Psychopharmacology in Autism Spectrum Disorders

Henry W.M. Kwok


Curr Opin Psychiatry. 2003;16(5) 

In This Article

Other Approaches

A number of recent studies have examined the effects of other drugs on people with ASD.

Acetylcholinesterase inhibitors have been shown to reduce or temporarily stabilize the cognitive impairment in Alzheimer's disease.[43,44,45] They are also reported to reduce psychosis, apathy, disinhibition and aberrant motor behaviors associated with this disease.[46,47,48] It is not known whether there are similar abnormalities in the cholinergic pathways in ASD. Hardan and Handen[49*] reported the results of a retrospective open trial of donepezil, a reversible inhibitor of acetylcholinesterase, on eight children and adolescents (aged 7-19 years) with autistic disorder. Four patients demonstrated significant improvement on the Aberrant Behaviour Checklist and the Clinical Global Impression scale. Decreases in the 'irritability' and 'hyperactivity' scores were observed but there were no changes in the 'inappropriate speech', 'lethargy' or 'stereotypies' subscales. As all the patients in this study were also on concomitant psychoactive medications, further investigations are needed before any conclusion on the benefits of donepezil to ASD can be drawn.

In a review of the biochemical aspects of ASD, Shattock and Whiteley[50**] updated the opioid-excess theory of autism. According to them, the main premise of this theory is that autism is the result of a metabolic disorder. Excessive peptides with opioid activity derived from dietary sources, in particular foods that contain gluten and casein, pass through an abnormally permeable intestinal membrane and enter the central nervous system, exerting an effect on neurotransmission. This theory (also known as the exorphin theory) opens the door to new forms of therapeutic intervention. Instead of imposing dietary restrictions, Brudnak et al.[51*] supplemented the diets of 46 ASD patients aged 5-31 years with a novel dietary enzyme formulation for a period of 12 weeks. Progress was tracked according to the System Outcome Survey. The results showed beneficial effects on all 13 parameters measured, with improvement ranging from 50 to 90%. The authors suggested that further controlled studies are warranted.

Although anticonvulsants are prescribed mainly for epilepsy, the mood-stabilizing and behavioral effects of this class of medication are increasingly being studied. Levetiracetam is an anticonvulsant indicated for adjunctive treatment of partial seizures. Rugino and Samsock[52*] examined the effects of this medication on 10 autistic boys aged 4-10 years. Inattention, hyperkinesis, impulsivity, mood instability and aggression all showed significant improvement. No nootropic effects were observed. The authors concluded that levetiracetam might hold promise for the treatment of autistic children with these problems.

Lastly, in recent years there has been some research interest in the potential role of secretin, a brain-gut peptide hormone, in autism. Horvath et al.[53] reported that it had beneficial effects on the social skills and language development of children with autistic disorder. However, a randomized, double-blind, placebo-controlled trial on 85 children with autism (age 3 to 12 years, mean IQ=55) found no evidence of amelioration of autistic symptoms beyond placebo after a single dose of either biologic or synthetic secretin.[54] A critical review, by Patel et al.[55**], on the effectiveness of secretin suggested that it did not improve autistic symptoms when compared with a placebo. Therefore, it appears that there are insufficient clinical data to support the use of secretin in the treatment of ASD at this stage.


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