February 2005 • www.eclinicalpsychiatrynews.com Child/Adolescent Psychiatry 39 Drugs Remain Secondary in Treatment

Psychopharmacologic agents are frequently used but Ǡ Selective serotonin reuptake in- Engl. J. Med. 2002;347:314-21). hibitors (SSRIs). (Prozac) is Reports of the use of other atypical an- still do not correct the core deficits of the disorder. the best studied of the SSRIs in children tipsychotics—such as olanzapine (Zy- with autistic spectrum disorders, al- prexa), quetiapine (Seroquel), and ziprasi- BY JEFF EVANS of children with autism were taking psy- though no double-blind controlled trials done (Geodon)—have come from small Senior Writer chotropic medication. In these studies, have been conducted. In a study of 129 case series or open-label studies with some 22% of the children received antidepres- children with autism aged 2-8 years, 17% success in about half of patients. B ALTIMORE — Psychopharmacologic sants, 15%-17% took , and had an excellent response and 52% had a Ǡ α-2 Adrenergic agonists. Very little medications now are often used to allevi- 11%-14% took stimulants. About 12% of good response to treatment with fluoxe- empirical evidence exists for the use of ate or modify behavior symptoms or co- children with autism were taking anti- tine at 0.15-0.5 mg/kg for a mean of these agents, which include (Cat- morbid disorders in children with autism, convulsants (J. Child Adolesc. Psy- about 3 years. The highest-functioning apres) and (Tenex), in children but they do not appear to correct the dis- chopharmacol. 2002;12:311-21; J. Autism children benefited most from fluoxetine, with autism. Two small (eight and nine pa- order’s core deficits, Scott M. Myers, M.D., Dev. Disord. 2003;33:527-34). as did those with hyperlexia, a family his- tients), double-blind, controlled trials of said at a meeting on developmental dis- But despite their frequent use, medica- tory of major affective disorder, or a fam- clonidine each demonstrated modest, abilities sponsored by Johns Hopkins Uni- tions take a secondary role to education- ily history of unusual intellectual achieve- short-term improvement in inattention, versity. al and behavioral in- ment (Dev. Med. hyperactivity, impulsivity, and hyper- The goals of treatment for children with terventions in the Fluoxetine is the best Child Neurol. 2002; arousal behaviors (J. Clin. Psychophar- autistic spectrum disorders include maxi- treatment of autistic 44:652-9). macol. 1992;12:322-7; J. Clin. Psychiatry mizing their functional independence and spectrum disorders, studied of the SSRIs in Limited evidence 1992;53:77-82). A retrospective study of quality of life; promoting their learning, he said. children with autistic exists for choosing guanfacine showed that 24% of 80 patients development, and socialization; and alle- Sometimes med- any one specific SSRI aged 3-18 years had clinically improved hy- viating family distress. The reduction of ical or environmental spectrum disorders, but no over another. Instead, peractivity, inattention, and tics (J. Child maladaptive behaviors may help to achieve factors may cause or double-blind controlled it may be best to con- Adolesc. Psychopharmacol. 2004;14:233- these goals, stressed Dr. Myers, a neu- exacerbate a behavior sider the drug’s half- 41). Additional research is warranted. rodevelopmental pediatrician at the or set of behaviors. trials have been conducted. life and capacity to Ǡ CNS stimulants. has Geisinger Medical Center in Danville, Pa. Pain or discomfort inhibit cytochrome proved to be effective in improving hy- “I think it’s important to focus on treat- may be the result of an infection, a dental P450 enzymes. Fluoxetine, peractivity, impulsivity, and inattention in ing the specific impairments rather than problem, constipation, occult fracture, (Zoloft), (Paxil), citalopram some patients without worsening behav- [on] the diagnostic categorization,” he headache, esophagitis, gastritis, or aller- (Celexa), and escitalopram (Lexapro) are ior or increasing symptoms, such as stereo- said. gies. Obstructive apnea can interfere with available in liquid form, he added. typies or irritability, but such is not the case Dr. Myers said he considers using psy- sleep and contribute to daytime behavior Most of the benefits that may occur for all patients, Dr. Myers said. chopharmacologic medications when be- problems. Seizures may require treatment, with SSRI therapy in children with autism Ǡ Anticonvulsants. In an open-label study haviors and symptoms interfere with and the medications used to treat them can are reflected in improved ratings of affect, of valproic acid, 10 of 14 patients had a sus- learning and academic performance, so- affect behavior. Iron or zinc deficiency general behavior, social interaction, rituals, tained clinical response with decreases in cialization, health and safety, and quality may be a treatable cause of pica. perseveration, stereotypy, and depressive affective instability, impulsivity, aggression, of life. Examples of target behaviors in- Awareness of these potential factors symptoms. SSRIs have been noted to cause and core symptoms. All of the patients clude hyperactivity, aggression, self-injury, will help to direct appropriate therapy, adverse reactions in these patients. who had any electroencephalograph ab- inattention, mood lability, sleep distur- Dr. Myers said. He advises beginning with Ǡ Atypical antipsychotics. Two double- normalities or seizures responded to val- bance, anxiety, and interfering repetitive low doses that are carefully titrated be- blind, placebo-controlled trials have proic acid (J. Clin. Psychiatry 2001;62:530- behaviors. cause autistic patients may require very demonstrated positive responses to the 4). Lamotrigine (Lamictal) did not have The Food and Drug Administration has low or very high doses of psychopharma- atypical any noticeable effects separate from place- not approved any drug for the treatment cologic medications, especially the sero- (Risperdal). In these two trials totaling bo in a double-blind trial of 28 autistic pa- of autism in children or adults. tonergic agents. Changes in medications 132 patients, 57%-69% of patients re- tients, despite some encouraging results in Studies involving more than 2,000 fam- or doses should not be made hastily, and sponded positively to risperidone, com- a previous open-label trial (J. Autism Dev. ilies with an autistic child in North Car- only one change in medication should be pared with 6%-12% of placebo patients Disord. 2001;31:175-81; Neuropediatrics olina and Ohio found that about 45%-50% made at a time. (Arch. Gen. Psychiatry 1998;55:633-41; N. 1994;25:284-9). ■ Link Found Between Maternal Asthma/Allergy and Autism

BY KERRI WACHTER (2,095) were randomly sampled and fre- mothers with autistic children had an al- greater for autistic children who had one Senior Writer quency-matched on birth year, gender, lergic disease, compared with 18% of the or more autistic siblings than for those and birth hospital. control mothers. “Allergic rhinitis was the with healthy siblings. WASHINGTON — Maternal asthma and Maternal disease status was determined particular finding that drove the allergy Maternal autoimmune diseases did not allergic disorders may somehow be linked based on diagnoses in the period 2 years finding,” Dr. Croen said. appear to be associated with a greater risk with disorders, according prior to and 2 years after giving birth. The Whether the mother was diagnosed of autism. Mothers of children in the con- to preliminary research presented at a researchers specifically looked at diag- with asthma or allergy made no difference trol group were just about as likely as meeting of the Centers for Disease Control noses of 44 autoimmune diseases, such as in terms of the child’s risk of autism. mothers of autistic children to have any of and Prevention’s National Center for Birth psoriasis and type 1 diabetes; asthma; and Mothers diagnosed with asthma at any the 44 autoimmune diseases—10% vs. 8%, Defects and Developmental Disabilities. allergic disorders, such as allergic rhinitis, time prior to, during, and after pregnancy, respectively. Mothers of autistic children were more conjunctivitis, atopic eczema, angioede- always had a greater risk of having a child The researchers have postulated sever- likely to have asthma or allergic disorders ma, anaphylaxis, and urticaria. with autism than healthy mothers. Al- al biologic mechanisms for the association. than the mothers of healthy control chil- The group of autistic children was pre- though the same was true for mothers First, it could be because of maternal im- dren in a study of 2,500 children, said Lisa dominantly male (82%). Children in the with allergic disorders, the associations mune response during pregnancy. In par- Croen, Ph.D., a researcher at Kaiser Per- autism group were more likely to be were not as strong. ticular, they hypothesize that maternal manente Northern California, Oakland. twins. Mothers of autistic children were The researchers also looked for associ- antibodies may cross the placenta and dis- Immune function abnormalities have slightly older than the mothers of control ations between medications that mothers rupt fetal neurodevelopment by crossre- been widely reported in association with children. There was a strong association were taking and the frequency of autism acting with fetal brain antigens, through a autism, though the evidence has been between increasing maternal education in the children, to see if this could account process called molecular mimicry. The largely anecdotal. and autism. in part for the association between ma- second hypothesis is that asthma and al- For the study, the researchers identified The researchers found that 16% of the ternal asthma/allergy and autism. They lergy share environmental risk factors 407 children in an outpatient database (for mothers of autistic children were diag- found no correlation between asthma or with autism spectrum disorders. Another Northern California) who were born be- nosed with asthma during the 5-year pe- allergy medication use and an increased possibility is that asthma and allergy share tween January 1995 and June 1999 and riod surrounding their pregnancies, com- frequency of autism. The researchers also genetic susceptibility with autism spec- were diagnosed with an autism spectrum pared with 11% of the mothers of healthy noted that the association between ma- trum disorders—in other words, the dis- disorder. As controls, healthy children children. Likewise, one-quarter of the ternal asthma or allergy and autism was eases share common genes. ■