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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 Queen’s University. Objectives of This Talk:.

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so the diagnosis is autism now what an approach to the behavioral medical management

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 Queen’s University

objectives of this talk
Objectives of This Talk:
  • By the end of this talk, you should appreciate …
  • The widening definition of the Autistic Spectrum Disorders (ASD’s)
  • The physician’s role in treatment of ASD’s
    • Basic behavioral approaches
    • Rx of co-morbidities
methods utilized during this session
Methods Utilized during this session

Some didactic presentation

Case presentations (mine and yours?)

Interactive discussions with questions

facts about autism
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
other req ments for autism
Other Req’ments For Autism
  • Delays/abnormal functioning in at least 1 of following areas, onset <3 yrs
  • Social interaction
  • Language as used in social communication
  • Symbolic or imaginative play
  • Disturbance not due to Rett’s or CDD
in children with autism
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

the problems of co morbid diagnosis
The Problems of Co-morbid Diagnosis
  • DSM-IV somewhat arbitrarily imposes restrictions, e.g.
    • Can’t diagnose ADHD & autism
    • Can’t diagnose OCD & autism
    • Can diagnose Tourette’s & autism
  • Definitely a problem since clinicians CLEARLY see e.g. ADHD & autism, etc.
traits that vary in asd s
Traits That Vary in ASD’s

Measured I.Q.

Severe delay

Gifted

Social Interaction

Aloof

Passive

Active but Odd

Communication

Non-verbal

Verbal

(Gross)

Awkward

Agile

Motor Skills

(Fine)

Uncoordinated

Coordinated

Sensory

Hypo sensitive

Hypersensitive

co morbidities outcome
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 ASD’s have sleep issues)
  • Eating/nutritional issues
nutrition feeding issues in asd
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

eating dietary issues
Eating/Dietary Issues

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

  • Specifically, a study supported previous research that children with autism’s 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 ASD’s are susceptible to a variety of nutritional deficiencies! (Arnold et al, 2003, & others)
management options
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
sleep disturbance in autism
Sleep Disturbance in Autism

Williams PG, et al: J. Sleep Res., 13, 265–268; 2004

  • Sleep problems in children with autism
    • prevalence estimates of 44–83% for sleep disorders in this population
    • Poor appetite and poor growth were associated with decreased willingness to fall asleep
sleep disturbance in autism22
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 children’s 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)

treatment of insomnia
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
non traditional treatments
Non-traditional Treatments
  • Melatonin (MLT) & sleep:
  • 14 kids with “classic autism”were 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
melatonin in autistics
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
non pharmacologic rx s
Non-Pharmacologic Rx’s
  • May play a role in
    • Eating/dietary challenges 
    • Sensory disorders (SID’s) 
    • Sleeping disorders (some) 
    • Some aggressive behaviors 
    • The general management of ASD’s 
behavior management
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
sensory disorders
Sensory Disorders
  • Children with ASD’s are particularly susceptible to extremes of sensory vulnerabilities
  • Tactile
  • Auditory
  • Taste
  • Olfactory
the issues in considering medical intervention in this population
The Issues in Considering Medical Intervention in This Population…
  • No pharmacologic treatments have consistently been shown to decrease core symptoms of…
    • Social impairment &
    • Communication deficits…common to autism
the issues in considering medical intervention in this population32
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
caveats in treating asd s
Caveats In Treating ASD’s
  • 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 doesn’t teach the child anything!
caveats in treating asd s34
Caveats In Treating ASD’s
  • It may make the child more receptive to other educational or general management approaches, but it doesn’t replace them!
caveats in treating asd s35
Caveats In Treating ASD’s
  • 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,P:Practical Paediatric Psychopharmacological prescribing

in autism: The potential and the pitfalls. Autism 4 (3)

slide36
Mintz M, et al (2006)Treatment approaches for the ASDs. (From: Autism a neurological disorder of early brain development. Tuchman & Rapin, ICNA)
what medications have been looked at in the asd s
What Medications Have Been Looked at In the ASD’s
  • The stimulants e.g. methylphenidate (Ritalin®); Concerta®; Dexedrine®
  • Atomoxetine (Strattera®)
  • 2 Adrenergic-agonists
  • The antidepressants (SSRI’s and tricyclics)
  • The neuroleptics (antipsychotics)
    • Typical, e.g. haloperidol (Haldol®)
    • Atypical, e.g. risperidone (Risperdal®)
the psycho stimulants their role
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
the psycho stimulants their role40
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

the psycho stimulants their role41
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 al:1995: J of Autism & Developmental Disorders

Santosh et al,2006:

the psycho stimulants their role42
The Psycho-stimulants: Their Role
  • In higher functioning kids with ASD’s response is better, more predictable & often low doses are effective
  • In kids with cognitive impairment (IQ <45; mental ages <4.5), success is less likely, & idiosyncratic (negative) responses more likely, including agitation & stereotypies!
the neuroleptics antipsychotics
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

the neuroleptics antipsychotics46
The Neuroleptics (Antipsychotics)
  • Atypical Neuroleptics…continued:
  • 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.

2 adrenergic agonists
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

2 adrenergic agonists49
2-Adrenergic-agonists
  • Lofexidine recently evaluated in a small (n=12) 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

the antidepressants
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 SSRI’s
ssri s in autism
SSRI’s 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

ssri s in autism52
SSRI’s 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

defining the repetitive and compulsive behavior domain in autism spectrum disorder
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
sertraline s effectiveness was assessed in children in an open label trial
Sertraline’s effectiveness was assessed in children in an open-label trial

Steingard RJ et al: J Child AdolescPsychopharmacol. 1997;7(1):9–15.

  • 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.
citalopram celexa is one of the most highly selective ssris
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.
early intervention with selective serotonin reuptake inhibitors
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 dendriticarbors and somatosensory barrels, and a decrease in synaptic density
early intervention with selective serotonin reuptake inhibitors57
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.
newer options in autism
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
donepezil aricept in autism
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
slide60
Thank You

for your attention!

Questions??

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