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The feasibility and safety of S-adenosyl-l-methionine (SAMe) for the treatment of neuropsychiatric symptoms in 22q11.2 deletion syndrome: a double-blind placebo-controlled trial

  • Biological Child and Adolescent Psychiatry - Original Article
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Abstract

The goal of this trial was to assess the feasibility and safety of using S-adenosyl-l-methionine (SAMe) to treat depressive disorder, attention deficit/hyperactivity disorder (ADHD) and cognitive deficits in individuals with the 22q11.2 deletion syndrome (22q11.2DS). SAMe supposedly enhances the activity of the COMT enzyme. Because individuals with 22q11.2DS have only one copy of the gene responsible for the enzyme, COMT haploinsufficiency may be associated with their psychiatric morbidity and cognitive deficits. We assessed twelve 22q11.2DS individuals with depressive disorder or ADHD in a randomized double-blind cross-over placebo-controlled trial, using SAMe 800 mg bid. Individuals were evaluated for treatment safety and effectiveness during the trial and upon completion at sixth week. Compared to placebo, there were no significant differences in the rate of reported side effects between SAMe and placebo. Despite a general concern that SAMe might induce mania in vulnerable individuals, no manic or psychotic symptoms were exhibited during the SAMe treatment. Individuals with 22q11.2DS with comorbid depressive disorder with or without psychotic symptoms (n = 5) had a larger numerical improvement on relevant clinical scales compared to placebo. No treatment effect was found on ADHD symptoms in subjects who suffered from 22q11.2DS with comorbid ADHD (n = 7). Cognitive performance did not improve or deteriorate following treatment with SAMe compared to placebo. In conclusion SAMe treatment up to 1,600 mg/day for 6 weeks in 22q11.2DS individuals appears to be safe, well tolerated and with no serious side effects. No significant benefit in depressive or ADHD symptoms was detected.

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Acknowledgments

This work was funded by the Basil O’Connor Starter Scholar Research Award of the March of Dimes (Grant No. 5-FY06-590), NARSAD Young Investigator Award and by the Marguerite Stolz Award, Sackler Faculty of Medicine and the Canadian Friends of Tel Aviv University (CFTU). The authors are grateful to Harriet Sugar Miller for editorial assistance and her remarkable support of the project.

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Authors and Affiliations

  1. The Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel

    Tamar Green, Lital Steingart, Amos Frisch & Abraham Weizman

  2. Interdisciplinary Ph.D. Program in Neuroscience, Tel Aviv University, Tel Aviv, Israel

    Omer Zarchi

  3. The Nes-Ziyyona-Beer Yaakov Mental Health Center, Beer Yaakov, Israel

    Tamar Green

  4. The Feinberg Child Study Center, Schneider Children’s Medical Center, Petah Tikva, Israel

    Lital Steingart

  5. The Child Psychiatry Unit, Edmond and Lily Safra Children’s Hospital, Sheba Medical Center, 52621, Tel Hashomer, Israel

    Tamar Green, Lital Steingart, Omer Zarchi & Doron Gothelf

  6. The Felsenstein Medical Research Center, Petah Tikva, Israel

    Amos Frisch & Abraham Weizman

  7. Geha Mental-Health Center, Petah Tikva, Israel

    Abraham Weizman

  8. Sackler Faculty of Medicine and Segol School of Neuroscience, Tel Aviv University, Tel Aviv, Israel

    Doron Gothelf

Authors
  1. Tamar Green
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  2. Lital Steingart
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  3. Amos Frisch
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  4. Omer Zarchi
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  5. Abraham Weizman
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  6. Doron Gothelf
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Corresponding author

Correspondence to Doron Gothelf.

Additional information

T. Green and L. Steingart contributed equally to this work.

The department and institution where the work was done: Behavioral Neurogenetics Center, Schneider Children’s Medical Center of Israel.

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Green, T., Steingart, L., Frisch, A. et al. The feasibility and safety of S-adenosyl-l-methionine (SAMe) for the treatment of neuropsychiatric symptoms in 22q11.2 deletion syndrome: a double-blind placebo-controlled trial. J Neural Transm 119, 1417–1423 (2012). https://doi.org/10.1007/s00702-012-0831-x

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  • DOI: https://doi.org/10.1007/s00702-012-0831-x

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