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Clinical Practice Guidelines forPractice Parameters or Childhood Autism

Dr. Usha S Naik

Professor and HOD of Psychiatry Osmania Medical College &Niloufer Hospital, Hyderabad

Autism and the related pervasive developmental disorders (PDDs) are characterized by patterns of delay anddeviance in the development of social, communicative, and cognitive skills, which arise in the first years of life.In 1943 Dr. Leo Kanner studied a group of 11 children manifesting with unusual symptoms of aloofness andodd behaviour with areas of exceptional development .These children were apparently in a world of their ownand to this disorder the name infantile autism was given. Kanner’s classic description still holds good today andchildren with autism still manifest the same symptom triad of impaired social relatedness, and communicationwith a restricted repertoire of behaviour. The pervasive developmental disorders, or autism spectrum disorders,range from a severe form, called autistic disorder, to a milder form,Asperger syndrome. Other rare, very severedisorders that are included in the autism spectrum disorders are Rett’s syndrome and childhood disintegrativedisorder..

The following aspects of the disorder will be considered

The Changing face of ChildhoodAutism

Prevalence

Some recent controversies

Etiology

Assessment

Treatment

Prognosis

Review of Randomized Controlled studies in Treatment ofAutism

In the past few decades , our understanding of childhoodAutism has changed considerably.

!) More Cases is this due to an increase in referrals / or wider spectrum of diagnosis for inclusion /or realincrease in incidence

Nature of Onset Earlier the disorder was reported to be present from birth with the subtle early signs havingbeen missed .Today an increasing number of cases are being reported where, children develop normallyinitially but regress in language, communication and behaviour usually in the second year of life .

Etiology An interplay of a genetic predisposition and environmental insults are more likely to result inautism than any single factor.

Treatment Behavioural, educational and pharmacological measures should be paired with Bio medicalInterventions

Prognosis Children are showing substantial improvement in many cases with recovery in some childrenwhere treatment is started early enough

A)

B)

C)

D)

E)

F)

G)

H)

A) THE CHANGING FACE OFCHILDHOODAUTISM

2)

3)

4)

5)

B) PREVALENCE

C) SOME RECENT CONTROVERSIES

D) Etiology

In 2007 - the most recent government survey on the rate of autism - the Centers for Disease Control (CDC)found that the rate is higher than the rates found from studies conducted in the United States during the1980s and early 1990s (survey based on data from 2000 and 2002). The CDC survey assigned a diagnosisof autism spectrum disorder based on health and school records of 8 year olds in 14 communitiesthroughout the U.S. Debate continues about whether this represents a true increase in the prevalence ofautism. Changes in the criteria used to diagnose autism, along with increased recognition of the disorderby professionals and the public may all be contributing factors. Nonetheless, the CDC report confirmsother recent epidemiological studies documenting that more children are being diagnosed with an ASDthan ever before.

Data from an earlier report of the CDC’sAtlanta-based program found the rate of autism spectrum disorderwas 3.4 per 1,000 for children 3 to 10 years of age. Summarizing this and several other major studies onautism prevalence, CDC estimates that 2–6 per 1,000 (from 1 in 500 to 1 in 150) children have an ASD.The risk is 3-4 times higher in males than females. Compared to the prevalence of other childhoodconditions, this rate is lower than the rate of mental retardation (9.7 per 1,000 children), but higher than therates for cerebral palsy (2.8 per 1,000 children), hearing loss (1.1 per 1,000 children), and visionimpairment (0.9 per 1,000 children .

There are several controversies raging in the field of Childhood Autism They mainly concern etiologyand management practices

The vaccine controversy is a classic controversy. group of scientists and parents believe that vaccines havean important etiological role in autism . However the Institute of Medicine (IOM) conducted a thoroughreview on the issue of a link between thimerosal (a mercury based preservative that is no longer used invaccinations) and autism. The final report from IOM stated that the committee did not find a link.

Until 1999, vaccines given to infants to protect them against diphtheria, tetanus, pertussis,type b (Hib), and Hepatitis B contained thimerosal as a preservative.

Today, with the exception of some flu vaccines, none of the vaccines used in the U.S. to protect preschoolaged children against 12 infectious diseases contain thimerosal as a preservative. The MMR vaccine doesnot and never did contain thimerosal. Varicella (chickenpox), inactivated polio (IPV), and pneumococcalconjugate vaccines have also never contained thimerosal.

AU.S. study looking at environmental factors including exposure to mercury, lead and other heavy metalsis ongoing.

Similarly here are several treatment methods based on differing concepts and these have very strongreports in favour of and against a particular practice .

Whereas in the past the focus was on a search for chromosomal causes the search has become much finerand it is now DNAalterations ,specific enzymes and the interplay of several genes that is being consideredas etiologically important .

A Study conducted by the Department with the CDFD by high-pressure liquid chromatographydemonstrated

Higher levels of

Glutamate, High

Haemophilusinfluenzae

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Hydroxy proline and lower levels of

Phenylalanine

,Proline

and Tryprophan .

E )

The evaluation checklist has been lengthened considerably. However a form based on DM IV will beuseful as it will

serve as diagnostic tool as well as a history taking one . In addition it becomes necessary to take a detailedevaluation

regarding Regression seen in the majority of children being referred to the department .

Nearly 70% of children showed regression in previously acquired skills with qualitative or quantitative changein the particular skill lost . Most children regressed between 12-18 months .

Adetailed history should include:

, Progress of labour and Mode of delivery, Birth asphyxia,Hyperbilrubinemia, Neonatal infections and other neonatal complications, Detailed Immunization Record

: Age of attaining important Milestones ,particularly Birth to two years**.Particular attention should be paid to details as they can prove very informative in understanding pathways ofdevelopment.

Two specific questions seem relevant-How did the child appear at the first birthday

How did the child appear at the second birthday ?Language and Social Milestones need to be reviewed with thefollowing questions: Achieved eg Mama ,Daddy Specific with meaning, Achieved and continue example

ASSESSMENTS

Age of Regression and area of regression(AKanakalata 2007)

EVALUATION FORMAT FOR CHILDREN WITHAUTISM

HISTORY

A) Prenatal and perinatal problems

B)Developmental Milestones

Language Social Play

No Regression 10 (19.6 %) !0 10

Regression

before one year

21.5 % 7.8 % -

Regression between 12

18 months

41.1 % 37.2 % 9.8%

Regression between 2

36

months

5.8% 5.8% 2 %

Developmental delay 11.7 % 49 % 88%

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Mama Daddy with meaning,Achieved and continue without meaning example Mama Daddy repeats withoutreference to parent, Milestone lost, Milestone lost and regained with meaning /without meaning

MILESTONES BIRTH TO TWOYEARS

C) History of:

D A record of abnormal behaviour

Seizures, Visual and hearing problems, Frequent ear infections, Physical trauma,

Separation or other stressful event- like being locked up accidentally or deliberately

can be made in the DSM IV format .It saves time in reaching a diagnosisand serves to illustrate to parents, the reason for the diagnosis.

CHECK LIST FOR SYMPTOMS INAUTISM

THIS check list if it contains 6 items of which at least

Two should be from (1) and one each from (2) and (3) to fulfill DSM IV Criteria forAutism

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E) FAMILYHISTORYOFAUTISM ,ADHD,SLD, OCD IN PARENTS

F) PHYSICALEXAMINATION INCLUDING NEUROLOGICALASSESSMENT

G) OBSERVATIONAND MSE

H) PSYCHOLOGICAL AND LANGUAGEASSESSMENT

INVESTIGATIONS

DIFFERENTIALDIAGNOSIS

TREATMENT

Particularly look for café au lait spots

Observation Look for Smile, Greeting, Interest in people,Aloofness, preoccupied with object, Self-stimulatoryor stereotyped behaviour, Hyperactivity, Tantrums. Watch the child playing while the interview is proceeding

Particularly observe if the child makes eye contact, Smiles responsively, Responds to parent calling name

Obeys instructions, Uses words ,Make requests through words, gestures or by dragging mother

Developmental Testing separately for Gross motor, Language, Personal & social and Fine motor areas .

The Seguin form Board was reported by Kanner and children with autism does well on form boards ascompared to other aspects of testing. Formal Intelligence testing is difficult to complete as children are oftennot co operative but WISC may be tried. For language assessment, the REELS ( Receptive ExpressiveEmergent Language Scale) are useful and give separate scales for receptive and expressive language. TheCARS or Childhood Autism Rating Scale is very commonly used and is a good instrument for monitoringchange with treatment.The Vineland’s Social Behaviour Rating Scale gives a good indication of social skills.ATEC which is a check list of theAutism Research Institute cis available on line .

More specialized instruments require specialized training like the A- DOS and the ADI- R and these areconsidered the assessment and evaluation gold standards .

I) Audiolgical Assessment is sometimes indicated particularly as many parents report the child cannot hear.Very often it turns out that the child has very selective hearing and may rush into the room when a particulartheme tune is played but listen to no other auditory stimuli.

J)

Where possible the following tests are recommended

1) Chromosomal testing including DNAAnalysis for Fragile X

2) Metabolic Profile for amino acid analysis

3) Lead and Mercury screening

4) EEG,

5) Imaging only if there is further regression –CT or MRI

ADHD, Speech and Language disorder , Selective mutism , Reactive attachment disorder ,OCD

Other PDDs like Retts, Childhood Disintegrative Disorder,Asperger’s,

Schizophrenia, Mental retardation which may be Co morbid -as many as 70 % of children

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The goals of treatment are two fold : to reduce disruptive behaviour and to increase communication andlearning. Treatment will depend on the age at the time of referral.

Guidelines used by the Autism Society of America include the following questions parents should ask aboutpotential treatments:

Will the treatment result in harm to my child?

Has the treatment been validated scientifically?

How will the treatment be integrated into my child’s current program? Do not become so infatuated with agiven treatment that functional curriculum, vocational life, and social skills are ignored.

The National Institute of Mental Health suggests a list of questions parents can ask when planning for theirchild:

How successful has the program been for other children ?

How many children have gone on to placement in a regular school and how have they performed?

Do staff members have training and experience in working with children and adolescents with autism?

How are activities planned and organized?

Are there predictable daily schedules and routines?

How much individual attention will my child receive?

How is progress measured? Will my child’s behavior be closely observed and recorded?

Will my child be given tasks and rewards that are personally motivating?

Is the environment designed to minimize distractions?

Will the program prepare me to continue the therapy at home?

What is the cost, time commitment, and location of the program?

The different treatment options can be bewildering .Put simply children need to receive a combination ofPsycho educational approaches and Medical Interventions .

Lord and Bailey have suggested the following :

Diagnosis ,Prognosos an Teatment

Genetic Counselling

Correction of Hearing Loss

Dental care

Overall Treatment Programme

1. Feed Back to Family

2. Medical Care

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Correction of Medical Problems when present

Suitable class or adequately supported inclusion

Extra services required

Transition planning

Behavioural measures

Speech and Language training

Social groups

Medication where needed

Other psychological therapies

Behavioural measures

Counseling

Practical help

Support andAdvocacy group

Respite

In view of the multidisciplinary nature of working with a child with autism one clinician should be the primarytherapist .

The important areas to focus on are

1) Education through psychosocial Interventions

2) Help for the family

3) Medication

4) Specific therapies and

Sustained improvement or actual claims for cure have been made following intensive early behavioralintervention. There is no doubt that early and sustained intervention is indicated, but the duration and intensityand availability of therapists all need to be considered

The best interventions are the most intensive and focused .The best known programme is the ABA (AppliedBehaviour Analysis )of Lovaas which uses one on one interaction between the adult and the child through

3. Special education Provision

4. Treatment of specific problems or deficits

5. Help for family

1) EDUCATION THROUGH PSYCHOSOCIALINTERVENTIONS

EDUCATIONAL INTERVENTIONS

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repeated presentations to elicit a specific response .In use with young children excellent reports exist wherechildren may be indistinguishable from normal .However the method needs more than 24 hours a week oftreatment, requires highly trained and motivated therapists and an be quite expensive .

The TEACCH Treatment of Children andAdolescents withAutism and other Communicative Disorders is hasbeen used in India .our department has completed as tudy using the teach AND dietary intervention with goodsuccess . Inthis study 51 children wit autism who did not have delayed motor milestones were included in thestudy .They were given the TEACCH based model of services which included pspycho educational approachon an individualized basis .Treatment was continued for 18 months with reassessments every 6,12 and eighteen,months .Children showed significant improvement in Reduction of Autistic behaviours and improvement inboth receptive and expressive language. The PEPR showed equally significant change as did the Parental stressscores .

PValue

CARS 43.2 32.1 0.001

REELS

Receptive 28,5 47.9 0.001

REELS Expressive 33.5 56.5 0.001

PEPR 27.9 58.5 0.001

Developmental Profile

The evidence suggests that intensive educational interventions need to commence early and should be highlystructured to help the child develop communicative and social skills with simultaneous behaviouralimprovement

Successful educational programmes use learning principles to increase wanted behaviors and/or decreasemaladaptive behaviors These measures facilitate acquisition of skills

Lord has discussed that Behavioural methods should be used to :

Promote cognitive development and learning including academic and work skills

Promote language and communication particularly social use

Promote social development including problem solving

Reduction of maladaptive behaviour by distraction, avoiding precipitants and providing coping skills

Family support is essential and can help relieve the tremendous stress faced by parents of children withAutism.Parent groups serve this purpose .Breaking the news can be a difficult procedure as many parents have heardodd autism and cannot believe it is happening to them, Continuity of care which is essential may be difficult toprovide .Parents have a great need to know more about this problem and literature can help to a certain extent

IMPROVEMENT IN 51 CHILDRENAFTER 18 MONTHS FOLLOW UP.

Schedule Baseline Post treatment Significance

BEHAVIORALINTERVENTIONS

FAMILYSUPPORT

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though nothing can substitute for time spent with the family.

.On October 6, 2006 the U.S. Food and Drug Administration (FDA) approved risperidone for the symptomatictreatment of irritability in autistic children and adolescents ages 5 to 16. The approval is the first for the use of adrug to treat behaviors associated with autism in children. These behaviors are included under the generalheading of irritability, and include aggression, deliberate self-injury and temper tantrums.

Olanzapine and other antipsychotic medications are used “off-label” for the treatment of aggression and otherserious behavioral disturbances in children, including children with autism. Off-label means a doctor willprescribe a medication to treat a disorder or in an age group that is not included among those approved by theFDA.

Other medications are used to address symptoms or other disorders in children with autism. Fluoxetine andsertraline are approved for children age 7 and older with obsessive-compulsive disorder. Fluoxetine is alsoapproved for children age 8 and older for the treatment of depression.

Fluoxetine and sertraline are antidepressants known as selective serotonin reuptake inhibitors (SSRIs). Despitethe relative safety and popularity of SSRIs and other antidepressants, some studies have suggested that theymay have unintentional effects on some people, especially adolescents and young adults. In 2004, after athorough review of data, the Food and Drug Administration (FDA) adopted a “black box” warning label on allantidepressant medications to alert the public about the potential increased risk of suicidal thinking or attemptsin children and adolescents taking antidepressants. In 2007, the agency extended the warning to include youngadults up to age 25. A “black box” warning is the most serious type of warning on prescription drug labeling.The warning emphasizes that children, adolescents and young adults taking antidepressants should be closelymonitored, especially during the initial weeks of treatment, for any worsening depression, suicidal thinking orbehavior, or any unusual changes in behavior such as sleeplessness, agitation, or withdrawal from normalsocial situations.

The selective serotonin reuptake inhibitors (SSRI’s) are the medicationsmost often prescribed for symptoms of anxiety, depression, and/or obsessive-compulsive disorder (OCD).Only one of the SSRI’s, fluoxetine, has been approved by the FDAfor both OCD and depression in children age7 and older. Three that have been approved for OCD are fluvoxamine , age 8 and older; sertraline , age 6 andolder; and clomipramine , age 10 and older. Treatment with these medications can be associated with decreasedfrequency of repetitive, ritualistic behavior and improvements in eye contact and social contacts. The FDA isstudying and analyzing data to better understand how to use the SSRI’s safely, effectively, and at the lowestdose possible.

Antipsychotic medications have been used to treat severe behavioralproblems. These medications work by reducing the activity in the brain of the neurotransmitter dopamine.Among the older, typical antipsychotics, such as haloperidol , thioridazine, fluphenazine, and chlorpromazine,haloperidol was found in more than one study to be more effective than a placebo in treating serious behavioralproblems. However, haloperidol, while helpful for reducing symptoms of aggression, can also have adverseside effects, such as sedation, muscle stiffness, and abnormal movements.

Placebo-controlled studies of the newer “atypical” antipsychotics are being conducted on children with autism.The first such study, conducted by the NIMH-supported Research Units on Pediatric Psychopharmacology(RUPP) Autism Network, was on risperidone .Results of the 8-week study were reported in 2002 and showedthat risperidone was effective and well tolerated for the treatment of severe behavioral problems in childrenwith autism. The most common side effects were increased appetite, weight gain and sedation. Further long-term studies are needed to determine any long-term side effects. Other atypical antipsychotics that have beenstudied recently with encouraging results are olanzapine and ziprasidone . Ziprasidone has not been associated

3) MEDICATION

ANXIETY AND DEPRESSION.

BEHAVIORAL PROBLEMS.

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with significant weight gain.

Seizures are found in one in four persons with ASD, most often in those who have low IQ or aremute. They are treated with one or more of the anticonvulsants. These include such medications ascarbamazepine lamotrigine topiramate , and valproic acid . The level of the medication in the blood should bemonitored carefully and adjusted so that the least amount possible is used to be effective. Although medicationusually reduces the number of seizures, it cannot always eliminate them.

Stimulant medications such as methylphenidate andAtomoxetine , used safely and effectively in persons with attention deficit hyperactivity disorder, have alsobeen prescribed for children with autism. These medications may decrease impulsivity and hyperactivity insome children, especially those higher functioning children.

Several other medications have been used to treat ASD symptoms; among them are other antidepressants,Naltrexone, lithium, and some of the benzodiazepines such as diazepam and lorazepam . The safety andefficacy of these medications in children with autism has not been proven. Since people may responddifferently to different medications, your child’s unique history and behavior will help your doctor decidewhich medication might be most beneficial.

On October 6, 2006 the U.S. Food and Drug Administration (FDA) approved risperidone (generic name) orRisperdal (brand name) for the symptomatic treatment of irritability in autistic children and adolescents ages 5to 16. The approval is the first for the use of a drug to treat behaviors associated with autism in children. Thesebehaviors are included under the general heading of irritability, and include aggression, deliberate self-injuryand temper tantrums.

Olanzapine and otherAntipsychotic medications are used “off-label” for the treatment of aggression and otherserious behavioral disturbances in children, including children with autism. Off-label means a doctor willprescribe a medication to treat a disorder or in an age group that is not included among those approved by theFDA.

Other medications are used to address symptoms or other disorders in children with autism. Fluoxetine andsertraline are approved by the FDA for children age 7 and older with obsessive-compulsive disorder.Fluoxetine is also approved for children age 8 and older for the treatment of depression.

Fluoxetine and sertraline are antidepressants known as selective serotonin reuptake inhibitors (SSRIs). Despitethe relative safety and popularity of SSRIs and other antidepressants, some studies have suggested that theymay have unintentional effects on some people, especially adolescents and young adults. In 2004, after athorough review of data, the Food and Drug Administration (FDA) adopted a “black box” warning label on allantidepressant medications to alert the public about the potential increased risk of suicidal thinking or attemptsin children and adolescents taking antidepressants. In 2007, the agency extended the warning to include youngadults up to age 25. A “black box” warning is the most serious type of warning on prescription drug labeling.The warning emphasizes that children, adolescents and young adults taking antidepressants should be closelymonitored, especially during the initial weeks of treatment, for any worsening depression, suicidal thinking orbehavior, or any unusual changes in behavior such as sleeplessness, agitation, or withdrawal from normal socialsituations.

Many specific therapies are reportedly successful in Autism .These include Speech therapy ,cognitivebehaviour therapy , sensory integration. Many of these therapies can only be focused on once the child becomesresponsive .

Many non established treatments abound and parent should be cautioned against those likely to be dangerous.

SEIZURES.

INATTENTION AND HYPERACTIVITY.

4) SPECIFIC THERAPIES

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Age based treatment summariesBirth to five years

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Dietary Therapy

All cases attending the Niloufer Hospital are started on a gluten free,caesin free diet and many children begin toshow improvement in eye contact, language, and responsiveness within days to weeks. Hyperactivity does notimprove completely and many children are subsequently diagnosed to be hyperactive at other centres.

.The latest Comprehensive textbook reports

PROGNOSIS

Adiet that some parents have found was helpful to their autistic child is a gluten-free, casein-free diet. Gluten isa casein-like substance that is found in the seeds of various cereal plants—wheat, oat, rye, and barley. Casein isthe principal protein in milk. Since gluten and milk are found in many of foods following a gluten-free, casein-free diet is difficult.

A supplement that some parents feel is beneficial for an autistic child is Vitamin B6, taken with magnesium(which makes the vitamin effective). The result of research studies is mixed; some children respond positively,some negatively, some not at all or very little.

Regular follow up is required .Patients often shop for treatment so ideally all services can be offered in onesetting but this has been mostly difficult to achieve. Children seem to carry a better prognosis than previouslythought,though documentation is urgently required .

“ Autism is a lifelong disability with most individuals needingsignificant family and community support. It does appear to be the case that with earlier intervention, long termout come improves for many individuals with perhaps 15 % able to achieve independence and self sufficiency

5

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in adulthood and perhaps another 20 % of individuals able to function with reasonable support. However theimprovement in children that is so remarkably taking placerequires us to adopt a less pessimistic attitude .

Areview of the recent controlled studies both in Psycho educational and medical interventions follows .Studieswere reviewed over the past 5 years from Pub med and are summarized below :

1) Early Intervention for Children withAutism

2) Review of Drugs used in PDD

H) REVIEW OFRANDOMIZED CONTROLLED STUDIES IN TREATMENT OFAUTISM

3) OTHER BIOMEDICALINTERVENTIONS

1) EARLY INTERVENTION FOR CHILDREN WITH AUTISM

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APPENDIX 1 INDIAN STUDIES

In view of the growing number of referrals of children with autism the Indian Association ofPediattrics has decided to implemtnt cetain stpsAccording to the PresidentialAdress of the IAP,

INDIAN STUDIES

APPENDIX 2SPECIALMENTION -THE GLUTEN-FREE, CASEIN-FREE (GFCF) DIET

“Towards this goal, the IndianAcademy of Pediatrics has taken a path-breaking Programme on ChildhoodAutism under the IAP Vision 2007 where the pediatrician, as the first-line professional to every child, isbest placed to provide the guiding light. The program aims at increasing awareness of Autism amongmedical professionals, facilitation of services and rehabilitation of cases withAutism, as outlined below:

( ) Improve awareness of Autism among medical professionals, especially pediatricians who as frontlinedoctors may pick up the cases early;

( ) Survey and epidemiological study;( ) Facilitation of services for management and rehabilitation of cases withAutism,( ) Serve as a support group for the parents of children withAutism( ) Contribute to the research and study ofAutism.

We sincerely hope this initiative from IAPside will go a long way in decreasing the misery of children withAutism Spectrum Disorders.” Naveen Thacker ,

1 Nagaraj R, Singhi P, Malhi P.Risperidone in children with autism: randomized, placebo-controlled, double-blindstudy.J Child Neurol. 2006 Jun;21(6):450-5.2. Epidemiological Profile of Children With Autism in Comparison With Other Communicatively

Challenged Children Attending Early Intervention Centre Indian Journal of CommunityMedicineAuthor(s): S. Jayarama, J. S. Bhat Vol. 29, No. 3 (2004-07 - 2004-09)

3. Chandrashekhar B, Malla N, Vishalakshi. Early identification of autism issues and solutions, The J ofIndian Speech and HearingAssociation, 2002; 16:71-82.

Somestudies are hhighlighted .

Cade and colleagues (1999), conducted a study of 270 individuals. One hundred and twenty of theseparticipants were diagnosed with schizophrenia, and 149 met the DSM III criteria for a diagnosis of autism.Allchildren with autism were treated with a GFCF diet. During the study, parents, physicians and some teachersindependently assessed the children for the presence and severity of the diagnostic manifestations of autismusing a 4-point Likert scale. These ratings were done initially and repeated after 1 month of treatment and thenevery 3 months for 1 year. Parent and physician reports were averaged, with variability of individual observerscores reported as less than 10%. Blood samples were examined to measure the absorption of peptidescontained in wheat products (gluten) and dairy (casein) and the associated antibodies, immunoglobulin G (IgG)and transindolylacryloylglycine (IgA) for each of these food products. The study found that 87% of the childrenwith autism had high titer IgG antibodies to gliadin, and 30% had high titer IgA antibodies to gluten or caseinprior to initiation of the diet. Treatment with a GFCF diet was accompanied by reports of improvement in 81%of children within 3 months. A strength of this work was the combined use of physiological and behavioralmeasures. The behavioral results are limited, however, by the reliance on reports from parents and teachers whoknew that the children were on the GFCF diet.In a comparative study, Arnold, Hyman, Mooney, and Kirby(2003) evaluated amino acid patterns of 26 children with autism on a regular diet, 10 on a gluten-casein free

a

bcde

President, IAP 2007

,

DietaryTherapyThough controversial ,it is good to read the NIH publication refers to dietary therapy. While awaiting the

results of on going trials ,it is imperative that dietary therapy be given at least a three-month trial for each child.Empirical treatment of this kind is warranted because ,the prognosis is generally reported to be poor

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diet, and 26 with developmental delays who served as controls. The children with autism had higherdeficiencies in essential amino acids compared to the control group. These findings suggest that children withautism are at high risk for amino acid deficiencies and may benefit from a structured diet. Clearly, this is an areathat warrants further investigation. The authors note that a major limitation in the study was the small sample.An additional concern is the lack of strict dietary control for children on gluten-casein free diets, a commonlyencountered problem in conducting dietary research in children.Knvisberg (2002) and others conducted anRCT with 20 cases in children with autism and urinary peptide abnormalities .The experimental group showedsignificant changes over the control group in autistic behaviour,non verbal cognition and motor problems.Elder and colleagues (2006) in an RCT could not find significant change though parent sreportedinmprovement in the experimental group.

J Chritison G, IvanyDev Behav Pediatr., Volume 27, Issue 2(Suppl), p.S162-S171 (2006)

ndings.Careful double-blind, placebo-controlled studies are needed to evaluate whether actual benefit undergirds thediets’ popularity and to provide better guidance to clinicians and caregivers. The literature currently availablesuggests that diets eliminating both gluten and casein (rather than either alone) should be studied first and thatoutcome measures should include assessments of nonverbal cognition.

1. J Chritison G, Ivany Elimination Diets in Autism Spectrum Diorders Any Wheat amg ht chaff Dev BehavPediatr., Volume 27, Issue 2(Suppl), p.S162-S171 (2006)

2. Arnold, G.L., Hyman, S.L., Mooney, & R., Kirby, R.S., (2003). Plasma amino acids profiles in childrenwith autism: Potential risk for nutritional deficiencies.

, 449–454.

3. Cade, R., Privette, R.M., Fregly, M., Rowland, N., Sun, Z., Zele, V., et al. (1999). Autism andschizophrenia: Intestinal disorders. , 57-72.

4. Elder, J.H., Shankar, M, Shuster, J., Theriaque, D., Burns, S. & Sherrill, L. (2006). The Gluten-Free,Casein-Free Diet In Autism: Results Of A Preliminary Double Blind Clinical Trial.

, 413-420.

Knivsberg, A.M., Reichelt, K.L., Hoien, T., & Nodland M. (2002). A randomized, controlled study ofdietary intervention in autistic syndromes. , 251–261.

ThePractice parameters for the assessment and treatment of children, adolescents, and adults with autism and

Abstract: Elimination Diets in Autism Spectrum Diorders Any Wheat amidst thechaff ?The use of complementary or alternative treatment approaches in children with autism spectrumdisorders (ASDs) is increasing, and the most popular of such approaches are diets that eliminate eithergluten or casein, or both. The popularity of these diets indicates a need for more rigorous research intotheir efficacy. Owing to significant methodological flaws, the currently available data are inadequate toguide treatment recommendations. The purpose of this review is to examine the available trials ofgluten/casein diets in children with ASDs regarding the strength of their findings and also concerningpoints that may be useful in the design of future studies. Seven trials of these diets in ASD are criticallyreviewed; 6 of these were uncontrolled trials and 1 used a single-blind design. All reported efficacy inreducing some autism symptoms, and 2 groups of investigators also reported improvement in nonverbalcognition. Design flaws in all of the studies weaken the confidence that can be placed in their fi

GFCFREFERENCES :

5.

Appendix 3Sources and references The important sources were

i) AACAP parameters

Journal of Autism and Developmental Disorders,33

Nutritional Neuroscience, 2

Journal of Autism andRelated Disorders, 36

Nutritional Neuroscience, 5

i)Principle Authors: Fred Volkmar, M.D., Ed Cook, Jr., M.D., John Pomeroy

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other pervasive developmental disorders. American Academy of Child and Adolescent PsychiatryWorking Group on Quality Issues. Volkmar F, Cook EH, Pomeroy J, Realmuto G, Tanguay P J AM AcadChildAdolesc Psychiatry 1999;(12 Supppl):328-348

The –citation included –Strock, Margaret (2004). Autism Spectrum Disorders (Pervasive Developmental Disorders). NIHPublication No. NIH-04-5511, National Institute of Mental Health, National Institutes of Health, U.S.D e p a r t m e n t o f H e a l t h a n d H u m a n S e r v i c e s , B e t h e s d a , M D , 4 0 p p .http://www.nimh.nih.gov/publicat/autism.cfm It may be reproduced or copied without permission fromthe Institute. Citation of the National Institute of Mental Health as the source is appreciated. Reference 2Material in this brochure is in the public domain.

) the (Kaplan & Sadock 8 edn)

Lord C, Bailey A , p 636-663 In Child and AdolescentPsychiatry 4 edn ed Rutter M,Taylor E Blackwelll Scientific Publications ,London 2002

Neurological society guidelines

KanaklataAbbagani ,PhD Thesis 2007 Astudy of Children withAutism and Pasychosocial Interventions

1 Broadstock M, Doughty C, Eggleston M. Systematic review of the effectiveness of pharmacologicaltreatments for adolescents and adults with autism spectrum disorder. Autism. 2007 Jul;11(4):335-48.

2 Chavez B ,Chavez Brown m Rey Ja Role of Risperidone in children with autism Spectrum Disorder AnnPharmacother 2006’40 909 -16.

3 Stachnik JM, Nunn-Thompson C. Use of atypical antipsychotics in the treatment of autistic disorder. AnnPharmacother. 2007Apr;41(4):626-34. Epub 2007 Mar 27. Review

4 4: Smith T, GroenAD, Wynn JW.Randomized trial of intensive early intervention for children with pervasivedevelopmental disorder.Am J Ment Retard. 2000 Jul;105(4):269-85. Erratum in:Am J Ment Retard 2000Nov;105(6):508.Am J Ment Retard 2001 May;106(3):208.PMID: 10934569 [PubMed - indexed for MEDLINE]

5. McConachie H, Diggle T. Parent implemented early intervention for young children with autismspectrumdisorder: a systematic review.J Eval Clin Pract. 2007 Feb;13(1):120-9. Review.

ii) NIH document onAutism

NIH Publication No.04-5511 ,April 2004 andAddendum to the booklet Autism Spectrum DisordersFebruary 2007

iii Chapter on Pervasive Developmental DisordersFred R Volkmar( who was the chief author for the AACAP practice parameters as well ,so updatesto the parameter are from CTPVth edition )

iv) Chapter on Autism Spectrum Disorders

v)v) Pubmed Scan for Randomized Controlled studies in Autism

vi) Department PhD and MD thesis

T Sirisha MD Thesis 2006 A comparative study of Children with Autism and other developmentaldelays

REFERENCES FOR RANDOMISED CONTROLLED STUDIESAND REVIEWS ( PUBMED)

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6. Jesner OS,Aref-Adib M, Coren E. Risperidone for autism spectrum disorder.Cochrane Database Syst Rev. 2007 Jan 24;(1):CD005040. Review.

7. Levy SE, Souders MC, Ittenbach RF, Giarelli E, MulbergAE, Pinto-Martin JA.Relationship of dietary intake to gastrointestinal symptoms in children withautistic spectrum disorders.Biol Psychiatry. 2007 Feb 15;61(4):492-7. Epub 2007 Jan 3.8.Lindsay RL, EugeneArnold L,Aman MG, Vitiello B, Posey DJ, McDougle CJ,Scahill L, Pachler M, McCracken JT, Tierney E, Bozzolo D. Dietary status and impact ofrisperidone on nutritional balance in children with autism: a pilot study.J Intellect DevDisabil. 2006 Dec;31(4):204-9.

9. Tierney E,Aman M, Stout D, Pappas K,Arnold LE, Vitiello B, Scahill L,McDougle C, McCracken J, Wheeler C, MartinA, Posey D, Shah B.Parent satisfaction in a multi-site acute trial of risperidone in children withautism: a social validity study.Psychopharmacology (Berl). 2007 Mar;191(1):149-57.

10. Luby J, Mrakotsky C, Stalets MM, BeldenA, HeffelfingerA, Williams M,Spitznagel E. Risperidone in preschool children with autistic spectrum disorders: aninvestigation of safety and efficacy.J ChildAdolesc Psychopharmacol. 2006 Oct;16(5):575-87.

11. Hollander E, Wasserman S, Swanson EN, Chaplin W, Schapiro ML, Zagursky K,Novotny S.Adouble-blind placebo-controlled pilot study of olanzapine inchildhood/adolescent pervasive developmental disorder.J Child Adolesc Psychopharmacol. 2006Oct;16(5):541-8.

13. DrewA, Baird G, Taylor E, Milne E, Charman T.The Social CommunicationAssessment for Toddlers withAutism (SCATA): aninstrument to measure the frequency, form and function of communication intoddlers with autism spectrum disorder.JAutism Dev Disord. 2007Apr;37(4):648-66.

14. Arnold LE,Aman MG, CookAM, WitwerAN, Hall KL, Thompson S, RamadanY.Atomoxetine for hyperactivity in autism spectrum disorders: placebo-controlledcrossover pilot trial. JAmAcad ChildAdolesc Psychiatry. 2006 Oct;45(10):1196-205.

15. Nagaraj R, Singhi P, Malhi P.Risperidone in children with autism: randomized, placebo-controlled, double-blindstudy.J Child Neurol. 2006 Jun;21(6):450-5.

16. Amminger GP, Berger GE, Schafer MR, Klier C, Friedrich MH, Feucht M.Omega-3 fatty acids supplementation in children with autism: a double-blindrandomized, placebo-controlled pilot study.Biol Psychiatry. 2007 Feb 15;61(4):551-3.Epub 2006Aug 22.

17 Garstang J, Wallis M.Randomized controlled trial of melatonin for children with autistic spectrumdisorders and sleep problems. Child Care Health Dev. 2006 Sep;32(5):585-9.

18 Santosh PJ, Baird G, Pityaratstian N, Tavare E, Gringras P. Impact of comorbid autism spectrum disorderson stimulant response in childrenwith attention deficit hyperactivity disorder: a retrospective andprospective effectiveness study.Child Care Health Dev. 2006 Sep;32(5):575-83.

19 Wigram T, Gold C.

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Music therapy in the assessment and treatment of autistic spectrum disorder:clinical application and research evidence.Child Care Health Dev. 2006 Sep;32(5):535-42. Review.

20. Hollander E, Bartz J, Chaplin W, PhillipsA, Sumner J, Soorya L,AnagnostouE, Wasserman S. Oxytocin increases retention of social cognition in autism.Biol Psychiatry. 2007 Feb 15;61(4):498-503. Epub 2006Aug 14.

21. Smith T, Scahill L, Dawson G, Guthrie D, Lord C, Odom S, Rogers S, WagnerA.Designing research studies on psychosocial interventions in autism.JAutism Dev Disord. 2007 Feb;37(2):354-66. Review.

22. SinhaY, Silove N, Wheeler D, Williams K.Auditory integration training and other sound therapies for autism spectrumdisorders: a systematic review.Arch Dis Child. 2006 Dec;91(12):1018-22. Epub 2006 Aug 3. Review.

23. Anderson GM, Scahill L, McCracken JT, McDougle CJ,Aman MG, Tierney E,ArnoldLE, Martin A, Katsovich L, Posey DJ, Shah B, Vitiello B. Effects of short- and long-term risperidonetreatment on prolactin levels in children with autism.Biol Psychiatry. 2007 Feb 15;61(4):545-50. Epub 2006 May 30.

24. Kasari C, Freeman S, Paparella T. Joint attention and symbolic play in young children with autism: arandomizedcontrolled intervention study.J Child Psychol Psychiatry. 2006 Jun;47(6):611-20.

25. Tonge B, BreretonA, Kiomall M, MackinnonA, King N, Rinehart N.Effects on parental mental health of an education and skills training program forparents of young children with autism: a randomized controlled trial.JAmAcad ChildAdolesc Psychiatry. 2006 May;45(5):561-9.

26. Muskiet FA, Kemperman RF. Folate and long-chain polyunsaturated fatty acids in psychiatric disease.JNutr Biochem. 2006 Nov;17(11):717-27. Epub 2006 May 2.Review.ID: 16650750 [PubMed - indexed for MEDLINE]

27: KolevzonA, Mathewson KA, Hollander E.Selective serotonin reuptake inhibitors in autism: a review of efficacy andtolerability.J Clin Psychiatry. 2006 Mar;67(3):407-14. Review.PMID: 16649827 [PubMed - indexed for MEDLINE]

28: Gold C, Wigram T, Elefant C.Music therapy for autistic spectrum disorder.Cochrane Database Syst Rev. 2006Apr 19;(2):CD004381. Review.PMID: 16625601 [PubMed - indexed for MEDLINE]

29 : Ingersoll B, Gergans S.The effect of a parent-implemented imitation intervention on spontaneousimitation skills in young children with autism.Res Dev Disabil. 2007 Mar-Apr;28(2):163-75. Epub 2006Apr 17.PMID: 16603337 [PubMed - indexed for MEDLINE]

30 : Hellings JA, Zarcone JR, Reese RM, Valdovinos MG, Marquis JG, Fleming KK,Schroeder SR.

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Acrossover study of risperidone in children, adolescents and adults with mentalretardation.JAutism Dev Disord. 2006Apr;36(3):401-11.PMID: 16596465 [PubMed - indexed for MEDLINE]

31: Fisher N, Happe F.Atraining study of theory of mind and executive function in children withautistic spectrum disorders.JAutism Dev Disord. 2005 Dec;35(6):757-71.PMID: 16283087 [PubMed - indexed for MEDLINE]

32: Troost PW, Lahuis BE, Steenhuis MP, Ketelaars CE, Buitelaar JK, van EngelandH, Scahill L, Minderaa RB, Hoekstra PJ.Long-term effects of risperidone in children with autism spectrum disorders: aplacebo discontinuation study.JAmAcad ChildAdolesc Psychiatry. 2005 Nov;44(11):1137-44.PMID: 16239862 [PubMed - indexed for MEDLINE]

33: Nye C, BriceA.Combined vitamin B6-magnesium treatment in autism spectrum disorder.Cochrane Database Syst Rev. 2005 Oct 19;(4):CD003497. Review.PMID: 16235322 [PubMed - indexed for MEDLINE]

34: Pisalchaiyong T, Trairatvorakul C, Jirakijja J,Yuktarnonda W.Comparison of the effectiveness of oral diazepam and midazolam for the sedationof autistic patients during dental treatment.Pediatr Dent. 2005 May-Jun;27(3):198-206.PMID: 16173223 [PubMed - indexed for MEDLINE]

35: Danfors T, von KnorringAL, Hartvig P, Langstrom B, Moulder R, Stromberg B,Torstenson R, Wester U, WatanabeY, Eeg-Olofsson O.Tetrahydrobiopterin in the treatment of children with autistic disorder: adouble-blind placebo-controlled crossover study.J Clin Psychopharmacol. 2005 Oct;25(5):485-9.PMID: 16160627 [PubMed - indexed for MEDLINE]

36: SugieY, Sugie H, Fukuda T, Ito M, SasadaY, Nakabayashi M, Fukashiro K,Ohzeki T.Clinical efficacy of fluvoxamine and functional polymorphism in a serotonintransporter gene on childhood autism.JAutism Dev Disord. 2005 Jun;35(3):377-85.PMID: 16119478 [PubMed - indexed for MEDLINE]

37: Williams KW, Wray JJ, Wheeler DM.Intravenous secretin for autism spectrum disorder.Cochrane Database Syst Rev. 2005 Jul 20;(3):CD003495. Review.PMID: 16034901 [PubMed - indexed for MEDLINE]

38: Research Units on Pediatric PsychopharmacologyAutism Network.Risperidone treatment of autistic disorder: longer-term benefits and blindeddiscontinuation after 6 months.

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Am J Psychiatry. 2005 Jul;162(7):1361-9.PMID: 15994720 [PubMed - indexed for MEDLINE]

39: Ratliff-Schaub K, Carey T, Reeves GD, Rogers MA.Randomized controlled trial of transdermal secretin on behavior of children withautism.Autism. 2005 Jul;9(3):256-65.PMID: 15937041 [PubMed - indexed for MEDLINE]

40: Rana M, Khanzode L, Karnik N, Saxena K, Chang K, Steiner H.Divalproex sodium in the treatment of pediatric psychiatric disorders.Expert Rev Neurother. 2005 Mar;5(2):165-76. Review.PMID: 15853487 [PubMed - indexed for MEDLINE]

41: Hellings JA, Nickel EJ, Weckbaugh M, McCarter K, Mosier M, Schroeder SR.The overt aggression scale for rating aggression in outpatient youth withautistic disorder: preliminary findings.J Neuropsychiatry Clin Neurosci. 2005 Winter;17(1):29-35.PMID: 15746480 [PubMed - indexed for MEDLINE]

42: Hollander E, PhillipsA, Chaplin W, Zagursky K, Novotny S, Wasserman S,Iyengar R.Aplacebo controlled crossover trial of liquid fluoxetine on repetitive behaviorsin childhood and adolescent autism.Neuropsychopharmacology. 2005 Mar;30(3):582-9.PMID: 15602505 [PubMed - indexed for MEDLINE]

43: Sturmey P.Secretin is an ineffective treatment for pervasive developmental disabilities: areview of 15 double-blind randomized controlled trials.Res Dev Disabil. 2005 Jan-Feb;26(1):87-97. Review.PMID: 15590241 [PubMed - indexed for MEDLINE]

44: Sankar R.Initial treatment of epilepsy with antiepileptic drugs: pediatric issues.Neurology. 2004 Nov 23;63(10 Suppl 4):S30-9. Review.PMID: 15557549 [PubMed - indexed for MEDLINE]

45: McElroy SL.Diagnosing and treating comorbid (complicated) bipolar disorder.J Clin Psychiatry. 2004;65 Suppl 15:35-44. Review.PMID: 15554795 [PubMed - indexed for MEDLINE]

46: Thompson WW, DeStefano F, Chen R.Letter to the editor. The safety of thimerosal in newborn and infant vaccines.Vaccine. 2004 Dec 2;23(3):281-2. No abstract available.PMID: 15530668 [PubMed - indexed for MEDLINE]

47: Aldred C, Green J,Adams C.Anew social communication intervention for children with autism: pilotrandomised controlled treatment study suggesting effectiveness.

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J Child Psychol Psychiatry. 2004 Nov;45(8):1420-30.PMID: 15482502 [PubMed - indexed for MEDLINE]

48: MartinA, Scahill L,Anderson GM,Aman M,Arnold LE, McCracken J, McDougleCJ, Tierney E, Chuang S, Vitiello B.Weight and leptin changes among risperidone-treated youths with autism: 6-monthprospective data.Am J Psychiatry. 2004 Jun;161(6):1125-7.PMID: 15169706 [PubMed - indexed for MEDLINE]

49: Millward C, Ferriter M, Calver S, Connell-Jones G.Gluten- and casein-free diets for autistic spectrum disorder.Cochrane Database Syst Rev. 2004;(2):CD003498. Review.PMID: 15106205 [PubMed - indexed for MEDLINE]

50: Sheitman BB, Knable MB, Jarskog LF, Chakos M, Boyce LH, Early J, LiebermanJA.Secretin for refractory schizophrenia.Schizophr Res. 2004 Feb 1;66(2-3):177-81.PMID: 15061251 [PubMed - indexed for MEDLINE]

51: SinhaY, Silove N, Wheeler D, Williams K.Auditory integration training and other sound therapies for autism spectrumdisorders.Cochrane Database Syst Rev. 2004;(1):CD003681. Review.PMID: 14974028 [PubMed - indexed for MEDLINE]

52: McClellan JM, Werry JS.Evidence-based treatments in child and adolescent psychiatry: an inventory.JAmAcad ChildAdolesc Psychiatry. 2003 Dec;42(12):1388-400. Review.PMID: 14627873 [PubMed - indexed for MEDLINE]

53: Lindsay RL,Aman MG.Pharmacologic therapies aid treatment for autism.PediatrAnn. 2003 Oct;32(10):671-6.PMID: 14606217 [PubMed - indexed for MEDLINE]

54: King B, Zwi K, Nunn K, Longworth J, Dossetor D.Use of risperidone in a paediatric population: an observational study.J Paediatr Child Health. 2003 Sep-Oct;39(7):523-7.PMID: 12969207 [PubMed - indexed for MEDLINE]

55: Coplan J, Souders MC, MulbergAE, Belchic JK, Wray J, JawadAF, Gallagher PR,Mitchell R, Gerdes M, Levy SE.Children with autistic spectrum disorders. II: parents are unable to distinguishsecretin from placebo under double-blind conditions.Arch Dis Child. 2003Aug;88(8):737-9.PMID: 12876178 [PubMed - indexed for MEDLINE]

56: Levy SE, Souders MC, Wray J, JawadAF, Gallagher PR, Coplan J, Belchic JK,Gerdes M, Mitchell R, MulbergAE.

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Children with autistic spectrum disorders. I: comparison of placebo and singledose of human synthetic secretin.Arch Dis Child. 2003Aug;88(8):731-6.PMID: 12876177 [PubMed - indexed for MEDLINE]

57: Van Bourgondien ME, Reichle NC, Schopler E.Effects of a model treatment approach on adults with autism.JAutism Dev Disord. 2003Apr;33(2):131-40.PMID: 12757352 [PubMed - indexed for MEDLINE]

58: Bolte S, Feineis-Matthews S, Leber S, Dierks T, Hubl D, Poustka F.The development and evaluation of a computer-based program to test and to teachthe recognition of facial affect.Int J Circumpolar Health. 2002;61 Suppl 2:61-8.PMID: 12585821 [PubMed - indexed for MEDLINE]

59: Molloy CA, Manning-Courtney P, Swayne S, Bean J, Brown JM, Murray DS, KinsmanAM, Brasington M, Ulrich CD 2nd.Lack of benefit of intravenous synthetic human secretin in the treatment ofautism.JAutism Dev Disord. 2002 Dec;32(6):545-51.PMID: 12553591 [PubMed - indexed for MEDLINE]

60: DrewA, Baird G, Baron-Cohen S, CoxA, Slonims V, Wheelwright S, SwettenhamJ, Berry B, Charman T.Apilot randomised control trial of a parent training intervention for pre-schoolchildren with autism. Preliminary findings and methodological challenges.Eur ChildAdolesc Psychiatry. 2002 Dec;11(6):266-72.PMID: 12541005 [PubMed - indexed for MEDLINE]

61: Diggle T, McConachie HR, Randle VR.Parent-mediated early intervention for young children with autism spectrumdisorder.Cochrane Database Syst Rev. 2003;(1):CD003496. Review.PMID: 12535477 [PubMed - indexed for MEDLINE]

63: Niederhofer H, Staffen W, MairA.Galantamine may be effective in treating autistic disorder.BMJ. 2002 Dec 14;325(7377):1422. No abstract available.PMID: 12480867 [PubMed - indexed for MEDLINE]

64: Kasari C.Assessing change in early intervention programs for children with autism.JAutism Dev Disord. 2002 Oct;32(5):447-61. Review.PMID: 12463519 [PubMed - indexed for MEDLINE]

67: Charlop-Christy MH, Carpenter M, Le L, LeBlanc LA, Kellet K.Using the picture exchange communication system (PECS) with children with autism:assessment of PECS acquisition, speech, social-communicative behavior, andproblem behavior.JAppl BehavAnal. 2002 Fall;35(3):213-31.

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