31.5 Autism Spectrum Disorder
1163
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.
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.
Disorders Included in Autistic
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.
International Classification of Diseases,
Tenth Edition (ICD-10)
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.
