While the FDA has not approved any medications for the treatment of autism, physicians commonly prescribe a variety of drugs for the management of specific severe symptoms that have not responded to other treatments, such as repetitive self-injurious behaviors. The selection of which medications may be effective for each behavior is made on largely theoretical grounds and based on our understanding of the drugs. For example, I recently talked about the use of Mirtazapine in treating public masturbation among adolescents with Aspergers. Mirtazapine was selected because of its known ability to reduce libido. The study I discussed provided preliminary evidence about its effectiveness.

Antidepressant medications, and especially selective serotonin reuptake inhibitors (SSRIs)  are one of the most common class of drugs used in the treatment of severe autism symptoms, especially repetitive behaviors. The rationale is partly that SSRIs are found effective in treating the type of repetitive behaviors observed in obsessive compulsive disorders. Thus, at least theoretically, SSRIs should be effective in the treatment of repetitive behaviors in autism. Yet, while there is some evidence that these medications work with adults with autism, the evidence for their effectiveness in children is still lacking.

Archives of General Psychiatry, one of the most prestigious scientific journals in our field, just published the findings of a large, multi-site, randomized, double-blinded placebo-controlled study of the effectiveness and safety of citalopram (Celexa) for the treatment of repetitive behaviors in children with autism.  The study included 149 children ages 5 to 17, who had a DSM-IV based diagnosis of autism via the ADOS or ADI.  The children were randomly assigned to receive Celexa or a placebo (which had been matched to the celexa for smell, taste, and viscosity).  The children were then evaluated 12 weeks later with the Clinical Global Impressions- Improvement Scale (CGI-I) and a number of measures designed to examine repetitive behaviors.

The results:

  1. Based on the Clinical Global Impressions Scale, 32% of the children taking Celexa showed a desirable response to the medication. However, 34% of children taking the placebo also showed a similar response. Therefore, the medication was not any more effective than the placebo (“sugar pill”).
  2. The two groups also did not differ on any of the other measures.
  3. Finally, the children taking the medication were more likely than the children taking the placebo to experience/report side effects. The most common of these included increased energy level, impulsiveness, decreased concentration, hyperactivity, stereotypy, diarrhea, insomnia, and dry skin or pruritus.

Below you can see the improvement over time seen in children taking the medication compared to children taking the placebo.

Comparison of improvement in children taking Celexa (black dot) vs. Placebo

The authors concluded that their findings do not support the use of citalopram for the treatment of repetitive behaviors in children with autism.

I want to make another mostly unrelated comment. At the end of the article, as expected, I found the financial disclosures provided by the authors. That is the place where authors state whether they had received funding or salary compensation from organizations, companies, or other institutions that could potentially lead to a conflict of interest. As expected, most of the authors, if not all, reported being associated at some level (consultant, having received funding in the past, etc) with pharmaceutical companies. Why do I bring this up? Because if this study, with the same authors and very solid methodology, had shown that Celexa was effective, many would have dismissed the findings on the basis that the authors were “linked” to big pharma and therefore should not be trusted. Yes, there are a few bad apples that have allowed pharmaceutical companies to affect their ethical judgments, but as a psychologist (not a psychiatrist) working with psychiatrists in research for many years, I have found all researchers to be highly ethical and completely devoted to their science. Yes, limiting links and compensation from pharmaceutical industry would also limit the possibility of conflict of interest, but the presence of such links among academic researchers, does not necessarily mean that the science conducted by these researchers is suspect or not to be trusted.

King, B., Hollander, E., Sikich, L., McCracken, J., Scahill, L., Bregman, J., Donnelly, C., Anagnostou, E., Dukes, K., Sullivan, L., Hirtz, D., Wagner, A., Ritz, L., & , . (2009). Lack of Efficacy of Citalopram in Children With Autism Spectrum Disorders and High Levels of Repetitive Behavior: Citalopram Ineffective in Children With Autism Archives of General Psychiatry, 66 (6), 583-590 DOI: 10.1001/archgenpsychiatry.2009.30
ResearchBlogging.org

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2 Responses to Celexa (citalopram) and autism: Still searching for effective medication management.

  1. RAJ says:

    Nestor;
    You wrote:
    “but the presence of such links among academic researchers, does not necessarily mean that the science conducted by these researchers is suspect or not to be trusted”

    I disagree. There have been many claims of beneficial results of various pharmaceutical treatments for autism based on preliminary results from a single academic researcher.

    The NIH is now funding well designed multi-center clinical trials to verify the claims of academic researchers as you noted in the article.

    One of the authors of the above article, Eric Hollander has been urging the use of Prozac in treating autism in children as young as two years old, based on a study published by Mt. Sinai, where Hollander was the chair of the Dept.of Psychiatry. Hollander has been granted a patent for the use of a derivative of Prozac, under an orphan drug designation, for the use of Prozac in treating autism.

    A multi-center trial found Prozac treatment was no more effective in treating autism than placebo.

    http://www.sciencedaily.com/releases/2009/02/090218135122.htm

    Academic researchers should be held under the same scrutiny as non-academic researchers who promote all sorts of bio-med therapies.

    The history of autism is very appalling when it comes to pharmaceutical treatments of autism.

    Lauretta Bender was considered one of the worlds leading authorities on autism in the 1960′s. She published several studies that found remarkeable improvement after treatment with LSD (before Timothy Leary). Multi center trials by unbiased research groups found no improvement and LSD was dropped as a treatment for autism.

    http://www.neurodiversity.com/library_bender_1962.html

    Edward Ritvo, the former head of UCLA’s autism research group and an editor of the Journal of Autism and Developmental Disorders found remarkeable improvement in autistic children when treated with fenfluromine. Dozens of clinical trials were held throughout the world and found no improvement. After fenfluromine treatment for autism was dropped the FDA eventually banned the use of fenfluromine after it was discovered that fenfluromine was associated with a high risk of heart valve defects.

    http://journals.lww.com/jaacap/Abstract/1983/11000/Effects_of_Fenfluramine_on_14_Outpatients_with_the.6.aspx

    • Hi RAJ, there is no doubt that Psychiatry has had many problems with conflict of interests and the tendency of some clinicians to propose treatments based on a single study before the necessary multi-site research was conducted. But my statement was very specific: that the presence of a link to a pharmaceutical company (for example having served as a consultant in the past, or having received funding) does not mean that their science is not to be trusted. Otherwise, we would simply have to dismiss, as suspect, 90% of published science, not only in psychiatry, but in all of medicine. The alternative to my statement is then that all science conducted by these researchers, regardless of the merits of the methods, is suspect. Under that logic, you would have to dismiss the results of the Celexa study and consider then the possibility that Celexa is actually effective, despite the results of this multi-site study. My general point is that people tend to dismiss some studies as suspect due to conflict of interest ONLY when the results fit their pre-conceived ideas or opinions while simultaneously accepting the results of other studies even when conflict of interests are present.

      I do think that conflict of interests is one factor readers should use when evaluating the merits of a study, but I consider the strength of the science a much more critical and informative factor when determining whether some results should be trusted.
      Nestor.

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