Psychopharmacology in Autism Spectrum Disorders

Henry W.M. Kwok

Disclosures

Curr Opin Psychiatry. 2003;16(5) 

In This Article

Abstract and Introduction

Purpose of review: This review is intended to provide an update of recent advances in psychopharmacology to support evidence-based prescription of psychotropic medications for autism spectrum disorders.
Recent Findings: Pharmacotherapy continues to be an important component of a comprehensive treatment program for autism spectrum disorders. Evidence is accumulating supporting the use of second-generation antipsychotic medications and selective serotonin reuptake inhibitors. Recent studies suggest that they are effective and relatively well tolerated, not only in the adult population but also in children with this disorder. Other approaches, such as the use of acetylcholinesterase inhibitors, anticonvulsants and dietary enzymes, may also be potentially useful, but further research on these compounds is needed.
Summary: One of the intriguing aspects of autism spectrum disorders is the unclear pathogenesis. In the absence of any definite evidence of neurochemical abnormalities, there is currently no medication that can be used for the curative treatment of this disorder. However, many distressing symptoms and aberrant behaviors, such as severe tantrums, aggression, hyperactivity and self-injurious behaviors, can be targeted by pharmacotherapy. Amelioration of these symptoms will enhance the individual's ability to participate in educational and community programs, as well as reducing the stress experienced by the carers.

The subject of psychopharmacology in autism spectrum disorders (ASD) is fraught with clinical, methodological and ethical controversies because there are many obstacles to the study of this area. First of all, ASD is a descriptive term that lacks international consensus as to its precise definition. As Brereton and Tonge[1**] have pointed out, for some, ASD refers to a group of different autistic-like conditions - a concept similar to that of pervasive developmental disorders. For others, ASD refers to a unitary concept of autism, conveying the notion of a continuum of severity, from the aloof, intellectually delayed children with 'Kanner-type autism' at one end, to the intelligent and less severely disturbed children with Asperger's disorder at the other end. Therefore it is difficult to compare the findings of different studies and make replications at different centers. In fact, it is not uncommon to see well-designed studies with contradictory findings.

Secondly, the etiology of ASD is still unclear, even though research studies have generated much evidence to suggest that genetic and neurobiological factors play important roles in the pathogenesis. It is not known whether ASD is an entity with a common single cause or instead represents a collection of more or less similar phenotypes with multiple varying etiologies. In their review of the subgroups and boundaries of the autistic spectrum, Willemsen-Swinkels and Buitelaar[2**] remarked that important controversies have not been, and cannot be, resolved as long as no known biological cause or consistent marker has been identified.

Thirdly, there is a lack of good animal models that can be used for hypothesis-driven studies of abnormal behavior development and preclinical testing of novel pharmacological treatments. Recently, Pletnikov et al.[3*] have described a new animal model of ASD that utilizes Borna disease virus to infect the brain of the neonatal rat to produce autistic-like behaviors. Experiments using this animal model may have the potential to provide information on the variability in response to drug treatments.

Finally, another major problem is the difficulty in measuring the effectiveness of medications, because of the paucity of sensitive and validated assessment instruments. Most of the tools are designed to be used for diagnosis rather than for the measurement of a person's progress.[4] The protean manifestation of autism means that these instruments may be too crude to detect subtle but significant changes produced by medications. This is further complicated by the fact that any behavior measurement will inevitably be overshadowed by the natural growth of the child and by the different environmental events that occur in daily life.

Under these circumstances, it is necessary to acknowledge the limitations of the various studies on medical therapies for ASD and to interpret their results with caution. As there is currently no cure for ASD, if medications are used, they should always be part of a comprehensive treatment program that also includes special education, behavioral modification and occupational therapy, as well as training in social and communication skills in a structured and multi-disciplinary setting.

This review highlights new findings and evidence on the subject of psychopharmacology in ASD, evaluating developments in this area published in 2002. A literature search in peer-reviewed journals was conducted from the following sources: MEDLINE, EMBASE, the Cochrane Library and PsycINFO. Studies of both adults and children were included.

Baghdadli et al.[5*] broadly classified psychopharmacological treatment for autistic disorders into three categories. The first includes drugs intended to treat the basic disease process itself, i.e. that which is causing the core signs and symptoms of the disorder. This involves research on substances targeting specific sites or neurochemical pathways. The second category covers drugs used for treatment of troublesome behaviors frequently associated with ASD. The goal is symptomatic relief or alleviation. The third category refers to a wide range of drugs for which only a few case studies exist and for which irregular positive effects are reported.

Research studies on the pathogenesis of ASD conducted in recent years have not been very rewarding, and the neurochemical basis of this disorder remains largely unknown. Although an elevation of whole-blood serotonin is found in more than 30% of patients,[6] the clinical significance of this is unclear. Therefore, at present, there is no well-established pharmacotherapy for targeting the underlying pathophysiological abnormality of ASD. However, there is certainly some evidence to indicate that drugs may be useful in the treatment of various behavioral problems associated with ASD. In the sections below, current research on the different classes of medications is reviewed.

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