So the diagnosis is autism Now WhatAn approach to the behavioral

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So the diagnosis is autism! Now What?An
approach to the behavioral medical management

• Dr. R. Garth Smith
• Developmental Pediatrician
• Medical Director
• Child Development Centre
• Hotel Dieu Hospital
• Associate Professor of Pediatrics Queens
  University

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Objectives of This Talk

• By the end of this talk, you should appreciate
• The widening definition of the Autistic Spectrum
  Disorders (ASDs)
• The physicians role in treatment of ASDs
• Basic behavioral approaches
• Rx of co-morbidities

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Methods Utilized during this session

• Some didactic presentation
• Case presentations (mine and yours?)
• Interactive discussions with questions

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Facts about Autism

• Autism is a brain-based disorder, onset prenatal
• Involves abnormalities in
• Qualitative aspects of social development
• Qualitative aspects of communication development
• Repetitive, stereotyped patterns of behavior
  interests
• Affects 4 males to 1 female
• Prevalence for autism is 1/500 prevalence for
  ASD is 1/150

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Autism an Attempt to Simplify the Issues
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Other Reqments For Autism

• Delays/abnormal functioning in at least 1 of
  following areas, onset lt3 yrs
• Social interaction
• Language as used in social communication
• Symbolic or imaginative play
• Disturbance not due to Retts or CDD

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In children with Autism

• As many as
• 60 have poor attention/concentration
• 40 hyperactive
• 88 with unusual preoccupations/rituals
• 37 with obsessive thinking
• 89 with stereotyped language
• 74 with significant fears/anxiety
• 44 with depressed mood, irritability agitation
• 11 with sleep problems
• 43 with self-injury
• 10 with tics
• Seizures in 14 of autistics with peaks in
  Infancy Adolescence
• A significant have feeding nutritional issues

Data from Gillberg, 2004
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The Problems of Co-morbid Diagnosis

• DSM-IV somewhat arbitrarily imposes restrictions,
  e.g.
• Cant diagnose ADHD autism
• Cant diagnose OCD autism
• Can diagnose Tourettes autism
• Definitely a problem since clinicians CLEARLY see
  e.g. ADHD autism, etc.

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Traits That Vary in ASDs
Measured I.Q.
Severe delay
Gifted
Social Interaction
Aloof
Active but Odd
Passive
Communication
Non-verbal
Verbal
Awkward
(Gross)
Agile
Motor Skills
Uncoordinated
(Fine)
Coordinated
Sensory
Hypo sensitive
Hypersensitive
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Intellectual Disability
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Leyfer OT, et al J Autism Dev Disord (2006)
36849861
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Co-morbidities Outcome

• Cognitive delay (ID/MR)(60 AD 30 ASD)
  (Fombonne, 2006)
• Seizure disorder (5 to 44) (Tuchman Rapin,
  2002 Lancet Neurol)
• Depression (? with age) esp with higher
  functioning individuals
• Anxiety disorders (all types)
• Sleep (up to 80 of children
  with ASDs have sleep issues)
• Eating/nutritional issues

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Nutrition/Feeding Issues in ASD

• Numerous case studies have reported dietary
  selectivity among children with autism
• Repetitive behaviors and restricted interests, a
  core feature of autism, may play a role in
  dietary selectivity
• Children with ASDs often resist novel
  experiences, which may include tasting new foods.
• Many children with ASDs have sensory
  hypersensitivities and may reject foods due to an
  aversion to texture, temperature or other
  characteristics of the foods (e.g appearance).

Herndon AC et al, 2008
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Eating/Dietary Issues

• Specifically, a study supported previous research
  that children with autisms eating behavior is
  restricted by
• Food category (Ahearn et al., 2001),
• By texture (Ahearn et al., 2001 Archer
  Szatmari, 1991), and
• These children refuse foods more often than
  typically developing children (Archer Szatmari,
  1991).
• Other studies have shown that kids with ASDs are
  susceptible to a variety of nutritional
  deficiencies! (Arnold et al, 2003, others)

Shreck KA et al Journal of Autism and
Developmental Disorders, Vol. 34, No. 4
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Management Options

• Nutritionist/dietician referral to evaluate
  intake adequacy
• Bloodwork (e.g. Ferritin, B12, pre-albumen, Zn,
  etc.)
• Referral to feeding team (where available) OT
  for sensory Rxs

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Sleep Disturbance in Autism

• Sleep problems in children with autism
• prevalence estimates of 4483 for sleep
  disorders in this population
• Poor appetite and poor growth were associated
  with decreased willingness to fall asleep

Williams PG, et al J. Sleep Res., 13, 265268
2004
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Sleep Disturbance in Autism

• Sleep problems are associated with other health
  conditions and quality of life
• Sleep deprivation appears to intensify the
  behavioral problems of autistic children,
  improved sleep may improve childrens behavior,
  alleviating maternal stress as a result (personal
  study)
• Decrease in quality sleep could be a source of
  stress that affects not only the child, but also
  other family members (Richdale, et al., 2000)

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Tuchman Rapin (2006) Autism A neurological
disorder of early brain development.
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Treatment of Insomnia

• The primary approach is so-called sleep hygiene
  or behavioral approaches (establishing
  routines, allowing to fall asleep alone, etc)
• It is only when these fail that medical
  approaches are entertained. These include
• Traditional Medicines, e.g. Trazodone, clonidine,
  etc
• Non-traditional approaches, e.g. Melatonin,
  tryptophan

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Non-traditional Treatments

• Melatonin (MLT) sleep
• 14 kids with classic autismwere studied
• No autistic patient showed a normal MLT circadian
  rhythm
• Moreover, autistic children showed significantly
  lower mean concentrations of MLT, mainly during
  the dark phase of the day, with respect to the
  values observed in the controls

Kulman G et al, 2000
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Melatonin in Autistics

• Melatonin (MLT) sleep
• Jan JE, O'Donnell ME (1996) reviewed 100 kids
  with a variety of developmental disabilities
  including Autism,
• Melatonin, which benefited slightly over 80 of
  their patients, appeared to be a safe,
  inexpensive, and a very effective treatment of
  sleep-wake cycle disorders
• Our study

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To Treat or Not To Treat? That Is the Question!
Medical Treatment in Autism
?
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Non-Pharmacologic Rxs

• May play a role in
• Eating/dietary challenges ?
• Sensory disorders (SIDs) ?
• Sleeping disorders (some) ?
• Some aggressive behaviors ?
• The general management of ASDs ?

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Behavior Management

• Use simple ABC approach
• E.g. may find that transitions create negative
  behaviors
• Advanced warning may help reduce these behaviors
• Avoidance of overstimulating (sensory overload)
  environments may ? improvements

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Sensory Disorders

• Children with ASDs are particularly susceptible
  to extremes of sensory vulnerabilities
• Tactile
• Auditory
• Taste
• Olfactory

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The Issues in Considering Medical Intervention in
This Population

• No pharmacologic treatments have consistently
  been shown to decrease core symptoms of
• Social impairment
• Communication deficitscommon to autism

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The Issues in Considering Medical Intervention in
This Population

• However, there is growing evidence of the
  efficacy of various medications in treating
  associated symptoms of autism including
• Aggression, agitation
• Hyperactivity, inattention
• Irritability
• Repetitive behaviors stereotypies
• Self-injury
• Sleep disorders

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Caveats In Treating ASDs

• The fact that a child meets criteria for autism
  is not a sufficient indication for prescribing
  psycho-pharmacological agents
• Medication may affect physiology and behavior and
  may even teach us more about some of the signs
  symptoms shown in autism other disorders, but
  it doesnt teach the child anything!

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Caveats In Treating ASDs

• It may make the child more receptive to other
  educational or general management approaches, but
  it doesnt replace them!

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Caveats In Treating ASDs

• Behavior modification strategies educational
  placements with high teacher student ratios have
  been shown to reduce stereotyped behaviors
  improve aspects of communication socialization
  (Campbell et al., 1996).

Gringras,PPractical Paediatric
Psychopharmacological prescribing in autism The
potential and the pitfalls. Autism 4 (3)
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Mintz M, et al (2006)Treatment approaches for the
ASDs. (From Autism a neurological disorder of
early brain development. Tuchman Rapin, ICNA)
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What Medications Have Been Looked at In the ASDs

• The stimulants e.g. methylphenidate (Ritalin)
  Concerta Dexedrine
• Atomoxetine (Strattera)
• ?2 Adrenergic-agonists
• The antidepressants (SSRIs and tricyclics)
• The neuroleptics (antipsychotics)
• Typical, e.g. haloperidol (Haldol)
• Atypical, e.g. risperidone (Risperdal)

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The Psycho-stimulants Their Role

• Significant hyperactivity can exist with autism
  Asperger syndrome (10-20) (Ghaziuddin,1998
  Martin et al, 1999)
• These medications act by increasing the
  neurotransmitters norepinephrine dopamine
  indirectly in the brain (CNS)
• For years they were not used in kids with Autism
  as it was claimed that they increased negativism
  (including self-injurious behaviors), tics
  stereotypies

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The Psycho-stimulants Their Role

• In 1995, however, Quintana et al described in an
  excellent study, that there was a
  statistically significant reduction in
  hyperactivity without an increase in stereotypic
  behaviour, using methylphenidate
• In some kids, adverse effects are seen, including
  ? irritability, paradoxical ? in hyperactivity,
  stereotypic behaviors, or agitation

Aman et al, 2000
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The Psycho-stimulants Their Role

• Santosh et al (2006) found positive results in
  ADHD autism
• Some kids had ? obsessionality (use lower
  dosages, and ? slowly) (Aman)

Quintana et al1995 J of Autism Developmental
Disorders
Santosh et al,2006
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The Psycho-stimulants Their Role

• In higher functioning kids with ASDs response is
  better, more predictable often low doses are
  effective
• In kids with cognitive impairment (IQ lt45 mental
  ages lt4.5), success is less likely,
  idiosyncratic (negative) responses more likely,
  including agitation stereotypies!

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Hazell PJPCH, 2007
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The Neuroleptics (Antipsychotics)

• Atypical Neuroleptics
• Risperidone is the most studied
• These are potent antagonists at serotonin
  dopamine, have a lower incidence of TD and
  dystonias
• Improvements noted in irritability,
  hyperactivity, aggression, repetitive behaviors,
  oppositionality self-injury (/- anxiety)
• Weight gain was the most significant side effect
  (up to 16kg)in children may stabilize over time

Hardan A et al,1996 Findling RL et al, 1997,
Nicolson R et al,1998, Pandina et al 2007
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The Neuroleptics (Antipsychotics)

• Atypical Neurolepticscontinued
• New! RUPP study (2003) recently completed
• Risperidone was superior to placebo in reducing
  symptoms of most concern to parents of autistic
  children with irritable behavior (2003)
• Some evidence of the benefits of risperidone in
  irritability, repetition and social withdrawal
  were apparent (2007)
• Other atypical neuroleptics have been less
  studied but appear no better and olanzapine did
  not improve repetitive behaviors
• Continued efficacy relative safety noted up to
  one year in a group of autistic kids with
  risperidone

Arnold LE et al,2003 Nicolson R et al,1998
Jesner O, Aref-Adib M,Coren E,2007 Pandina et
al, 2007.
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?2-Adrenergic-agonists

• Clonidine Guanfacine are best studied
• ?ed noradrenergic neurotransmission
• Good study with clonidine ?Improvement in
  hyperactivity, irritability, stereotypes,
  inappropriate speech oppositional behavior
  (only 8 kids used!)
• Was a double-blind, placebo-controlled, crossover
  study
• Adverse effects were sedation,irritability
  hypotension

Jaselskis et al, 1992
Guanfacine effective in 22 Posey
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?2-Adrenergic-agonists

• Lofexidine recently evaluated in a small (n12)
  but well-done study
• They used it for kids with autistic disorder PLUS
  hyperactivity, distractibility and impulsivity
• Results rated by parents, teachers, and
  clinicians (viewed videos)
• Modest improvement in only hyperactivity(without
  sedation)noted

Niederhofer et al, Dec., 2002
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The Antidepressants

• Tricyclic non-selective serotonin reuptake
  inhibitor e.g. Clomipramine
• In an excellent study by Gordon et al (1993)this
  drug was more effective than placebo in treating
  some symptoms e.g. anger/uncooperativeness,
  hyperactivity, OCD symptoms
• But, side effects of irregular heart rhythm,
  lowering of seizure threshold , make it less
  desirable than the SSRIs

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SSRIs in Autism

• Fluvoxamine has shown excellent results in adult
  autistics with few side effects?decreased
  repetitive thoughts behavior, maladaptive
  behavior aggression and improved communication
• In children, in contrast, the results were not as
  consistent, esp. in younger kids
• Adverse effects included insomnia, motor
  hyperactivity, agitation, aggression anxiety
  (esp. pre-pubertal)

McDougle et al, 2002
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SSRIs in Autism

• Why this difference? Unknown!
• Fluoxetine (Prozac) showed effectiveness but
  intolerable side effects as above.
• Sertraline (Zoloft) was useful in 1 adult study
  (better with Autism and PDD-NOS than Asperger
  syndrome)

McDougle, 1998
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Defining the repetitive and compulsive behavior
domain in autismspectrum disorder

• A preoccupation with stereotyped and restricted
  patterns of interest
• Inflexibility in adhering to routines and rituals
• Stereotyped and repetitive motor mannerisms
• Persistent preoccupation with parts of objects

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Sertralines effectiveness was assessed in
children in an open-label trial

• Nine children with autism between the ages of 6
  and 12 were administered sertraline for the
  treatment of transition-associated anxiety and
  agitation.
• It was found that 89 of the subjects had a
  positive response.
• Results suggest the importance of future
  controlled investigation of sertraline in
  pediatric and adult ASD populations.

Steingard RJ et al J Child Adolesc
Psychopharmacol. 19977(1)915.
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Citalopram (Celexa) is one of the most highly
selective SSRIs

• A published open-label, chart-review of
  citalopram in 15 children and adolescents who had
  PDDs suggested
• improvements in repetitive behaviors and
• anxiety based on CGI-S and CGI-I ratings 49.
• The study reported a mean dose of citalopram was
  16.9 mg plus or minus 12.1 mg daily (range 5 to
  40 mg), with children treated over an average
  period of 218.8 plus or minus 167.2 days.
• Of the 15 cases, 11 were much improved or very
  much improved.
• The longer the subject was on the treatment, the
  more positive the response. As noted, anxiety and
  repetitive behaviors or stereotypies were most
  responsive to citalopram, with 10 of the 15
  subjects showing improvement in anxiety,
  presumably related to reduced rigidity in
  adherence to routines and rituals.
• Although length of treatment time correlated
  positively with response, higher dosages did not.

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Early intervention with selective serotonin
reuptake inhibitors

• SSRIs have been presented as a model
  pharmacologic treatment, because serotonin is
  known to enhance synapse refinement in the brains
  of autistic children
• In the developing cortex, serotonin is concerned
  with maturation of thalamic afferents, cortical
  dendrites, and axons, with alterations in the
  levels of serotonin potentially resulting in
  negative effects.
• High levels of serotonin may reduce pruning of
  the dendritic branches
• Too little serotonin causing a smaller number of
  dendritic spines than usual, miniscule dendritic
  arbors and somatosensory barrels, and a decrease
  in synaptic density

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Early intervention with selective serotonin
reuptake inhibitors

• Interventions targeting normalization of
  serotonin regulation in the developing brain of
  young children who have autism has been proposed
  as a novel, early intervention strategy
• A pilot, randomized, placebo-controlled trial is
  being funded by the NIH STAART network in
  toddlers and preschoolers who have autism to
  evaluate the effects of liquid fluoxetine on
  global improvements and alterations in
  developmental progressions in young children who
  have ASDs.

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Newer Options in Autism

• In light of the recently reported neuropathologic
  and neurochemical abnormalities of the
  cholinergic pathways in autism
• Donepezil,Aricept, a cholinesterase inhibitor, is
  a potentially useful agent in the treatment of
  cognitive and behavioral symptoms observed in
  this disorder
• Eight patients (mean age 11.0 /- 4.1 years
  range 7-19 years)were openly treated

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Donepezil, Aricept in Autism

• Four of these patients (50) demonstrated
  significant improvement as assessed by the
  Aberrant Behavior Checklist and the Clinical
  Global Impression Scale.
• Decreases in the Irritability and Hyperactivity
  subscales were observed
• But no changes in the Inappropriate Speech,
  Lethargy, and Stereotypies subscales were noted
• Limited and transient side effects were reported,
  with one patient experiencing gastrointestinal
  disturbances and another reporting mild
  irritability

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Thank You
for your attention!
Questions??