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

1. 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

2. 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

3. Methods Utilized during this session Some didactic presentation Case presentations (mine and yours?) Interactive discussions with questions

4. 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

5. Autism :an Attempt to Simplify the Issues

6. 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

7. 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

8. 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.

9. 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

15. Intellectual Disability

16. Leyfer OT, et al: J Autism Dev Disord (2006) 36:849–861

17. 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

18. 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

19. 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)

20. 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

21. 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

22. 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)

23. Tuchman & Rapin (2006): Autism: A neurological disorder of early brain development.

24. 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

25. 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

26. 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

27. “To Treat or Not To Treat? That Is the Question!” Medical Treatment in Autism ?

28. 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 

29. 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

30. Sensory Disorders • Children with ASD’s are particularly susceptible to extremes of sensory vulnerabilities • Tactile • Auditory • Taste • Olfactory

31. 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

32. 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

33. 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!

34. 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!

35. 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)

36. Mintz M, et al (2006)Treatment approaches for the ASDs. (From: Autism a neurological disorder of early brain development. Tuchman & Rapin, ICNA)

38. 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®)

39. 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

40. 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

41. 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:

42. 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!

44. Hazell P:JPCH, 2007

45. 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

46. 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.

48. 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

49. 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

50. 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