autism latest update

1. Prepared by:
Dr Shakirrul Faqih Bin Ishak
FMS trainee Hospital Port
Dickson
Supervisor:
Dr Norliza Paidi

2. ⦿1ST described by Leo Kanner in 1943 as early infantile autism
⦿“ Auto”- children are “locked within themselves”.
⦿For the 30 years, considered to be an emotional
disturbance.
⦿Lauretta Bender first used the term “childhood
schizophrenia” for childhood autism.

3. Prevalence
• On March (2014), CDC USA showed that overall
prevalence of ASD is 14.7 per 1000 (1 in 68) children
aged 8 years.( 1 in 42 boys and 1 in 189 girls).
• Smaller scale study by MOH in 2006 on children between
18 to 26 months showed ~ 1.6 in 1000 children or ~ 1 in
625
• 4 times more prevalent in boys
• Many cases go undetected, hence true prevalence rate of
ASD in Malaysia is higher.
• No known racial, ethnic or social boundaries

4. Introduction
• Autism Spectrum Disorder (ASD) is a
neurodevelopmental disorder characterised
by impairments in communication,
behaviour and social functioning which
begin in childhood
• It typically appears during the 1st three years
of life, due to a neurological disorder
that affects the functioning of the brain
• Aetiology unclear
• Multifactorial:
• genetic vulnerability
• environmental factors

5. Autism comes from Greek word ‘autos’,
“ Auto”- children are “locked within themselves”.

6. 3 Impairments!!
• COMMUNICATION
• SOCIAL FUNCTIONING
• BEHAVIOUR
Situasi di Klinik Kesihatan
1. Anak saya tak dengar bila saya panggil nama. Dia ada masalah pendengaran ke? (Follow up M-
CHAT)
2. Anak saya ni memilih sangat makan. Sebelum makan dia akan hidu makanan dulu. Dia cuma
makan benda rangup. (Follow up KBB)
3. JM at KK : Dr kena tengok la anak Mrs xxx , saya tengok anak dia macam hyper waktu homevisit
melompat, memanjat sana sini. Malam-malam tak tidur.
(during antenatal clinic day)
4. Cikgu suruh saya bawak anak dtg klinik, sebab cikgu cakap dia “slow” kat sekolah .
5. Dr, saya nak minta Dr sahkan anak saya OKU sebab dia ni “slow learner”.
6. Referral from LINUS program

7. Why should know this topic?
• It is predominantly clinical diagnosis
• Wide range of difficulties
– emotional
– attentional
– thought
– behavioural
– eating problem
– medical problems
+ comobidities >>> significant clinical impairment

8. • Typically appears during the 1st three years of life, due to a
neurological disorder that affects the functioning of the brain
• Aetiology unclear
• Multifactorial:
• genetic vulnerability
• environmental factors

9.  Parental age – the most consistently studied
risk factor
 Risk for ASD increases with parental age
 Maternal age:
• >35 years old vs 25 - 29 years old (OR = 1.31, 95%
CI 1.19 to 1.45)1
• >40 years old vs <30 years old (OR = 2.1, 95% CI
1.48 to 2.86)2
1. Sandin S, et al. J Am Acad Child Adolesc Psychiatry. 2012, 51(5):477-486
2. Guinchat V, et al. Acta Obstet Gynecol Scand. 2012, 91(3):287-300
9

10.  Paternal age: compared to ≤29 years old:3
• 40 - 49 years old (OR = 1.42, 95% CI 1.07 to 1.87)
• ≥ 50 years old (OR = 2.21, 95% CI 1.26 to 3.88)
• ≥ 55 years old (OR = 4.36, 95% CI 2.09 to 9.09)
 First born of mother aged >35 years old &
father aged >40 years old vs parents aged 25
- 29 years old, adjusted OR = 3.1, 95% CI 2.0
to 4.74
3. Hultman CM, et al. Mol Psychiatry. 2011, 16(12):1203-1212
4. Durkin MS, et al. Am J Epidemiol. 2008, 168(11):1268-1276
10

11.  Prematurity (<37 weeks of gestation) in
particular those born <33 weeks are at risk
of developing ASD (OR = 5.4, 95% CI 1.1
to 27.7)2
2. Guinchat V, et al. Acta Obstet Gynecol Scand. 2012, 91(3):287-300
11

12.  Neonatal encephalopathy has OR for ASD
ranging from 3.06 to 5.59.2
2. Guinchat V, et al. Acta Obstet Gynecol Scand. 2012, 91(3):287-300
12

13.  The adjusted relative recurrence risk of ASD is
increased with increasing genetic relatedness.1
• Monozygotic twins = 153.0 (95% CI 56.7 to 412.8)
• Dizygotic twins = 8.2 (95% CI 3.7 to 18.1)
• Full siblings = 10.3 (95% CI 9.4 to 11.3)
• Maternal half-siblings = 3.3 (95% CI 2.6 to 4.2)
• Paternal half-siblings = 2.9 (95% CI 2.2 to 3.7)
• Cousins = 2.0 (95% CI 1.8 to 2.2)
The RR of ASD for infants with multiple older affected siblings is significantly 2.2
times higher than those who had only one older affected sibling.2

14.  The following appear to offer some benefit
especially in those who are genetically
susceptible:
• Use of folic acid supplement in mothers around
the time of conception (4 weeks before & 8
weeks after pregnancy)6
• Peri-conceptional prenatal vitamin intake7
6. Suren P, et al. JAMA, 2013, 309(6):570-577
7. Schmidt RJ, et al. Epidemiology. 2011, 22(4):476-485

15.  Cochrane systematic review of 10 studies
found no significant association between
MMR immunisation & autism.8
 Increasing exposure to antibody-
stimulating proteins & polysaccharides in
vaccines during the first 2 years of life was
not associated with risk of developing
ASD.9
8. Demicheli V, et al. Cochrane Database Syst Rev.2012,2:CD004407
9. DeStefano F, et al. J Paediatrics. 2013, 163(2):561-567

17.  The aetiology of ASD is multi-factorial &
unclear.
 Factors associated with increased risk of
ASD include advancing parental age,
prematurity, neonatal encephalopathy &
genetic relatedness.
 MMR & other immunisation are not
associated with ASD.

18. CLINICAL PRESENTATION &
FEATURES OF AUTISM

19. • Delayor abnormalfunctioningin at least oneofthefollowingarea:
1. Social skills - socialinteraction/understanding
2. Language- communicationskills
3. Behaviors- restricted,repetitiveactivities andinterests
AND
Early onset: beforeageof 3

20. SocialImpairment
• Lackof socialempathy(fail to recognize
othersemotion):
Doesn't respondtoparent'ssmileor other
facial expressions
Unableto perceivewhatothersmightbe
thinkingorfeelingbylookingat their facial
expressions
Doesn't showconcern(empathy) for others
• Maybeaffectionate, butontheir term,
withouttheexpectedjoyandreciprocity

22. CommunicationImpairment
• Involve all modeof communications: speechandlanguage,
intonation,gesture, facial expression,bodylanguage
• Bothreceptiveandexpressivelanguage:
 Loseslanguagemilestones,usuallybetweentheagesof15to24
monthsin afewchildren (regression)
 Doesn't saysinglewordsby15monthsor 2-wordphrases by24
months

23. CommunicationImpairment
• Stereotypedandrepetitiveoridiosyncraticuseofwords
 Echolalia,pronounreversal,inventedwords:Repeatsexactlywhat
otherssaywithoutunderstandingitsmeaning(parrotingorecholalia)
• Difficulttoinitiateorsustainaconversationwithothers:
 Oftendoesn'tseemtowanttocommunicate
 Doesn'tstartorcan'tcontinueaconversation

24. Communicationdifferences
• Doesn'trespondtonamebeingcalled,butdoesrespondtoothersounds(likeacar
hornoracat'smeow)
• Referstoselfas"you"andothersas"I"(pronominalreversal)
• Doesn'tusetoysorotherobjectstorepresentpeopleorreallifeinpretend
play
• Mayhaveagoodrotememory,especiallyfornumbers,songs,TVjingles,ora
specifictopic

26. Repetitivestereotyped behavior,activitiesandinterest
• Rigidandinflexiblethought processes
• Resistanceto change,insistonsameroutines, ritualistic
behaviour:
 Likesroutines, order, andrituals
 Obsessedwithafewactivities, doingthemrepeatedlyduringtheday
• Repetitivebehaviour andinterest e.g.
 fascinatedwith samesegmentofTVshow,Rocks,spins,sways,twirls
fingers, or flapshands(stereotypicbehavior)
 Playswithpartsoftoysinsteadof thewholetoy(for example,spinning
thewheelsof atoytruck)
• Lackof pretendplay

28. Stehen Wilthshire

29. V
enice byStehenWiltshire
(2008)

30. Behavioral differences
• Mayhavesplinter skills, suchastheability toreadat an
earlyage, but oftenwithout understanding what it means
• Doesn'tcryif in painorseemtohaveanyfear
• Maybeverysensitiveornotsensitiveatall to
smells, sounds, lights, textures, andtouch
• Unusual useof visionor gaze—looksat objects from
unusual angles

36. 1
Slides by:
Dr. Toh Teck Hock Paediatrician & Head
of CRC Sibu Hospital

37. ⦿Limited studies on the effectiveness
of screening tools
37
⦿SRs1,2,3: better performing tools for ASD of
young children are:
o Checklist for Autism in Toddler (CHAT)
o Modified Checklist for Autism in Toddlers (M-CHAT)
o Social Communication Questionnaire (SCQ)
1. Sunita, Bilszta JLC. J Paediatr Child Health. 2013, 49(6):438-444
2. Norris M, & Lecavalier L. Autism. 2010, 14(4):263-284
3. Mawlea E, & Griffiths P
. Int J Nurs Stud. 2006m 43(5):623-636

38. ⦿A 23-item questionnaire on child behaviour &
development reported by parents for young
children
⦿Malay & Chinese versions for local use in
Malaysian healthcare facilities
⦿T
raining is required for interpretation of the
result.
M-CHAT
38

40. M-CHAT
Chinese
T
ranslation
40

41. ⦿The bold items are critical: i.e. 2, 7, 9, 13, 14, 15
⦿A child requires referral (i.e. fail M-CHA
T) for
further evaluation if he/she fulfils the following:
o 2 or more of critical items
o 3 or more of any items 41

42. 42
Specificity: 70 - 98%
Sensitivity: 27 – 43%
⦿Positive predictive value: 5.8% to 76%
⦿Better at detecting autism in:
◾ children aged 24 months vs 18 months
◾ high risk group in early intervention programme centres (vs low risk group in routine baby clinic)
Not allchildren who fail the checklist will meet criteriafor adiagnosis
on the autism spectrum disorder (ASD).
Note:

43. ◾Recommended for use:1
o at 18 months - early identification
o at 24 months - identify those with regression
◾May be used in children up to 30 months of
age if misses earlier screening
1. Sunita, Bilszta JLC. J Paediatr Child Health. 2013, 49(6):438-444
43

44. Regardless of the screening result, children suspected of ASD
at any age by the family or other care providers should be
referred for evaluation.
44

45. ⦿A parent-rated questionnaire on children aged
above 4 years
⦿Evaluates social interaction, language,
communication & stereotypic behaviours for
possible autism or other ASD
⦿Better in detecting ASD in those over 7 years
old (sensitivity: 86%-90%; specificity: 78%-86%)
vs children 2-3 years old (sensitivity: 47%-54%;
specificity: 89%-92%)
45

46. ⦿Broadband developmental screening tools:
46
◾Child Behaviour Checklist (CBCL)
◾Infant-toddler checklist (ITC)
◾Parents’ Evaluation of Developmental Status (PEDS)
⦿Screening tools specific for ASD:
◾Checklist for Autism in Toddlers (CHAT)
◾Checklist for Autism in Toddlers for Chinese Children
(CHAT-23)
◾Modified Checklist for Autism in Toddlers, Revised with
Follow-up
◾Gilliam Autism Rating Scale/Gilliam Autism Rating Scale
Second Edition (GARS/GARS-2)
◾Social Responsiveness Scale (SRS)
◾Autism Spectrum Screening Questionnaire (ASSQ)
◾Asperger Syndrome Diagnostic Scale (ASDS)

47. Dr. Ranjini S. Sivanesom
Consultant Developmental Paediatrician
Institute of Paediatrics
Hospital Kuala Lumpur
47

48. • History (ideally from the main caretaker &
others who are involved in the care of the child)
• Symptoms e.g. poor eye contact, lack of
response to name, impaired visual tracking of
an object, poor social interaction, poor
reciprocal communication, repetitive behaviour,
restricted interests & limited ability to imitate
• Developmental history (including regression)
48

49. • Behavioural problems
• Medical history (prenatal & perinatal)
• Psychiatric history (co-existing mental disorders
e.g. depression & anxiety)
• Family history (any developmental disorders)
• Social history (school, home life, physical
environment, social needs)
• Medication & allergy history
49

50. • General examination (any dysmorphism,
detailed neurological examination)
• Developmental assessment (for baseline
developmental age equivalent)
• Audiology (for hearing assessment)
• Visual
• Signs of physical abuse/self-harm
50

51. Neuro-
developmental
disorders
Mental &
behavioural
disorders
Conditions with
developmental
regression
Other conditions
Specific
language delay
ADHD Rett Syndrome Severe hearing
impairment
Global
developmental
delay
Mood disorder Epileptic
encephalopathy
Severe visual
impairment
Developmental
coordination
disorder
Anxiety disorder Maltreatment
Attachment disorder Selective mutism
ODD
Conduct disorder
OCD
Psychosis
51

52. DSM-5CLASSIFICA
TION
Neurodevelopmental Disorder
Intellectual Disabilities
Communication Disorders
AutismSpectrumDisorder
Attention-Deficit/ Hyperactivity
Disorder
SpecificLearning Disorder
Motor Disorderss
Other Neurodevelopmental
Disorders

53. A. Persistent deficits in social communication & social
interaction, as manifested by the
following, currently or by history:
1. Deficits in social - emotional reciprocity
2. Deficits in nonverbal communicative
behaviors used for social interaction
3. Deficits in developing, maintaining & understanding
relationships
53

54. B. Restricted, repetitive patterns of behavior, interests or activities
as manifested by at least two of the following:
1. Stereotyped or repetitive motor movements, use of objects or
speech
2. Insistence on sameness, inflexible adherence to routines or
ritualized patterns of verbal or nonverbal behavior
3. Highly restricted, fixated interests that are abnormal in intensity or
focus
4. Hyper- or hyporeactivity to sensory input or unusual interest in
sensory aspects of the environment
54

55. C. Symptoms must be present in the early developmental period (but may
not become fully manifest until social demands exceed limited capacities, or
may be masked by learned strategies in later life).
D. Symptoms cause clinically significant impairment in social, occupational
or other important areas of current functioning.
E. These disturbances are not better explained by intellectual disability or
global developmental delay.
55

59. Severity level Social communication Restricted, repetitive behaviours
Level 3
"Requiring
very
substantial
support"
Severe deficits in social
communication skills, very limited
initiation of social interactions &
minimal response to social
overtures from others
Inflexibility of behaviour, extreme
difficulty coping with change, or
other restricted/repetitive
behaviours markedly interfere with
functioning in all spheres
Great distress/difficulty changing
focus or action
Level 2
"Requiring
substantial
support"
Marked deficits in social
communication skills, limited
initiation of social interactions &
reduced or abnormal responses
to social overtures from others
Obvious interference with
functioning in a variety of contexts
Distress &/or difficulty changing
focus or action
Level 1
"Requiring
support"
Without supports in place,
deficits in social communication
cause noticeable impairments
Difficulty initiating social
interactions & atypical responses
to social overtures of others
Inflexibility of behaviour causes
significant interference with
functioning in one or more contexts
Difficulty switching between
activities
Problems of organisation & planning
hamper independence
59

60. Specify if:
With or without accompanying intellectual impairment
With or without accompanying language impairment
Associated with a known medical or genetic condition or
environmental factor
Associated with another neurodevelopmental, mental or
behavioural disorder
With catatonia
60

61. Example 1
 Autism Spectrum Disorder with Level 1 SCI & Level 1 RRB
Example 2
 Autism Spectrum Disorder with Level 2 SCI & Level 1 RRB with ADHD
Example 3
 Autism Spectrum Disorder with Level 1 SCI & Level 2 RRB Symptomatic
Generalised Epilepsy
Example 4
 Tuberous sclerosis Autism Spectrum Disorder with level 1 SCI & level 1
RRB
61

62. • ASD is a clinical diagnosis & need not require
standardised assessment tools.
• Diagnosis may not be made at the first appointment.
• Early diagnosis is important for prompt intervention.
• Refer to experts when in doubt.
62

63. Dr. Farahidah Md Dai
HOD &
Consultant Child & Adolescents Psychiatrist
Hospital Sultanah Aminah
1

64. 1. Intellectual disability - half of ASD especially extreme autistic trait 1,2
2. Attention deficit hyperactivity disorder (ADHD)3:
- 53% children with ASD haveADHD
22% - hyperactivity/impulsivity
46% - inattentive
32% - combined
- are usually younger
- have a lower mean IQ
3. Sleep problems4, 5 - night walking, sleep onset problem
4. Epilepsy6,7,8
- the prevalence of epilepsy in ASD ranges from 7-46%.
- increases with symptomatic autism, associated psychiatric disorder, use of psychotropic
meds, history of cognitive/developmental regression
5. Motor incoordination9 - affects handwriting and motor skills

66. 6. Gastrointestinal problems9,10,11
◾Children with ASD 5 times more common to have feeding problems
than those without ASD.
◾Type of problems:
o Food selectivity
o Food refusal
o Behavioural rigidity during meals
o Combination of above
◾They tend to have a higher level of nutritional inadequacies with
lower consumption of calcium and protein.
◾There is an increased incidence of constipation in these children.
9. Sharp WG,et al. J Autism Dev Disord. 2013, 43(9):2159-2173
10 . Marí-Bauset S, et al. J Child Neurol. 2013, [Epub ahead of print]
11. Ibrahim SH, et al. Pediatrics. 2009, 124(2):680-686
8

68. 7. Psychiatric disorders13
◾70.8% have at least one current psychiatric disorder
◾57% have multiple diagnosis:
o 62.8% have ADHD, emotional & behavioural disorders
o 24.7% have Tourette’s syndrome, chronic tics, etc.
o 41.9% have anxiety or phobic disorder
o 30% have oppositional or conduct problems
o 1.4% have depressive disorder
◾There is no substantial evidence on the prevalence of
psychosis in children with ASD.
13. Simonoff E, et al. J Am Acad Child Adolesc Psychiatry. 2008, 47(8):921-929
68

69. Investigation
• ASD is predominantly a clinical diagnosis.
• Children withASD generally do not require intensive investigation.
• Investigations may be carried out in some children withASD to
• establish underlying pathology
• exclude treatable conditions
• identify co-morbid conditions
Aim: T
o rule out hearing impairment
o ABR/BSER (Auditory Brainstem Evoked Response) - measures the hearing nerve’s response to sound

70. ABR/BSER
70

71. • Genetic & metabolic studies are not routinely done in children with ASD as
the association with inherited metabolic disorders is low.3
• Ix are done when there is a suspicion of syndromes such as
◾ Fragile X syndrome
◾ dysmorphism
◾ macrocephaly &/or
◾ severe intellectual disability or global developmental delay
• These children have to be referred to a paediatrician or a
geneticist for further evaluation.4
• There is insufficient evidence to support the use of EEG in the
investigation of children with ASD without clinical seizures.1, 2

72. ⦿Brain imaging is not routinely done in patients with ASD as
◾ evidence do not show any difference in the brains of children with
ASD & controls.5
⦿Brain imaging is usually considered in selective cases where
syndromes or neurological conditions are suspected & is
usually done at tertiary levels.6
5. Via E, et al. Arch Gen Psychiatry. 2011, 68(4):409-418
6. Boddaert N, et al. PLoS One. 2009, 4(2):e4415
72

73. 73

75. 1. APPLIED BEHAVIOUR ANALYSIS (ABA)
2. COGNITIVE BEHAVIORAL THERAPY
2. SPEECH, LANGUANGE AND COMMUNICATION INTERVENTION
3. OCCUPATIONAL THERAPY
75

76. Applied Behaviour Analysis (ABA)
• Applied Behaviour Analysis (ABA) is the application of
behavioural principles (positive reinforcement) to
everyday situations, that will over time increases or
decreases targeted behaviours
• Evidence showed that ABA should be considered as
one of the management for children with ASD.
• ABA is conducted by trained psychologist.
RECOMMENDATION 6
●Applied Behaviour Analysis should be considered in the
management of children with autism spectrum disorder. (Grade A)

79. SPEECH THERAPY

80. The earlier, the better!!!!!
Children with ASD who
receive therapy between 2-3
years old showed
improvement in expressive
language skills at 4 years old.1
SPEECH THERAPY
1. Stone WL & Yoder, PJ. Autism, 2001, 5(4):341-361
80

81. 2. Fernande FD, et al. Pro Fono Revista de Atualizacao Cientifica. 2008, 20(4):267-272
3. Tamanaha AC & Perissinoto J. J Soc Bras Fonoaudio. 2011, 2391): 8-12
Parent participation is vital to a
child’s success.
Involvement of family members in the
therapy helps
 increase the number of communication
acts & use of communication means2
 decrease autism behaviour & increase
typical communication3
81

82. • Occupational therapy provides assessment &
intervention to promote skill development &
optimise independence in daily activities.
• Occupational therapy may combine a variety of
strategies/approaches.
82

84. • Often used by occupational therapists to manage children
with ASD8
• Involves provision of sensory input by using appropriate
modalities
8. Ayres AJ & Tickle LS. Am J Occup Ther, 1980, 34:375-381
84

87. 87

88. • Improve deficits in the skills in children with ASD6
• Social skill intervention - improvement in overall social
competence & friendship quality7
6. Flynn L, Healy O. Res in Autism Spectr Disord. 2012, 6 (1):431-441
7. Reichow B, Steiner AM, Volkmar F. Cochrane Database Syst Rev. 2012 7:CD008511
Self-help Skills Social Skills
88

89. • Refers to the child’s capacity to coordinate attention
with a social partner around an object or event12
• Improves joint attention in teacher-child play & joint
engagement in mother-child play13
12. Mundy P & Sigman M. Developmental Psychopathology (2nd edi). 2006 : 293-332
13..Kaale A, et al. J Child Psychol Psychiatry. 2012, 53(1):97-105
89

90.  Involves movement related skills such as
eye hand coordination
 Increased the attention span of children
with ASD14
14. Afshari J. Res. Autism Spectr Disord. 2012, 6:1331-1336
90

91. 91

94. ⦿ In ASD, medications are used generally in the
treatment of co-morbid disorders.
⦿Conventional antipsychotics such as haloperidol are
used less frequently due to its high incidence of severe
adverse reactions.
⦿The use of atypical antipsychotics in ASD is preferred
due to the reduced propensity of causing
extrapyramidal symptoms.

96. a) Risperidone
⦿ 5-18 years,
<50Kg: Initial dose 0.25mg OD(optimum dose0.5mgOD)
>50kg: Initial dose 0.5mg OD(optimum dose 1 mgOD)
⦿ A meta-analysis suggested that short-term use of
risperidone significantly improved:2
-irritability
-social withdrawal/lethargy
-hyperactivity
-stereotype
-inappropriate speech
Associated with higher risk of weight gain
1. McCracken JT, et al. N Engl J Med. 2002, 347(5):314-321
2. Jesner OS, et al. Cochrane Database Syst Rev. 2007, (1):CD005040

97. b) Aripiprazole
⦿ A meta-analysis suggested that aripiprazole
up to 15 mg/day might be efficacious in
treating:3
-irritability
-hyperactivity
-stereotypy
-inappropriate speech
⦿ Adverse effects - weight gain, sedation,
drooling & tremor
3. Ching H, et al. Cochrane Database Syst Rev. 2012,5:CD009043

98. c)Olanzapine4
⦿Dose up to 20 mg/day improves CGI-I (Clinical Global Impression
Improvement Scale) score in pervasive developmental disorder
(PDD) at 8 weeks
⦿Associated with significant weight gain
d)Paliperidone5
⦿Dose up to 12 mg/day is efficacious for irritability
⦿Safety profile is acceptable except for raised prolactin level in
males
4. Hollander E, et al. J Child Adolesc Psychopharmacol. 2006, 16(5):541-548
5. Stigler KA, et al. Psychopharmacology. 2012, 223(2):237-245

99. e) Quetiapine6
⦿Low dose (≤150 mg/day) is efficacious in
reducing aggression & improving sleep quality in
children with ASD at 8 weeks
⦿No significant difference in body weight & the
adverse effects were mild
f) Ziprasidone7
⦿Dose up to 160 mg/day is efficacious in reducing
irritability & hyperactivity in autism at 6 weeks
⦿QTc prolongation may offset the arguably
minimal benefits associated with its use
6. Golubchik P
, et al. Clin Neuropharmacol. 2011, 34(6):216-219
7. Malone RP, et al. J Child Adolesc Psychopharmacol. 2007, 17(6):779-790

100. ⦿ Limited & conflicting evidence of effect & side effects.9
9. Hurwitz R, et al. Cochrane Database Syst Rev. 2012 (3):CD008372
⦿ No evidence of SSRI effect in children with ASD on core
symptoms & severity of the disorder
⦿Emerging evidence of harm e.g. seizure, poor appetite
& weight loss8
.
8. Williams K, et al. Cochrane Database Syst Rev. 2010 (8):CD004677

101. a) Methylphenidate10
⦿ More efficacious than placebo among subjects who have
PDD (Pervasive Developmental Disorder)
⦿ Dosage : over 6 years 5mg OD/BD, increases to 5-10mg
daily (max dose 60mg daily)
⦿ Side effects - loss of appetite, sleep difficulties &
irritability
10. Research Units on Pediatric Psychopharmacology Autism Network. Arch Gen Psychiatry.
2005, 62(11):1266-1274

102. b) Atomoxetine
⦿ Limited evidence of efficacy in children with ASD & ADHD
symptoms.11
11. Ghanizadeh A. J Atten Disord. 2013, 17(635-640)
c) Valproate12
⦿ Divalproate sodium significantly reduced irritability compared
to the placebo
⦿ The findings were robust even after controlling for
intelligence quotient (IQ) differences
⦿ Side effects were mild to moderate & resolved with small
changes in dosing & did not require discontinuation
12. Hollander E, et al. Neuropsychopharmacology, 2010, 35(4):990-998

103. d)Melatonin
⦿ Melatonin is an endogenous neurohormone produced predominantly in
the pineal gland.13
⦿ In a meta-analysis, melatonin was more
efficacious than placebo in the treatment of ASD in terms of:14
◾ increased sleep duration by 44 minutes
◾ shorter sleep onset latency by 39 minutes
⦿ Combination of CBT (Cognitive Behaviour
Therapy) & melatonin was statistically most
efficacious in reducing insomnia symptoms
compared to either modality or placebo when used alone.15
⦿ Reported mild side effects - headache, diarrhoea & dizziness.14
13. Johnson KP
, et al. Child Adolesc Psychiatr Clin N Am. 2008, 17:773-785
14. Rossignol D, et al. Dev Med Child Neurol. 2011, 53(9):783-792
15. Cortesi F, et al. J Sleep Res. 2012, 21(6):700-709

105. ⦿The following treatment modalities have poor evidence, no
effectiveness &/or some harmful effects in children with ASD:
◾chelation16, secretin17, fatty acids18, vitamin B6- magnesium19,
vitamin B1220, acupuncture21 & hyperbaric oxygen therapy22
⦿There is no retrievable evidence for vit. A, vit. C,
trimethylglycine, cupping, ayurvedic medicine or
homeopathy in the treatment of children with ASD.
16. Davisa TN et al. Res Autism Spectr Disord. 2013, 7 (1):49-55
17. William K, et al. Cochrane Database Syst Rev. 2012, (4) : CD003497
18. James S, et al. Cochrane Database Syst Rev. 2011, (11):CD007992
19. Nye C, et al. Cochrane Database Syst Rev. 2005, (4):CD003497
20. Bertoglio K, et al. J Altern Complement Med. 2010, 16(5):555-560
21. Cheuk DKL, et al. Cochrane Database Syst Rev. 2011, (9):CD007849
22. Magiati I, et al. J Intellect Disabil Res. 2011, 55(3):302-312

106. REFERENCES
1. CPG Management of Autism Spectrum Disorder in Children
and Adolescents
2. Training Module Management of Autism Spectrum Disorder in
Children and Adolescents