Drugs Remain Secondary in Autism Treatment : Psychopharmacologic agents are frequently used but still do not correct the core deficits of the disorder.


BALTIMORE – Psychopharmacologic medications now are often used to alleviate or modify behavior symptoms or comorbid disorders in children with autism, but they do not appear to correct the disorder's core deficits, Scott M. Myers, M.D., said at a meeting on developmental disabilities sponsored by Johns Hopkins University.

The goals of treatment for children with autistic spectrum disorders include maximizing their functional independence and quality of life; promoting their learning, development, and socialization; and alleviating family distress. The reduction of maladaptive behaviors may help to achieve these goals, stressed Dr. Myers, a neurodevelopmental pediatrician at the Geisinger Medical Center in Danville, Pa.

“I think it's important to focus on treating the specific impairments rather than [on] the diagnostic categorization,” he said.

Dr. Myers said he considers using psychopharmacologic medications when behaviors and symptoms interfere with learning and academic performance, socialization, health and safety, and quality of life. Examples of target behaviors include hyperactivity, aggression, self-injury, inattention, mood lability, sleep disturbance, anxiety, and interfering repetitive behaviors.

The Food and Drug Administration has not approved any drug for the treatment of autism in children or adults.

Studies involving more than 2,000 families with an autistic child in North Carolina and Ohio found that about 45%–50% of children with autism were taking psychotropic medication. In these studies, 22% of the children received antidepressants, 15%–17% took antipsychotics, and 11%–14% took stimulants. About 12% of children with autism were taking anticonvulsants (J. Child Adolesc. Psychopharmacol. 2002;12:311–21; J. Autism Dev. Disord. 2003;33:527–34).

But despite their frequent use, medications take a secondary role to educational and behavioral interventions in the treatment of autistic spectrum disorders, he said.

Sometimes medical or environmental factors may cause or exacerbate a behavior or set of behaviors. Pain or discomfort may be the result of an infection, a dental problem, constipation, occult fracture, headache, esophagitis, gastritis, or allergies. Obstructive apnea can interfere with sleep and contribute to daytime behavior problems. Seizures may require treatment, and the medications used to treat them can affect behavior. Iron or zinc deficiency may be a treatable cause of pica.

Awareness of these potential factors will help to direct appropriate therapy, Dr. Myers said. He advises beginning with low doses that are carefully titrated because autistic patients may require very low or very high doses of psychopharmacologic medications, especially the serotonergic agents. Changes in medications or doses should not be made hastily, and only one change in medication should be made at a time.

▸ Selective serotonin reuptake inhibitors (SSRIs). Fluoxetine (Prozac) is the best studied of the SSRIs in children with autistic spectrum disorders, although no double-blind controlled trials have been conducted. In a study of 129 children with autism aged 2–8 years, 17% had an excellent response and 52% had a good response to treatment with fluoxetine at 0.15–0.5 mg/kg for a mean of about 3 years. The highest-functioning children benefited most from fluoxetine, as did those with hyperlexia, a family history of major affective disorder, or a family history of unusual intellectual achievement (Dev. Med. Child Neurol. 2002;44:652–9).

Limited evidence exists for choosing any one specific SSRI over another. Instead, it may be best to consider the drug's half-life and capacity to inhibit cytochrome P450 enzymes. Fluoxetine, sertraline (Zoloft), paroxetine (Paxil), citalopram (Celexa), and escitalopram (Lexapro) are available in liquid form, he added.

Most of the benefits that may occur with SSRI therapy in children with autism are reflected in improved ratings of affect, general behavior, social interaction, rituals, perseveration, stereotypy, and depressive symptoms. SSRIs have been noted to cause adverse reactions in these patients.

▸ Atypical antipsychotics. Two double-blind, placebo-controlled trials have demonstrated positive responses to the atypical antipsychotic risperidone (Risperdal). In these two trials totaling 132 patients, 57%–69% of patients responded positively to risperidone, compared with 6%–12% of placebo patients (Arch. Gen. Psychiatry 1998;55:633–41; N. Engl. J. Med. 2002;347:314–21).

Reports of the use of other atypical antipsychotics–such as olanzapine (Zy-prexa), quetiapine (Seroquel), and ziprasidone (Geodon)–have come from small case series or open-label studies with some success in about half of patients.

▸ α-2 Adrenergic agonists. Very little empirical evidence exists for the use of these agents, which include clonidine (Catapres) and guanfacine (Tenex), in children with autism. Two small (eight and nine patients), double-blind, controlled trials of clonidine each demonstrated modest, short-term improvement in inattention, hyperactivity, impulsivity, and hyperarousal behaviors (J. Clin. Psychopharmacol. 1992;12:322–7; J. Clin. Psychiatry 1992;53:77–82). A retrospective study of guanfacine showed that 24% of 80 patients aged 3–18 years had clinically improved hyperactivity, inattention, and tics (J. Child Adolesc. Psychopharmacol. 2004;14:233–41). Additional research is warranted.


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