Kaplan + Sadock's Synopsis of Psychiatry, 11e

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31.5 Autism Spectrum Disorder

Complementary and Alternative Medicine (CAM) Approaches to Autism Spectrum Disorder Complementary and alternative medicine (CAM) is a group of nontraditional treatments that are generally used in con- junction with conventional treatments. Safe interventions that have been applied to target both core and associated behav- ioral features of autism spectrum disorder with unknown efficacy include the following: music therapy, to promote communication and expression; and yoga, to promote atten- tion and decrease activity level. A biologically based practice that is deemed safe and shown to be efficacious is melatonin, which is effective in reducing sleep-onset latency in children. Other biological practices that are recognized as safe but with unknown efficacy include vitamin C, multivitamins, essen- tial fatty acids, and the amino acids carnosine and carnitine. Secretin has been shown to be ineffective in RCTs in the treat- ment of autism spectrum disorder. The autistic spectrum covers a range of behaviors which, prior to the change in the DSM-5 were listed separately, and which are now no longer diagnosed as separate entities in the diagnos- tic manual. Nevertheless, the descriptive value of these entities remains important, and it may be some time before the disor- ders described herein disappear from the psychiatric lexicon. In addition, they remain in use in Europe and around the world as useful diagnostic entities and are still coded as separate disor- ders in ICD-10 as discussed. The classification system used in International Classification of Diseases, Tenth Revision (ICD-10) is not congruent with the revisions made in DSM-5 about autistic disorders. ICD-10 still includes separate designations for Rett syndrome, Childhood Disintegrative Disorder, Asperger’s Disorder, and Pervasive Development Disorder Not Otherwise Specified (Table 31.5-4). The authors of Synopsis believe these subtypes to be clini- cally useful, and each is described below. The reader should be aware, however, that according to DSM-5, each is subsumed under the rubric of Autism Spectrum Disorder and should so be diagnosed. Rett Syndrome In 1965, Andreas Rett, an Australian physician, identified a syn- drome in 22 girls who appeared to have developed normally for at least 6 months followed by devastating developmental dete- rioration. Rett syndrome is a progressive condition that has its onset after some months of what appears to be normal develop- ment. Head circumference is normal at birth and developmen- tal milestones are unremarkable in early life. Between 5 and 48 months of age, generally between 6 months and 1 year, head growth begins to decelerate. Disorders Included in Autistic Spectrum Disorder International Classification of Diseases, Tenth Edition (ICD-10)

who are treatment resistant. In studies of its use in adults with schizophrenia, dose ranges of 40 to 160 mg were found to be effective. Adverse effects include sedation, dizziness, and light- headedness. An electrocardiography (ECG) recording is gener- ally obtained before use of this medication. Lithium (Eskalith) has been shown to be efficacious in chil- dren with aggression without autism spectrum disorder, and it is used clinically in the treatment of aggressive or self-injurious behaviors when antipsychotic medications are not effective. Agents Used For Behavioral Impairment In Autism Spectrum Disorder Without Evidence Of Efficacy.  A double-blind study investigated the efficacy of amantadine (Symmetrel), which blocks N -methyl-d-aspartate (NMDA) receptors, in the treatment of behavioral disturbance, such as irritability, aggression, and hyperactivity, in children with autism. Some researchers have suggested that abnormalities of the glutamatergic system may contribute to the emergence of autism spectrum disorders. High glutamate levels have been found in children with the formerly labeled Rett syndrome. In the amantadine study, 47 percent of children on amantadine were rated “improved” by their parents, and 37 percent of children on placebo were rated “improved” by parents in irritability and hyperactivity, although this difference was not statistically sig- nificant. Investigators rated the children on amantadine “signifi- cantly improved” with respect to hyperactivity. A double-blind, placebo-controlled study of the efficacy of the anticonvulsant lamotrigine (Lamictal) on hyperactivity in children with autism showed high rates of placebo improvement in ratings of hyper- activity, which were similar to response on the medication. Clomipramine (Anafranil) has been used in autism spectrum disorder, without RCTs to provide evidence of positive results. Fenfluramine (Pondimin), which reduces blood serotonin levels, has also been used unsuccessfully in the treatment of autism. Improvement does not seem to be associated with a reduction in blood serotonin level. Naltrexone (ReVia), an opioid receptor antagonist, has been investigated without much success, based on the notion that blocking endogenous opioids would reduce autistic symptoms. Tetrahydrobiopterin, a coenzyme that enhances the action of enzymes was used in a double-blind placebo-controlled cross- over study of 12 children with autistic disorder and low con- centrations of spinal tetrahydrobiopterin. The children received a daily dose of 3 mg tetrahydrobiopterin per kilogram during a 6-month period alternating with placebo. Results indicated small, nonsignificant changes in the total scores on the Child- hood Autism Rating Scale after 3- and 6-month treatment. Post hoc analysis of the three core symptoms of autism—social inter- action, communication, and stereotyped behaviors—revealed a significant improvement in social interaction score after 6 months of active treatment. A positive correlation was noted between social response and IQ. These results suggest that there is a possible effect of tetrahydrobiopterin on the social function- ing of children with autism. A recent case report suggested that low-dose venlafax- ine (Effexor) was efficacious in three adolescents and young adults with autistic disorder with self-injurious behavior and hyperactivity. Dose of venlafaxine used was 18.75 mg per day, and efficacy was reported to be sustained over a 6-month period.