Elsevier

Research in Developmental Disabilities

Volume 26, Issue 1, January–February 2005, Pages 87-97
Research in Developmental Disabilities

Secretin is an ineffective treatment for pervasive developmental disabilities: a review of 15 double-blind randomized controlled trials

https://doi.org/10.1016/j.ridd.2004.09.002Get rights and content

Abstract

In 1998, Horvath et al. [Horvath, K., Stefanatos, G., Sokolski, K. N., Wachtel, R., Nabors, L., & Tildon, J. T. (1998). Improved social and language skills after secretin administration in patients with autism spectrum disorders. Journal of the Association of the Academy of Minority Physicians, 9, 9–15] reported an uncontrolled trial of secretin with three participants with autism, which apparently resulted in significant behavioral improvement. Subsequently, secretin was widely used. Sandler et al. [Sandler, A. D., Sutton, K. A., SeWeese, J., Girardi, M. A., Sheppard, V., & Bodfish, J. W. (1999). Lack of benefit of a single dose of synthetic human secretin in the treatment of autism and pervasive and developmental disorder. The New England Journal of Medicine, 341, 1801–1806] reported the first double-blind trial of secretin with negative results. This article is a review of 15 double-blind trials of secretin. Almost none of the studies reported any significant effects and none concluded that secretin was effective. Transient effects of secretin, including both minor benefits and behavioral deterioration were reported, probably due to multiple statistical tests. Four papers reported data on differential responding in sub-groups of participants, including those with gastrointestinal symptoms. These effects were not replicable. At this time there is no robust evidence that secretin is an effective treatment for pervasive developmental disorders.

Section snippets

Does secretin change behavior of children with PDDs?

All 15 papers reviewed reported no evidence, or almost no evidence, of an effect of secretin on behavior on any measure used. None of the 15 studies concluded that secretin was an effective treatment for autism. All studies used from 1 to 27 dependent variables derived from psychometric instruments. Most used multiple dependent variables while reporting almost no effects. This was true for a very wide range of measures that included core DSM-IV symptoms of PDD's, measures of maladaptive

Response of subgroups of children

It seems reasonable to suppose that, although there may be no overall benefit of secretin, that certain sub-groups of children with PDDs, especially those with GI symptoms, might benefit from secretin. At least four papers tested this hypothesis. Indeed the lack of and specific exclusion of children with GI symptoms might account for the lack of effectiveness reported in some of these trials.

Kern, Van Miller, Evans, and Trivedi (2002) provided the most explicit support for this hypothesis.

Discussion

This review of 15 double-blind, randomized, controlled trials of secretin for autism found almost no evidence for the effectiveness of secretin. It is difficult to prove the null hypothesis that secretin has no effects on the behavior of children with autism; effects may still be found for specific sub-populations, novel or more sensitive dependent variables, with larger samples or with different dosing regimes that have yet to be investigated. Nevertheless, it seems reasonable to conclude that

Acknowledgment

Rinita Laud generously assisted in the editing of this manuscript.

References (21)

  • S.J. Coniglio et al.

    A randomized double-blind, placebo controlled trial of a single dose of intravenous secretin as treatment for children with autism

    The Journal of Pediatrics

    (2001)
  • T. Owley et al.

    Multi-site, double-blind, placebo controlled trial of porcine secretin in autism

    Journal of the American Academy of Child and Adolescent Psychiatry

    (2001)
  • T. Carey et al.

    Double blind placebo controlled trial of secretin Effects on abnormal behavior in children with autism

    Journal of Autism and Developmental Disorders

    (2002)
  • M.G. Chez et al.

    Secretin and autism: A two-part clinical investigation

    Journal of Autism and Developmental Disorders

    (2000)
  • J. Coplan et al.

    Children with autistic spectrum disorders. II: Parents are unable to distinguish secretin from placebo under double-blind conditions

    Archives of the Disease of Childhood

    (2003)
  • B. Corbett et al.

    A double-blind, placebo-controlled crossover study investigating the effect of porcine secretin in children with autism

    Clinical Pediatrics

    (2001)
  • J. Dunn-Geier et al.

    Effect of secretin on children with autism: A randomized controlled trail

    Developmental Medicine and Childhood Neurology

    (2000)
  • W.C. Herlihy

    Letter to the Editor

    The New England Journal of Medicine

    (1999)
  • R.D. Honomichl et al.

    Secretin and sleep in children with autism

    Child Psychiatry, and Human Developmental

    (2002)
  • K. Horvath

    Secretin for autism

    The New England Journal of Medicine

    (1999)
There are more references available in the full text version of this article.

Cited by (45)

  • Repeat-measures longitudinal study evaluating behavioural and gastrointestinal symptoms in children with autism before, during and after visceral osteopathic technique (VOT)

    2016, Journal of Bodywork and Movement Therapies
    Citation Excerpt :

    It was also deemed ethically inappropriate to use a placebo in children with possible learning difficulty/disability. A modified standardised Autism Research Institute – S.O.S questionnaire was used to assess behavioural and gastrointestinal symptoms structured as a 24 parameter grid, with four sub-scales; social behaviour, ritual and repetitive activities, digestive symptoms, and general symptoms (Rimland, 1998; Brudnak et al., 2002; Esch and Carr, 2004; Williams et al., 2005; Erickson et al., 2005; Sturmey, 2005). The study comprised of three periods, Period I – control (baseline), Period II – treatment, and Period III – post-treatment.

  • Complementary and Alternative Medicine Treatments for Children with Autism Spectrum Disorders

    2015, Child and Adolescent Psychiatric Clinics of North America
  • Cumulative complexity: A functional, patient-centered model of patient complexity can improve research and practice

    2012, Journal of Clinical Epidemiology
    Citation Excerpt :

    It also embodies the lost potential of unsuccessful treatments and self-care, which impose workloads but fail to improve symptoms or capacity. This may reflect resistant diseases, inadequate dosing/adherence, or ineffective treatment [154–156], but the consequences are the same: continued, capacity-related vulnerabilities. The cumulative complexity model integrates existing literature into a practical, patient-centered framework.

  • Global hormone profiling of murine placenta reveals Secretin expression

    2011, Placenta
    Citation Excerpt :

    There has been intense interest in the role of Secretin, particularly in the developing brain, following a report that autistic children experienced alleviation of symptoms following Secretin administration [12]. While the effect was not seen in the vast majority of subsequent clinical trials [13–15] one study found an effect among subset of autistic children with GI symptoms [16]. Both the Secretin knockout mouse [17] and the Secretin receptor knockout mouse [18] demonstrate impaired hippocampal synaptic plasticity, whereas the Secretin receptor knockout mice also demonstrated abnormal social and cognitive behaviors [18].

  • Psychopharmacology in autism: An update

    2011, Progress in Neuro-Psychopharmacology and Biological Psychiatry
    Citation Excerpt :

    Anecdotal reports of favorable effects of secretin in children with autism generated strong public opinion and a number of RCT trials had to be performed for more information on its effectiveness. However, none of these trials showed any positive effect on the core symptoms of autism and/or additional behavioral disorders, discouraging the use of secretin in clinical practice (Levy and Hyman, 2008; Sturmey, 2005). Amantidine is an antagonist of the NMDA glutamatergic receptor that has been tested in only one randomized trial.

View all citing articles on Scopus
View full text