design
• This design provides protection from allocation bias
by the investigator and from bias in assessment of
outcomes by both the investigator and the patient.
Non-Randomized Clinical Trials
• This category includes trials in which treatment allocation
was made by a strategy that would make the allocation
known to the investigator before informed consent is
obtained from the patient.
• An imbalance can occur in treatment allocation under such
circumstances.
Other things to consider…
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The larger the “N” the better
The more variables matched the better
The longer the treatment phase the better
The longer the follow-up the better
The more assessment measures the better
The smaller the “p” the better
Medication
There Is No Magic Bullet
• Only one medication (risperidone) has been approved by
the FDA as a treatment for autism spectrum disorders
(ASD).
• However many medications can be helpful in alleviating
some of the features of ASD.
• Medications can also treat the co-morbid disorders that
often accompany ASD.
Know What You’re Treating
• Have realistic and clear expectations for the trial.
• Helpful to have data to support (or refute) a medication’s
efficacy.
• Good communication is essential to ensure the child’s
optimal health and to increase the chance for success with
potential trials.
If considering a trial…
• Agree on a behavioral target, which is easily
operationalized in multiple environments, and
method of collecting data
• Establish a baseline of the behavior and perform
other assessment measures if indicated
• Helpful to have positive and negative targets, if
possible
While undergoing the trial…
• Continue collecting data at agreed upon intervals and
frequency
• Coordinate potential dose adjustments with other treatment
interventions
• Give medication doses adequate time to demonstrate
change (trends in behavior may take time to manifest)
• Helpful to graph data
This assumes good communication with the treatment team,
which can be a challenge in the “real world”.
However, some objective measure is necessary to determine
medication efficacy and treatment outcome.
Guiding Principles for ALL Trials.
Start Low (REALLY LOW).
Go Slow (REALLY SLOW).
Neurochemical Basis of Autism
• Literature primarily focused on two neurotransmitter
systems:
– Dopamine
– Serotonin
dopamine
• Atypical neuroleptics are the medications of choice to
address dopamine dysregulation
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Risperidone (Risperdal)*
Olanzapine (Zyprexa)
Quetiapine (Seroquel)
Aripiprazole (Abilify)
Atypical Neuroleptic Targets
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Self-injury
Severe agitation
Stereotyped movements
Severe behavior problems
RUPP Study
• Research Units in Pediatric Psychopharmacology
Autism Network
• Large multi-site trial of the short-term and long-term
safety and efficacy of risperidone in a group of over
100 children and adolescents with autism
RUPP Study
• Phase I
– 8 week double blind trial of placebo vs. risperidone
– 70% of those receiving medication rated as much or
very much improved (12% on placebo)
• Phase II
– 4 month open label extension of the study
– Benefits sustained at stable dose
RUPP Study
• Phase III
– Subjects randomly assigned to continue active substance or to
gradual withdrawal with placebo
– Relapse rate significantly higher in placebo group (although not
100%)
• Most common side effects
– Weight gain
– Sedation
– Drooling
serotonin
• Increase in blood serotonin
• Brain serotonin synthesis seems to be disrupted
• Post-pubertal children with autism have lower
serotonin concentrations than pre-pubertal children
with autism (opposite the typical pattern)
serotonin
• Selective Serotonin Reuptake Inhibitors (SSRI’s) are the
medications of choice to address serotonin dysregulation
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Fluoxetine (Prozac)
Fluvoxamine (Luvox)
Sertraline (Zoloft)
Citalopram (Celexa)
Escitalopram (Lexapro)
SSRI Targets
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Repetitive behaviors
Stereotyped mannerisms
Difficulty with change or transition
Anticipatory anxiety
Obsessive compulsive behaviors
Depression
The research
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Only small open label studies to date
A RUPP type study is underway for fluoxetine
Widely used clinically
Most common side effects
– Disinhibition
– Irritability
– Sleep disturbance
Other Clinical Concerns
• ADHD-like behaviors
– Stimulants can be helpful
– Growing clinical use of atomoxetine (Strattera)
• Mood Instability
– Anticonvulsants can be helpful
– Be cautious with lithium
Sleep Issues
• Children with autism have greater difficulty falling
asleep and more frequent awakenings to full
arousal during the night
• Can have significant impact on the child’s ability to
participate in programming
• Quality of life issue for the family
Sleep Issues
• If using medication for another indication, may try to
exploit the sedating side effect of a particular agent
• Importance of good sleep hygiene is particularly
important for this population
Trends in Medication Usage
• In 1995, a survey found that 30.5% of the
population sample were prescribed a
psychotropic medication
• In 1999, a survey of high functioning
individuals with autism found 55% taking
at least one psychotropic medication
Trends in Medication Usage
• A survey completed in 2006 found a
prevalence of 70.2% among individuals
with moderate autism
Factors Associated with Higher
Usage Rates
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Greater age
More severe autism
More severe intellectual limitations
Housing outside of the family home
Most Commonly Prescribed
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Antidepressants
Antipsychotics
Stimulants
Antihypertensives
Antiseizure medications
Thanks for listening.
Questions?
Michael Murray, M.D.
[email protected]
(717) 531-1115
References
Volkmar, F et al. Autism and pervasive developmental
disorders, Journal of Child Psychology and Psychiatry,
45:1 (2004), pp135-70.
• American Academy of Child and Adolescent Psychiatry,
Practice Parameters for the Assessment and Treatment
of Children, Adolescents, and Adults with Autism and
Other Pervasive Developmental Disorders, available at
www.aacap.org.