Practice Guidelines

AAP Releases Guidelines on Management of Autism Spectrum Disorders

Am Fam Physician. 2008 Dec 15;78(12):1399-1404.

  This is part 2 of a two-part Practice Guideline on autism spectrum disorders. Part 1, “Identification of Children with Autism Spectrum Disorders,” appeared in the December 1, 2008, issue of AFP.

Guideline source: American Academy of Pediatrics (AAP)

Literature search described? No

Evidence rating system used? No

Published source: Pediatrics, November 2007

Available at: http://pediatrics.aappublications.org/content/vol120/issue5/index.shtml

Autism spectrum disorders (ASDs) affect nearly one of every 150 children and require ongoing medical and nonmedical intervention. ASDs are generally not “curable,” and long-term management is required. The primary goals of treatment are to minimize the core features and associated deficits, maximize functional independence and quality of life, and alleviate family distress. Facilitating development and learning, promoting socialization, reducing maladaptive behaviors, and educating and supporting families can help accomplish these goals.

Optimization of medical care is likely to have a positive impact on habilitative progress and quality of life. In addition to routine preventive care and treatment of acute illnesses, management of sleep dysfunction, coexisting challenging behaviors or psychiatric conditions, and associated medical problems is particularly important. Medications have not been proven to correct the core deficits of ASDs and are not the primary treatment. However, associated maladaptive behaviors or psychiatric comorbidities may interfere with educational progress, socialization, health, safety, and quality of life. These behaviors may be amenable to psychopharmacologic intervention.

Medical Management

Children with ASDs have the same basic health care needs as those without disabilities. They also may have unique health care needs that relate to underlying etiologic conditions (e.g., fragile X syndrome, tuberous sclerosis) or to other conditions often associated with ASDs (e.g., epilepsy).

SEIZURES

The prevalence of epilepsy in persons with ASDs ranges from 11 to 39 percent. Anticonvulsant treatment in children with ASDs is based on the same criteria used for other children with epilepsy, including accurate diagnosis of the seizure type.

Epileptiform abnormalities on electroencephalography (EEG) are common in children with ASDs. Whether subclinical seizures have adverse effects on language, cognition, and behavior is debated, and there is no evidence-based recommendation for the treatment of children with ASDs and epileptiform abnormalities on EEG. Universal screening with EEG in the absence of a clinical indication is not recommended. However, because of the increased prevalence of seizures in children with ASDs, a high index of clinical suspicion should be maintained, and EEG should be considered when there are clinical spells that might represent seizures.

GASTROINTESTINAL PROBLEMS

The relationship between gastrointestinal problems and ASDs is unclear because most studies have not examined representative groups of children with ASDs compared with appropriate control groups. High rates of lymphoid nodular hyperplasia and histologically subtle esophagitis, gastritis, duodenitis, and colitis have been described in children with ASDs who underwent endoscopy. Preliminary evidence suggests that some immunohistochemical features may be unique to inflammation associated with ASDs. Routine specialized gastroenterologic testing is not recommended in asymptomatic children with ASDs. However, if a child with an ASD presents with chronic or recurrent abdominal pain, vomiting, diarrhea, or constipation, it is reasonable to evaluate the gastrointestinal tract. Occult gastrointestinal discomfort also should be considered in a child who presents with a change in behavior, such as outbursts of aggression or self-injury.

SLEEP DISTURBANCE

Sleep problems are common in children and adolescents with ASDs at all levels of cognitive functioning. Sleep problems correlate with family distress and may have significant effects on daytime functioning and quality of life of children with ASDs. In some cases, there may be an identifiable etiology (e.g., obstructive sleep apnea, gastroesophageal reflux). However, when there is not an identifiable medical cause, behavioral interventions including sleep hygiene measures, restriction of daytime sleep, positive bedtime routines, and extinction procedures often are effective.

Little evidence is available regarding pharmacologic management of sleep problems in children with ASDs. Recommendations typically are based on case reports and open-label trials, extrapolation from the adult literature, and expert consensus. There is some evidence of abnormal melatonin regulation in children with ASDs, and melatonin supplementation may improve sleep onset in these patients. Antihistamines, alpha2 agonists, benzodiazepines, chloral hydrate, trazodone (Desyrel; brand no longer available in the United States), and newer nonbenzodiazepine hypnotic agents (e.g., zolpidem [Ambien], zaleplon [Sonata]) sometimes are used to treat insomnia in children. In some cases, other conditions or symptoms such as epilepsy, depression, anxiety, or aggressive outbursts warrant pharmacologic treatment, and an agent that also may assist with sleep can be chosen.

CHALLENGING BEHAVIORS

Problematic emotional reactions and behaviors, such as aggression and self-injury, are common in children and adolescents with ASDs. In some cases, medical factors may cause or exacerbate maladaptive behaviors, and recognition and treatment of medical conditions may eliminate the need for psychopharmacologic agents. When behavioral deterioration in girls is temporally related to menstrual cycles, the use of an analgesic or oral or injectable contraceptive may be helpful. Obstructive sleep apnea may contribute to behavioral deterioration and may be managed with weight reduction, tonsillectomy and adenoidectomy, or continuous positive airway pressure. Pica related to iron or zinc deficiency may respond to mineral supplementation.

It is important to consider environmental factors that may precipitate challenging behaviors. Parents, teachers, or other caregivers may inadvertently reinforce maladaptive behaviors, and in such cases, the most appropriate and effective interventions are behavioral. In some instances, a mismatch between educational or behavioral expectations and the cognitive ability of the child is responsible for disruptive behavior (e.g., when the diagnosis of mental retardation has not been recognized).

Psychopharmacology

Pharmacologic interventions may be considered for maladaptive behaviors, such as aggression, self-injury, repetitive behaviors (e.g., perseveration, obsessions, compulsions, stereotypies), sleep disturbance, mood lability, irritability, anxiety, hyperactivity, inattention, destructive behavior, or other disruptive behaviors (Table 1). After treatable medical causes and modifiable environmental factors have been ruled out, a therapeutic trial of medication may be considered if the behavioral symptoms cause significant impairment in functioning. In some cases, the diagnosis of a comorbid psychiatric disorder can be made, and the patient can be treated with the same medications used in treating these conditions in typically developing children and adolescents.

Table 1

Selected Medication Options for Common Target Symptoms and Comorbidities in Children with Autism Spectrum Disorders

Target symptom Potential comorbidity Selected medication options

Aggression, explosive outbursts, self-injury

Intermittent explosive disorder

Alpha2 agonists (clonidine [Catapres]*, guanfacine [Tenex])

Anticonvulsant mood stabilizers (levetiracetam [Keppra], topiramate [Topamax], valproic acid [Depakene])

Atypical antipsychotic agents (aripiprazole [Abilify], olanzapine [Zyprexa], quetiapine [Seroquel], risperidone [Risperdal]*, ziprasidone [Geodon])

Beta blockers (metoprolol [Toprol], nadolol [Corgard], pindolol, propranolol [Innopran])

SSRIs (citalopram [Celexa], escitalopram [Lexapro], fluoxetine [Prozac]*, fluvoxamine [Luvox]*†, paroxetine [Paxil], sertraline [Zoloft])

Anxiety

Generalized anxiety disorder, anxiety disorder(not otherwise specified)

Buspirone (Buspar)

Mirtazapine (Remeron)

SSRIs (citalopram, escitalopram, fluoxetine*, fluvoxamine*, paroxetine, sertraline)

Bipolar phenotype (behavioral cycling with rages and euphoria, decreased need for sleep, manic-like hyperactivity, irritability, aggression, self-injury, sexual behaviors)

Bipolar I disorder, bipolar disorder (not otherwise specified)

Anticonvulsant mood stabilizers (carbamazepine [Tegretol], gabapentin [Neurontin], lamotrigine [Lamictal], oxcarbazepine [Trileptal], topiramate, valproic acid)

Atypical antipsychotic agents (aripiprazole, olanzapine, quetiapine, risperidone, ziprasidone)

Lithium

Depressive phenotype (marked change from baseline, including symptoms such as social withdrawal, irritability, sadness or crying spells, decreased energy, anorexia, weight loss, sleep dysfunction)

Major depressive disorder, depressive disorder (not otherwise specified)

Mirtazapine

SSRIs (citalopram, escitalopram, fluoxetine*, fluvoxamine*, paroxetine, sertraline)

Hyperactivity, impulsivity, inattention

Attention-deficit/hyperactivity disorder

Alpha2 agonists (clonidine*, guanfacine)

Atomoxetine (Strattera)*

Atypical antipsychotic agents (aripiprazole, olanzapine*, quetiapine, risperidone*, ziprasidone) Stimulants (dextroamphetamine [Dexedrine], methylphenidate [Ritalin]*, mixed amphetamine salts)

Repetitive behavior, behavioral rigidity, obsessive-compulsive symptoms

Obsessive-compulsive disorder, stereotypic movement disorder

Atypical antipsychotic agents (aripiprazole, olanzapine, quetiapine, risperidone*, ziprasidone)

SSRIs (citalopram, escitalopram, fluoxetine*, fluvoxamine*, paroxetine, sertraline)

Valproic acid*

Sleep dysfunction

Circadian rhythm sleep disorder, dyssomnia (not otherwise specified)

Alpha2 agonists (clonidine, guanfacine)

Antihistamines (diphenhydramine [Benadryl], hydroxyzine [Atarax]†)

Benzodiazepines

Chloral hydrate

Melatonin

Mirtazapine

Ramelteon (Rozerem)

Trazodone (Desyrel)†

Zaleplon (Sonata)

Zolpidem (Ambien)


SSRI = selective serotonin reuptake inhibitor.

*— At least one published double-blind, placebo-controlled trial supports use in patients with autism spectrum disorders.

† — Brand no longer available in the United States.

Adapted with permission from Myers SM, Johnson CP, for the American Academy of Pediatrics Council on Children with Disabilities. Management of children with autism spectrum disorders. Pediatrics. 2007;120(5):1169–1170.

Table 1   Selected Medication Options for Common Target Symptoms and Comorbidities in Children with Autism Spectrum Disorders

View Table

Table 1

Selected Medication Options for Common Target Symptoms and Comorbidities in Children with Autism Spectrum Disorders

Target symptom Potential comorbidity Selected medication options

Aggression, explosive outbursts, self-injury

Intermittent explosive disorder

Alpha2 agonists (clonidine [Catapres]*, guanfacine [Tenex])

Anticonvulsant mood stabilizers (levetiracetam [Keppra], topiramate [Topamax], valproic acid [Depakene])

Atypical antipsychotic agents (aripiprazole [Abilify], olanzapine [Zyprexa], quetiapine [Seroquel], risperidone [Risperdal]*, ziprasidone [Geodon])

Beta blockers (metoprolol [Toprol], nadolol [Corgard], pindolol, propranolol [Innopran])

SSRIs (citalopram [Celexa], escitalopram [Lexapro], fluoxetine [Prozac]*, fluvoxamine [Luvox]*†, paroxetine [Paxil], sertraline [Zoloft])

Anxiety

Generalized anxiety disorder, anxiety disorder(not otherwise specified)

Buspirone (Buspar)

Mirtazapine (Remeron)

SSRIs (citalopram, escitalopram, fluoxetine*, fluvoxamine*, paroxetine, sertraline)

Bipolar phenotype (behavioral cycling with rages and euphoria, decreased need for sleep, manic-like hyperactivity, irritability, aggression, self-injury, sexual behaviors)

Bipolar I disorder, bipolar disorder (not otherwise specified)

Anticonvulsant mood stabilizers (carbamazepine [Tegretol], gabapentin [Neurontin], lamotrigine [Lamictal], oxcarbazepine [Trileptal], topiramate, valproic acid)

Atypical antipsychotic agents (aripiprazole, olanzapine, quetiapine, risperidone, ziprasidone)

Lithium

Depressive phenotype (marked change from baseline, including symptoms such as social withdrawal, irritability, sadness or crying spells, decreased energy, anorexia, weight loss, sleep dysfunction)

Major depressive disorder, depressive disorder (not otherwise specified)

Mirtazapine

SSRIs (citalopram, escitalopram, fluoxetine*, fluvoxamine*, paroxetine, sertraline)

Hyperactivity, impulsivity, inattention

Attention-deficit/hyperactivity disorder

Alpha2 agonists (clonidine*, guanfacine)

Atomoxetine (Strattera)*

Atypical antipsychotic agents (aripiprazole, olanzapine*, quetiapine, risperidone*, ziprasidone) Stimulants (dextroamphetamine [Dexedrine], methylphenidate [Ritalin]*, mixed amphetamine salts)

Repetitive behavior, behavioral rigidity, obsessive-compulsive symptoms

Obsessive-compulsive disorder, stereotypic movement disorder

Atypical antipsychotic agents (aripiprazole, olanzapine, quetiapine, risperidone*, ziprasidone)

SSRIs (citalopram, escitalopram, fluoxetine*, fluvoxamine*, paroxetine, sertraline)

Valproic acid*

Sleep dysfunction

Circadian rhythm sleep disorder, dyssomnia (not otherwise specified)

Alpha2 agonists (clonidine, guanfacine)

Antihistamines (diphenhydramine [Benadryl], hydroxyzine [Atarax]†)

Benzodiazepines

Chloral hydrate

Melatonin

Mirtazapine

Ramelteon (Rozerem)

Trazodone (Desyrel)†

Zaleplon (Sonata)

Zolpidem (Ambien)


SSRI = selective serotonin reuptake inhibitor.

*— At least one published double-blind, placebo-controlled trial supports use in patients with autism spectrum disorders.

† — Brand no longer available in the United States.

Adapted with permission from Myers SM, Johnson CP, for the American Academy of Pediatrics Council on Children with Disabilities. Management of children with autism spectrum disorders. Pediatrics. 2007;120(5):1169–1170.

Selective serotonin reuptake inhibitors (SSRIs), atypical antipsychotic agents, stimulants, and alpha2 agonists are the most commonly prescribed psychotropic medications in children with ASDs. Double-blind, placebo-controlled trials have shown that the SSRIs fluoxetine (Prozac) and fluvoxamine (Luvox; brand no longer available in the United States) are effective in the treatment of repetitive and other maladaptive behaviors in patients with ASDs. Open-label trials of these and other SSRIs have shown improvements in target symptoms, including repetitive behaviors, irritability, depressive symptoms, tantrums, anxiety, aggression, difficulty with transitions, social interaction, and language.

Risperidone (Risperdal) is the first medication approved by the U.S. Food and Drug Administration for the symptomatic treatment of irritability (including aggressive behavior, deliberate self-injury, and temper tantrums) in children and adolescents with ASDs. Potential adverse effects include excessive appetite and weight gain, insulin resistance, dyslipidemia, hyperprolactinemia, extrapyramidal symptoms, tardive dyskinesia, neuroleptic malignant syndrome, QTc prolongation, dry mouth, urinary retention, constipation, seizures, hematologic abnormalities, and sedation.

Recent double-blind, placebo-controlled trials of methylphenidate (Ritalin) have shown improvement in hyperactivity, impulsivity, and inattention in children with ASDs. Methylphenidate is effective in some children with ASDs, but the response rate is lower than that in children with isolated attention-deficit/hyperactivity disorder, and adverse effects are more common. It is unclear whether the results can be generalized to other stimulants. Potential adverse effects include appetite reduction, inhibition of growth, delayed sleep onset, jitteriness, exacerbation of tics, abdominal discomfort, increased blood pressure, increased heart rate, irritability, increased anxiety, and repetitive behaviors.

Two small double-blind, placebo-controlled trials have shown modest benefits of clonidine (Catapres) in reducing hyperarousal symptoms (e.g., hyperactivity, irritability and outbursts, impulsivity, repetitive behaviors) in children with ASDs. A prospective open-label trial and a retrospective record review suggest that guanfacine (Tenex) is similarly effective in some patients. Potential adverse effects of these alpha2 agonists include drowsiness, sedation, dry mouth, decreased blood pressure, dizziness, constipation, and irritability.

Complementary and Alternative Medicine

The use of complementary and alternative medicine (CAM) is common in children with ASDs. By the time children receive a formal diagnostic evaluation for a suspected ASD, nearly one third already have tried a complementary or alternative therapy. It is important that health care professionals understand how to evaluate the evidence used to support all treatments, including CAM, psychopharmacologic, and other interventions. Ideally, the evidence supporting or refuting a treatment should include peer-reviewed studies with appropriately diagnosed, well-defined homogeneous study populations; a randomized, double-blind, placebo-controlled design; and an adequate sample size to support the statistical analysis presented. It should also control for confounding factors and use appropriate, validated outcome measures. When evaluating the effectiveness of studies, it is particularly important to keep in mind confounding factors, such as the placebo effect, and the natural history of the disorder.

CAM therapies used to treat ASDs have been categorized as biologic or nonbiologic. Examples of biologic therapies include immunoregulatory interventions (e.g., dietary restriction of food allergens, administration of immunoglobulin or antiviral agents), detoxification therapies (e.g., chelation), gastrointestinal treatments (e.g., digestive enzymes, antifungal agents, probiotics, “yeast-free diet,” gluten/casein-free diet), and dietary supplement regimens (e.g., vitamin A, vitamin C, vitamin B6 and magnesium, folic acid, folinic acid, vitamin B12, dimethylglycine and trimethylglycine, carnosine, omega-3 fatty acids, inositol, various minerals). Examples of nonbiologic interventions include auditory integration training, behavioral optometry, craniosacral manipulation, dolphin-assisted therapy, music therapy, and facilitated communication.

Because of methodologic flaws, insufficient numbers of patients, or lack of replication, many CAM therapies have been inadequately evaluated; therefore, evidence-based recommendations for their use are not possible. The most recent and most appropriately designed trials have demonstrated no significant benefit of dimethylglycine, vitamin B6 and magnesium, or auditory integration training. Positive and negative results have been described for small, methodologically flawed studies of intravenous immunoglobulin. A recent double-blind, placebo-controlled trial revealed no statistically significant differences on Aberrant Behavior Checklist sub-scale scores between small groups of children with ASDs who were given omega-3 fatty acids and those who were given placebo. However, the investigators noted a trend toward superiority of omega-3 fatty acids over placebo for hyperactivity, which suggests that further investigation may be warranted. Although use of the gluten/casein-free diet for children with ASDs is popular, there is little evidence to support or refute this intervention.

Parents of children with ASDs will understandably pursue interventions that they believe may help their child, particularly if the therapies are viewed as being unlikely to have any adverse effects. Unfortunately, families are often exposed to unsubstantiated, pseudoscientific theories and related clinical practices that are, at best, ineffective and, at worst, compete with validated treatments or lead to physical, emotional, or financial harm. Health care professionals can help parents and other caregivers distinguish empirically validated treatment approaches from unproven or ineffective treatments.

Coverage of guidelines from other organizations does not imply endorsement by AFP or the AAFP.


Copyright © 2008 by the American Academy of Family Physicians.
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