Secretin Treatment for Autistic Disorder: A Critical Analysis

Nick C. Patel, Pharm.D., Jun Y. Yeh, M.S., Marvin D. Shepherd, Ph.D., M. Lynn Crismon, Pharm.D., FCCP

Disclosures

Pharmacotherapy. 2002;22(7) 

In This Article

Abstract and Introduction

We assessed evidence of the effects of secretin on behavior in individuals with autistic disorder. Articles were obtained through a MEDLINE search of the English-language literature from January 1966-November 2001; all investigations and case reports on the topic were included. Press releases obtained from the World Wide Web also were included. Secretin, a gastrointestinal hormone, is suggested to improve autistic symptoms, particularly social function and communication. Two formulations, porcine and synthetic human secretin, were evaluated in humans. A small body of literature and popular belief in autistic disorder communities supported the agent's efficacy. A number of controlled clinical trials did not show improvement in autistic symptoms with secretin compared with placebo, possibly indicating no role for the drug in autistic disorder.

Autistic disorder was first recognized by Kanner in 1943, when he described 11 children with a condition characterized by significant lack of social engagement and problems communicating.[1] These children experienced stereotypies, obsessions, and difficulties with change in routine. At first, the term autistic disorder suggested a childhood form of schizophrenia. During the early 1970s, this was discredited,[2,3] however, and clinicians began to believe that this was in fact a distinct condition, not a continuum of adult schizophrenia. In 1978, Rutter suggested four principal features necessary for the diagnosis: onset before age 30 months; impaired social development not attributable to mental retardation or cognitive delay; impaired language development not attributable to mental retardation or cognitive delay; and unusual behaviors.[4]

The Diagnostic and Statistical Manual of Mental Disorders, 4th edition, text revision (DSM-IV-TR) classifies autistic disorder among the pervasive developmental disorders (PDD).[5] Essential features are "the presence of markedly abnormal or impaired development in social interaction and communication and a markedly restricted repertoire of activity and interests." In addition, there must be delays or abnormal functioning in social interaction, social communication, or symbolic or imaginative play before age 3 years.[5] The full criteria are as follows:

  1. A total of six or more items from I, II, and III, with at least two from I, and one each from II and III:

    1. Qualitative impairment in social interaction, as manifested by at least two of the following:

      1. Marked impairment in the use of multiple nonverbal behaviors such as eye-to-eye gaze, facial expression, body postures, and gestures to regulate social interaction

      2. Failure to develop peer relationships appropriate to developmental level

      3. Lack of spontaneous seeking to share enjoyment, interests, or achievements with other people (lack of showing, bringing, or pointing out object of interest)

      4. Lack of social or emotional reciprocity

    2. Qualitative impairments in communication as manifested by at least one of the following:

      1. Delay in, or total lack of, development of spoken language (not accompanied by an attempt to compensate through alternative modes of communication such as gesture or mime)

      2. In individuals with adequate speech, marked impairment in ability to initiate or sustain conversation with others

      3. Stereotyped and repetitive use of language or idiosyncratic language

      4. Lack of varied, spontaneous make-believe play, or social imitative play appropriate to developmental level

    3. Restricted repetitive and stereotyped patterns of behavior, interests, and activities, as manifested by at least one of the following:

      1. Encompassing preoccupation with one or more stereotyped and restricted patterns of interest that is abnormal either in intensity or focus

      2. Apparently inflexible adherence to specific, nonfunctional routines, or rituals

      3. Stereotyped and repetitive motor mannerisms (hand or finger flapping or twisting, complex whole-body movements)

  2. Delays or abnormal functioning in at least one of the following areas, with onset before age 3 years:

    1. Social interaction

    2. Language as used in social communication

    3. Symbolic or imaginative play

  3. Disturbance not better accounted for by Rett's disorder or childhood disintegrative disorder

Most patients have associated mild-to-profound mental retardation (intelligence quotient [IQ] ≤ 70) and a range of behavioral symptoms, such as hyperactivity, impulsivity, aggressiveness, self-injurious behaviors, or temper tantrums.[5]

The DSM-IV-TR estimates the median prevalence of autistic disorder to be 5/10,000 individuals; epidemiologic studies reported rates of 2-20/10,000 individuals.[5] Studies report increased prevalence, suggesting that between 60,000 and 115,000 children in the United States under 15 years of age fulfill the diagnostic criteria.[6] Possible explanations for increased rates include broader definitions of autism, smaller target populations yielding higher rates, and better screening.[7] Prevalence is 3-5 times greater in boys than in girls.[8]

Autistic disorder usually has onset before age 3 years. It is difficult to make a reliable diagnosis in children younger than 2 years, primarily because manifestations are harder to define in infants. During the child's life, it is not uncommon to see developmental gains during school-age years. Some deteriorate behaviorally during adolescence whereas others seem to improve. Only a small percentage of autistic children are able to live and work independently as adults.[5]

The primary goals of treatment are to improve social response and communication, and to reduce unusual or maladaptive behaviors. Psychotropic agents have played a substantial role since the 1960s. Agents including fenfluramine, haloperidol, naltrexone, psychostimulants, selective serotonin reuptake inhibitors (SSRIs), risperidone, and olanzapine have been examined as potential treatments9; however, their benefits in managing behavior and performance are mediocre. Consequently, alternative therapies have become a focus, such as dimethylglycine, magnesium, and megavitamin B6 supplements.[10] Most recently, the hormone secretin has received a generous amount of attention from researchers, clinicians, the media, and parents of affected children.

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