So the diagnosis is autism! So the diagnosis is autism! Now What?…An approach to Now What?…An approach to

the behavioral & medical the behavioral & medical

managementmanagement Dr. R. Garth SmithDr. R. Garth Smith

Developmental Pediatrician &Developmental Pediatrician &Medical DirectorMedical Director

Child Development CentreChild Development CentreHotel Dieu Hospital;Hotel Dieu Hospital;

Associate Professor of Pediatrics Associate Professor of Pediatrics Queen’s UniversityQueen’s University

04/18/2304/18/23

Objectives of This Talk:Objectives of This Talk:

By the end of this talk, you should By the end of this talk, you should appreciate …appreciate …

The widening definition of the The widening definition of the Autistic Spectrum Disorders (ASD’s)Autistic Spectrum Disorders (ASD’s)

The physician’s role in treatment of The physician’s role in treatment of ASD’sASD’sBasic behavioral approachesBasic behavioral approachesRx of co-morbiditiesRx of co-morbidities

Methods Utilized during this Methods Utilized during this sessionsession

Some didactic presentationSome didactic presentation Case presentations (mine and Case presentations (mine and

yours?)yours?) Interactive discussions with Interactive discussions with

questionsquestions

04/18/2304/18/23

Facts about AutismFacts about Autism

Autism is a brain-based disorder, onset prenatalAutism is a brain-based disorder, onset prenatal Involves abnormalities in:Involves abnormalities in:

• Qualitative aspects of social developmentQualitative aspects of social development• Qualitative aspects of communication developmentQualitative aspects of communication development• Repetitive, stereotyped patterns of behavior & Repetitive, stereotyped patterns of behavior &

interestsinterests Affects 4 males to 1 femaleAffects 4 males to 1 female Prevalence for autism is ~1/500; prevalence for Prevalence for autism is ~1/500; prevalence for

ASD is ~1/150ASD is ~1/150

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Autism :an Attempt to Simplify Autism :an Attempt to Simplify the Issuesthe Issues

04/18/2304/18/23

Other Req’ments For AutismOther Req’ments For Autism

Delays/abnormal functioning in at Delays/abnormal functioning in at least 1 of following areas, least 1 of following areas, onset <3 onset <3 yrsyrs

Social interactionSocial interaction Language as used in social Language as used in social

communicationcommunication Symbolic or imaginative playSymbolic or imaginative play Disturbance not due to Rett’s or CDDDisturbance not due to Rett’s or CDD

In children with AutismIn children with Autism As many as :As many as :

• 60% have poor attention/concentration60% have poor attention/concentration• 40% hyperactive40% hyperactive• 88% with unusual preoccupations/rituals88% with unusual preoccupations/rituals• 37% with obsessive thinking37% with obsessive thinking• 89% with stereotyped language89% with stereotyped language• 74% with significant fears/anxiety74% with significant fears/anxiety• 44% with depressed mood, irritability & agitation44% with depressed mood, irritability & agitation• 11% with sleep problems11% with sleep problems• 43% with self-injury43% with self-injury• 10% with tics10% with tics• Seizures in ~14% of autistics with peaks in Infancy & Seizures in ~14% of autistics with peaks in Infancy &

AdolescenceAdolescence• A significant # have feeding & nutritional issuesA significant # have feeding & nutritional issues

Data from Gillberg, 2004

The Problems of Co-morbid The Problems of Co-morbid DiagnosisDiagnosis

DSM-IV somewhat arbitrarily imposes DSM-IV somewhat arbitrarily imposes restrictions, e.g.restrictions, e.g.• Can’t diagnose ADHD & autismCan’t diagnose ADHD & autism• Can’t diagnose OCD & autismCan’t diagnose OCD & autism• Can diagnose Tourette’s & autismCan diagnose Tourette’s & autism

Definitely a problem since clinicians Definitely a problem since clinicians CLEARLY see e.g. ADHD & autism, CLEARLY see e.g. ADHD & autism, etc.etc.

Traits That Vary in ASD’sTraits That Vary in ASD’s

Measured I.Q.

Social Interaction

Communication

Motor Skills

Sensory

Severe delay

Awkward

Uncoordinated

Hypo sensitive

Aloof

Non-verbal

(Gross)

(Fine)

Hypersensitive

Coordinated

Gifted

Active but Odd

Verbal

Agile

Passive

Intellectual Disability

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

Co-morbidities & Co-morbidities & OutcomeOutcome

Cognitive delay (ID/MR)(60% AD; 30% Cognitive delay (ID/MR)(60% AD; 30% ASD) ASD) (Fombonne, 2006)(Fombonne, 2006)

Seizure disorder (Seizure disorder (5% to 44%) 5% to 44%) (Tuchman & (Tuchman & Rapin, 2002: Lancet Neurol)Rapin, 2002: Lancet Neurol)

Depression (Depression (↑ with age) esp with higher ↑ with age) esp with higher functioning individualsfunctioning individuals

Anxiety disorders (all types)Anxiety disorders (all types) Sleep (Sleep (up to 80% of children up to 80% of children

with ASD’s have sleep issues)with ASD’s have sleep issues) Eating/nutritional issuesEating/nutritional issues

Nutrition/Feeding Issues in ASDNutrition/Feeding Issues in ASD

Numerous case studies have reported dietary Numerous case studies have reported dietary selectivity among children with autismselectivity among children with autism

Repetitive behaviors and restricted interests, a Repetitive behaviors and restricted interests, a core feature of autism, may play a role in dietary core feature of autism, may play a role in dietary selectivityselectivity

Children with ASDs often resist novel Children with ASDs often resist novel experiences, which may include tasting new experiences, which may include tasting new foods.foods.

Many children with ASDs have sensory Many children with ASDs have sensory hypersensitivities and may reject foods due to an hypersensitivities and may reject foods due to an aversion to texture, temperature or other aversion to texture, temperature or other characteristics of the foods (e.g appearance).characteristics of the foods (e.g appearance).

Herndon AC et al, 2008

Eating/Dietary IssuesEating/Dietary Issues

Specifically, a study supported previous research Specifically, a study supported previous research that children with autism’s eating behavior is that children with autism’s eating behavior is restricted by restricted by • Food category (Ahearn et al., 2001), Food category (Ahearn et al., 2001), • By texture (Ahearn et al., 2001; Archer & Szatmari, By texture (Ahearn et al., 2001; Archer & Szatmari,

1991), and 1991), and • These children refuse foods more often than typically These children refuse foods more often than typically

developing children (Archer & Szatmari, 1991). developing children (Archer & Szatmari, 1991). Other studies have shown that kids with ASD’s Other studies have shown that kids with ASD’s

are susceptible to a variety of nutritional are susceptible to a variety of nutritional deficiencies! (Arnold et al, 2003, & others)deficiencies! (Arnold et al, 2003, & others)

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

Management OptionsManagement Options

Nutritionist/dietician referral to Nutritionist/dietician referral to evaluate intake adequacyevaluate intake adequacy

Bloodwork (e.g. Ferritin, B12, pre-Bloodwork (e.g. Ferritin, B12, pre-albumen, Zn, etc.)albumen, Zn, etc.)

Referral to feeding team (where Referral to feeding team (where available); OT for “sensory” Rxsavailable); OT for “sensory” Rxs

Sleep Disturbance in AutismSleep Disturbance in Autism

Sleep problems in children with Sleep problems in children with autism autism • prevalence estimates of 44–83% for prevalence estimates of 44–83% for

sleep disorders in this populationsleep disorders in this population• Poor appetite and poor growth were Poor appetite and poor growth were

associated with decreased willingness to associated with decreased willingness to fall asleepfall asleep

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

Sleep Disturbance in AutismSleep Disturbance in Autism

Sleep problems are associated with other Sleep problems are associated with other health conditions and quality of life health conditions and quality of life

Sleep deprivation appears to intensify the Sleep deprivation appears to intensify the behavioral problems of autistic children, behavioral problems of autistic children, improved sleep may improve children’s improved sleep may improve children’s behavior, alleviating maternal stress as a behavior, alleviating maternal stress as a result (personal study)result (personal study)

Decrease in quality sleep could be a source Decrease in quality sleep could be a source of stress that affects not only the child, but of stress that affects not only the child, but also other family members (Richdale, also other family members (Richdale, et al., et al., 2000)2000)

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

Treatment of InsomniaTreatment of Insomnia

The primary approach is so-called “sleep The primary approach is so-called “sleep hygiene” or “behavioral” approaches hygiene” or “behavioral” approaches (establishing routines, allowing to fall (establishing routines, allowing to fall asleep alone, etc)asleep alone, etc)

It is only when these fail that “medical” It is only when these fail that “medical” approaches are entertained. These approaches are entertained. These include…include…• Traditional Medicines, e.g. Trazodone, Traditional Medicines, e.g. Trazodone,

clonidine, etcclonidine, etc• Non-traditional approaches, e.g. Melatonin, Non-traditional approaches, e.g. Melatonin,

tryptophantryptophan

Non-traditional TreatmentsNon-traditional Treatments

Melatonin (MLT) & sleep:Melatonin (MLT) & sleep: 14 kids with “classic autism”were studied14 kids with “classic autism”were studied No autistic patient showed a normal MLT No autistic patient showed a normal MLT

circadian rhythmcircadian rhythm Moreover, autistic children showed Moreover, autistic children showed

significantly lower mean concentrations of significantly lower mean concentrations of MLT, mainly during the dark phase of the MLT, mainly during the dark phase of the day, with respect to the values observed in day, with respect to the values observed in the controlsthe controls

Kulman G et al, 2000

Melatonin in AutisticsMelatonin in Autistics

Melatonin (MLT) & sleep:Melatonin (MLT) & sleep: Jan JE, O'Donnell ME Jan JE, O'Donnell ME (1996)(1996) reviewed reviewed

100 kids with a variety of developmental 100 kids with a variety of developmental disabilities including Autism, disabilities including Autism, • Melatonin, which benefited slightly over 80% of Melatonin, which benefited slightly over 80% of

their patients, appeared to be a safe, their patients, appeared to be a safe, inexpensive, and a very effective treatment of inexpensive, and a very effective treatment of sleep-wake cycle disorderssleep-wake cycle disorders

Our studyOur study

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

?

Non-Pharmacologic Rx’sNon-Pharmacologic Rx’s

May play a role inMay play a role in• Eating/dietary challenges Eating/dietary challenges • Sensory disorders (SID’s) Sensory disorders (SID’s) • Sleeping disorders (some) Sleeping disorders (some) • Some aggressive behaviors Some aggressive behaviors • The general management of ASD’s The general management of ASD’s

Behavior ManagementBehavior Management

Use simple “ABC” approachUse simple “ABC” approach• E.g. may find that transitions create E.g. may find that transitions create

negative behaviorsnegative behaviors• Advanced warning may help reduce Advanced warning may help reduce

these behaviorsthese behaviors• Avoidance of overstimulating (sensory Avoidance of overstimulating (sensory

overload) environments may overload) environments may improvementsimprovements

Sensory DisordersSensory Disorders

Children with ASD’s are particularly Children with ASD’s are particularly susceptible to extremes of sensory susceptible to extremes of sensory vulnerabilitiesvulnerabilities

TactileTactile AuditoryAuditory TasteTaste OlfactoryOlfactory

The Issues in Considering Medical The Issues in Considering Medical Intervention in This Population…Intervention in This Population…

NoNo pharmacologic treatments have pharmacologic treatments have consistentlyconsistently been shown to decrease been shown to decrease core symptoms of…core symptoms of…Social impairment &Social impairment &Communication deficits…common to Communication deficits…common to

autismautism

The Issues in Considering Medical The Issues in Considering Medical Intervention in This Population…Intervention in This Population…

However, there is growing evidence of the However, there is growing evidence of the efficacy of various medications in treating efficacy of various medications in treating “associated symptoms” of autism “associated symptoms” of autism including…including…

Aggression, & agitationAggression, & agitation Hyperactivity, & inattentionHyperactivity, & inattention IrritabilityIrritability Repetitive behaviors & stereotypiesRepetitive behaviors & stereotypies Self-injury &Self-injury & Sleep disordersSleep disorders

Caveats In Treating ASD’sCaveats In Treating ASD’s

The fact that a child meets criteria for The fact that a child meets criteria for autism is autism is notnot a sufficient indication for a sufficient indication for prescribing psycho-pharmacological prescribing psycho-pharmacological agentsagents

Medication may affect physiology and Medication may affect physiology and behavior and may even teach us more behavior and may even teach us more about some of the ‘signs & symptoms’ about some of the ‘signs & symptoms’ shown in autism & other disorders, shown in autism & other disorders, but it but it doesn’t teach the child anything!doesn’t teach the child anything!

Caveats In Treating ASD’sCaveats In Treating ASD’s

It It maymay make the child more receptive make the child more receptive to other educational or general to other educational or general management approaches, but it management approaches, but it doesn’tdoesn’t replace them! replace them!

Caveats In Treating ASD’sCaveats In Treating ASD’s

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

Gringras,P:Practical Paediatric Psychopharmacological prescribing

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

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 What Medications Have Been Looked at In the ASD’sLooked at In the ASD’s

The stimulants e.g. methylphenidate The stimulants e.g. methylphenidate (Ritalin®); Concerta®; Dexedrine®(Ritalin®); Concerta®; Dexedrine®

Atomoxetine (Strattera®)Atomoxetine (Strattera®) 2 2 Adrenergic-agonistsAdrenergic-agonists The antidepressants (SSRI’s and The antidepressants (SSRI’s and

tricyclics)tricyclics) The neuroleptics (antipsychotics)The neuroleptics (antipsychotics)

Typical, e.g. haloperidol (Haldol®)Typical, e.g. haloperidol (Haldol®)Atypical, e.g. risperidone (Risperdal®)Atypical, e.g. risperidone (Risperdal®)

The Psycho-stimulants: Their RoleThe Psycho-stimulants: Their Role

Significant hyperactivity can exist with Significant hyperactivity can exist with autism & Asperger syndrome (10-20%) autism & Asperger syndrome (10-20%) (Ghaziuddin,1998; Martin et al, 1999)(Ghaziuddin,1998; Martin et al, 1999)

These medications act by increasing the These medications act by increasing the neurotransmitters norepinephrine & neurotransmitters norepinephrine & dopamine indirectly in the brain (CNS)dopamine indirectly in the brain (CNS)

For years they were not used in kids with For years they were not used in kids with Autism as it was claimed that they Autism as it was claimed that they increased negativism (including self-increased negativism (including self-injurious behaviors), tics & stereotypiesinjurious behaviors), tics & stereotypies

The Psycho-stimulants: Their RoleThe Psycho-stimulants: Their Role

In 1995, however, Quintana et al In 1995, however, Quintana et al described in an excellent study, that there described in an excellent study, that there was was “… a statistically significant reduction “… a statistically significant reduction in… hyperactivity in… hyperactivity without without an increase in an increase in stereotypic behaviour”, stereotypic behaviour”, using using methylphenidatemethylphenidate

In some kids, adverse effects are seen, In some kids, adverse effects are seen, including including ↑ irritability, paradoxical ↑ in ↑ irritability, paradoxical ↑ in hyperactivity, stereotypic behaviors, or agitationhyperactivity, stereotypic behaviors, or agitation

Aman et al, 2000

The Psycho-stimulants: Their RoleThe Psycho-stimulants: Their Role

Santosh et al (2006) found positive Santosh et al (2006) found positive results in ADHD +autismresults in ADHD +autism

Some kids had Some kids had ↑ obsessionality (use ↑ obsessionality (use lower dosages, and ↑ slowly) (Aman)lower dosages, and ↑ slowly) (Aman)

Santosh et al,2006:

Quintana et al:1995: J of Autism & Developmental Disorders

The Psycho-stimulants: Their RoleThe Psycho-stimulants: Their Role

In higher functioning kids with ASD’s In higher functioning kids with ASD’s response is better, more predictable response is better, more predictable & often low doses are effective& often low doses are effective

In kids with cognitive impairment (IQ In kids with cognitive impairment (IQ <45; mental ages <4.5), success is <45; mental ages <4.5), success is less likely, & idiosyncratic (negative) less likely, & idiosyncratic (negative) responses more likely, responses more likely, including including agitation & stereotypies!agitation & stereotypies!

Hazell P:JPCH, 2007

Hardan A et al,1996; Findling RL et al, 1997, Nicolson R et al,1998, Pandina et al: 2007

The Neuroleptics (Antipsychotics)The Neuroleptics (Antipsychotics)

Atypical Neuroleptics:Atypical Neuroleptics: Risperidone is the most studiedRisperidone is the most studied

These are potent antagonists at serotonin These are potent antagonists at serotonin && dopamine,& have a lower incidence of TD and dopamine,& have a lower incidence of TD and dystoniasdystonias

Improvements noted in … Improvements noted in … irritabilityirritability, , hyperactivity, aggression, repetitive behaviors, hyperactivity, aggression, repetitive behaviors, oppositionality & self-injury (+/- anxiety)oppositionality & self-injury (+/- anxiety)

Weight gain was the most significant side effect Weight gain was the most significant side effect (up to ~16kg)in children; may stabilize over (up to ~16kg)in children; may stabilize over timetime

The Neuroleptics (Antipsychotics)The Neuroleptics (Antipsychotics)

Atypical NeurolepticsAtypical Neuroleptics…continued:…continued: New!New!: RUPP study (2003) recently completed : RUPP study (2003) recently completed

Risperidone was superior to placebo in reducing Risperidone was superior to placebo in reducing symptoms of most concern to parents of autistic symptoms of most concern to parents of autistic children with irritable behavior (2003)children with irritable behavior (2003)

Some evidence of the benefits of risperidone in Some evidence of the benefits of risperidone in irritability, repetition and social withdrawal were irritability, repetition and social withdrawal were apparent (2007)apparent (2007)

Other atypical neuroleptics have been less studied but Other atypical neuroleptics have been less studied but appear no better and olanzapine did not improve appear no better and olanzapine did not improve repetitive behaviorsrepetitive behaviors

Continued efficacy & relative safety noted up to one Continued efficacy & relative safety noted up to one year in a group of autistic kids with risperidoneyear 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.

22--Adrenergic-agonistsAdrenergic-agonists

ClonidineClonidine & & GuanfacineGuanfacine are best studied are best studied ed noradrenergic neurotransmissioned noradrenergic neurotransmission Good study with clonidine Good study with clonidine Improvement Improvement

in hyperactivity, irritability, stereotypes, in hyperactivity, irritability, stereotypes, inappropriate speech & oppositional inappropriate speech & oppositional behavior (only 8 kids used!)behavior (only 8 kids used!)

Was a double-blind, placebo-controlled, Was a double-blind, placebo-controlled, crossover studycrossover study

Adverse effects were: sedation,irritability Adverse effects were: sedation,irritability & hypotension& hypotension

Jaselskis et al, 1992 Guanfacine effective in ~22%: Posey

22--Adrenergic-agonistsAdrenergic-agonists

Lofexidine recently evaluated in a Lofexidine recently evaluated in a small (n=12) but well-done study small (n=12) but well-done study

They used it for kids with autistic They used it for kids with autistic disorder PLUS hyperactivity, disorder PLUS hyperactivity, distractibility and impulsivitydistractibility and impulsivity

Results rated by parents, teachers, Results rated by parents, teachers, and clinicians (viewed videos)and clinicians (viewed videos)

Modest improvement in Modest improvement in onlyonly hyperactivity(without sedation)notedhyperactivity(without sedation)noted

Niederhofer et al, Dec., 2002

The AntidepressantsThe Antidepressants

Tricyclic non-selective serotonin reuptake Tricyclic non-selective serotonin reuptake inhibitor e.g. Clomipramineinhibitor e.g. Clomipramine

In an excellent study by Gordon et al In an excellent study by Gordon et al (1993)this drug was more effective than (1993)this drug was more effective than placebo in treating some symptoms e.g. placebo in treating some symptoms e.g. anger/uncooperativeness, hyperactivity, & anger/uncooperativeness, hyperactivity, & OCD symptomsOCD symptoms

But, side effects of irregular heart rhythm, But, side effects of irregular heart rhythm, lowering of seizure threshold , make it less lowering of seizure threshold , make it less desirable than the SSRI’s desirable than the SSRI’s

SSRI’s in AutismSSRI’s in Autism Fluvoxamine has shown excellent results Fluvoxamine has shown excellent results

in adult autistics with few side in adult autistics with few side effectseffectsdecreased repetitive thoughts & decreased repetitive thoughts & behavior, & maladaptive behavior & behavior, & maladaptive behavior & aggression and improved communicationaggression and improved communication

In children, in contrast, the results were In children, in contrast, the results were not as consistent, esp. in younger kidsnot as consistent, esp. in younger kids

Adverse effects included insomnia, motor Adverse effects included insomnia, motor hyperactivity, agitation, aggression & hyperactivity, agitation, aggression & anxiety (esp. pre-pubertal)anxiety (esp. pre-pubertal)++

+McDougle et al, 2002

SSRI’s in AutismSSRI’s in Autism

Why this difference? Unknown!Why this difference? Unknown! Fluoxetine (Prozac) showed Fluoxetine (Prozac) showed

effectiveness but intolerable side effectiveness but intolerable side effects as above.effects as above.

Sertraline (Zoloft) was useful in 1 Sertraline (Zoloft) was useful in 1 adult study (better with Autism and adult study (better with Autism and PDD-NOS than Asperger syndrome)PDD-NOS than Asperger syndrome)

McDougle, 1998

Defining the repetitive and compulsive Defining the repetitive and compulsive behavior domain in autismbehavior domain in autism

spectrum disorderspectrum disorder A preoccupation with stereotyped A preoccupation with stereotyped

and restricted patterns of interestand restricted patterns of interest Inflexibility in adhering to routines Inflexibility in adhering to routines

and ritualsand rituals Stereotyped and repetitive motor Stereotyped and repetitive motor

mannerismsmannerisms Persistent preoccupation with parts Persistent preoccupation with parts

of objectsof objects

Sertraline’s effectiveness was assessed in Sertraline’s effectiveness was assessed in children in an open-label trialchildren in an open-label trial

Nine children with autism between the Nine children with autism between the ages of 6 and 12 were administered ages of 6 and 12 were administered sertraline for the treatment of transition-sertraline for the treatment of transition-associated anxiety and agitation. associated anxiety and agitation.

It was found that 89% of the subjects had It was found that 89% of the subjects had a positive response.a positive response.

Results suggest the importance of future Results suggest the importance of future controlled investigation of sertraline in controlled investigation of sertraline in pediatric and adult ASD populations.pediatric and adult ASD populations.

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

Citalopram (Celexa) is one of Citalopram (Celexa) is one of the most highly selective SSRIs the most highly selective SSRIs A published open-label, chart-review of citalopram in 15 A published open-label, chart-review of citalopram in 15

children and adolescents who had PDDs suggested children and adolescents who had PDDs suggested • improvements in repetitive behaviors and improvements in repetitive behaviors and • anxiety based on CGI-S and CGI-I ratings [49]. anxiety based on CGI-S and CGI-I ratings [49].

The study reported a mean dose of citalopram was 16.9 mg plus 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 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.over an average period of 218.8 plus or minus 167.2 days.

Of the 15 cases, 11 were much improved or very much Of the 15 cases, 11 were much improved or very much improved. improved. • The longer the subject was on the treatment, the more positive the The longer the subject was on the treatment, the more positive the

response. As noted, anxiety and repetitive behaviors or stereotypies were response. As noted, anxiety and repetitive behaviors or stereotypies were most responsive to citalopram, with 10 of the 15 subjects showing most responsive to citalopram, with 10 of the 15 subjects showing improvement in anxiety, presumably related to reduced rigidity in adherence improvement in anxiety, presumably related to reduced rigidity in adherence to routines and rituals.to routines and rituals.

Although length of treatment time correlated positively with Although length of treatment time correlated positively with response, higher dosages did not. response, higher dosages did not.

Early intervention with selective Early intervention with selective serotonin reuptake inhibitorsserotonin reuptake inhibitors

SSRIs have been presented as a model pharmacologic SSRIs have been presented as a model pharmacologic treatment, because serotonin is known to enhance treatment, because serotonin is known to enhance synapse refinement in the brains of autistic childrensynapse refinement in the brains of autistic children

In the developing cortex, serotonin is concerned with In the developing cortex, serotonin is concerned with maturation of thalamic afferents, cortical dendrites, maturation of thalamic afferents, cortical dendrites, and axons, with alterations in the levels of serotonin and axons, with alterations in the levels of serotonin potentially resulting in negative effects.potentially resulting in negative effects.• High levels of serotonin may reduce pruning of the dendritic High levels of serotonin may reduce pruning of the dendritic

branchesbranches• Too little serotonin causing a smaller number of dendritic Too little serotonin causing a smaller number of dendritic

spines than usual, miniscule dendritic arbors and spines than usual, miniscule dendritic arbors and somatosensory barrels, and a decrease in synaptic densitysomatosensory barrels, and a decrease in synaptic density

Early intervention with selective Early intervention with selective serotonin reuptake inhibitorsserotonin reuptake inhibitors

Interventions targeting normalization of serotonin Interventions targeting normalization of serotonin regulation in the developing brain of young regulation in the developing brain of young children who have autism has been proposed as a children who have autism has been proposed as a novel, early intervention strategynovel, early intervention strategy

A pilot, randomized, placebo-controlled trial is A pilot, randomized, placebo-controlled trial is being funded by the NIH STAART network in being funded by the NIH STAART network in toddlers and preschoolers who have autism to toddlers and preschoolers who have autism to evaluate the effects of liquid fluoxetine on global evaluate the effects of liquid fluoxetine on global improvements and alterations in developmental improvements and alterations in developmental progressions in young children who have ASDs.progressions in young children who have ASDs.

Newer Options in AutismNewer Options in Autism

In light of the recently reported In light of the recently reported neuropathologic and neurochemical neuropathologic and neurochemical abnormalities of the abnormalities of the cholinergic pathways in cholinergic pathways in autism…autism…

Donepezil,Aricept, a cholinesterase inhibitor, is Donepezil,Aricept, a cholinesterase inhibitor, is a potentially useful agent in the treatment of a potentially useful agent in the treatment of cognitive and behavioral symptoms observed cognitive and behavioral symptoms observed in this disorderin this disorder

Eight patients (mean age = 11.0 +/- 4.1 years; Eight patients (mean age = 11.0 +/- 4.1 years; range 7-19 years)were openly treatedrange 7-19 years)were openly treated

Donepezil, AriceptDonepezil, Aricept in Autism in Autism Four of these patients (50%) demonstrated Four of these patients (50%) demonstrated

significant improvement as assessed by the significant improvement as assessed by the Aberrant Behavior Checklist and the Clinical Aberrant Behavior Checklist and the Clinical Global Impression Scale.Global Impression Scale.

Decreases in the Irritability and Hyperactivity Decreases in the Irritability and Hyperactivity subscales were observedsubscales were observed

But no changes in the Inappropriate Speech, But no changes in the Inappropriate Speech, Lethargy, and Stereotypies subscales were Lethargy, and Stereotypies subscales were notednoted

Limited and transient side effects were Limited and transient side effects were reported, with one patient experiencing reported, with one patient experiencing gastrointestinal disturbances and another gastrointestinal disturbances and another reporting mild irritabilityreporting mild irritability