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Stimulant treatment effectiveness, safety and risk for psychosis in individuals with 22q11.2 deletion syndrome

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Abstract

This study aimed to retrospectively evaluate an association between stimulant treatment for attention-deficit/hyperactivity disorder (ADHD) in individuals with 22q11.2DS and the development of psychotic disorders, to evaluate long-term effectiveness and safety of stimulant treatment in individuals with 22q11.2DS compared to individuals with idiopathic ADHD, and to explore effects of catechol–O–methyltransferase (COMT) genotype on 22q11.2DS response to stimulants and risk of side effects. Rates of stimulant use and methylphenidate equivalent exposure were compared among individuals with 22q11.2DS, between 51 with psychotic disorders and a control group of 57 22q11.2DS without psychotic disorders, from Tel Aviv and Geneva. In addition, 44 individuals with 22q11.2DS and ADHD from Tel Aviv who initiated stimulants before age 18 years were compared to a control group of 35 age- and sex-matched controls with idiopathic ADHD, for treatment effectiveness (Clinical Global Impression Scale-Improvement), and rates of side effects. Stimulant use history and methylphenidate equivalent exposure did not differ among individuals with 22q11.2DS, between those with and without psychotic disorders. The long-term retrospective follow-up (5.3 ± 4.1 years) of stimulant-treated individuals with 22q11.2DS showed a higher rate of significant clinical improvement of ADHD symptoms, compared to idiopathic ADHD individuals (p = 0.013), and similar side effect rates. There was no effect of the COMT genotype on response to stimulants or on any side effects. This preliminary long-term retrospective analysis suggests that stimulant treatment in 22q11.2DS is apparently safe in terms of psychosis conversion and rates of side effects, and that it is effective in alleviating ADHD symptoms.

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Funding

This study was funded by the Binational Science Foundation (Grant Number 2017369) and by the National Institute for Psychobiology in Israel, Hebrew University of Jerusalem. The ongoing longitudinal study on 22q11DS in Geneva is supported by a grant to Stephan Eliez from the Swiss National Science Foundation (Grant Number: 324730_144260) and by an NCCR grant to Stephan Eliez, Synapsy: The Synaptic Bases of Mental Diseases” (Grant Number: 51NF40-185897). Maude Schneider is supported by an Ambizione grant from the Swiss National Science Foundation (Grant Number: PZ00P1_174206). Role of the sponsors: The funding source had no role in the study design, collection, analysis or interpretation of data, the writing of the article, or the decision to submit the article for publication.

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Author notes

  1. Dana Basel and Mariela Mosheva contributed equally.

Authors and Affiliations

  1. Child Psychiatry Division, Edmond and Lily Safra Children’s Hospital, Sheba Medical Center, 5262000, Tel Hashmoer, Israel

    Dana Basel, Mariela Mosheva, Shachar Shani, Ronnie Weinberger & Doron Gothelf

  2. Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel

    Mariela Mosheva & Doron Gothelf

  3. Developmental Imaging and Psychopathology Lab, Faculty of Medicine, University of Geneva, Geneva, Switzerland

    Johanna Maeder & Stephan Eliez

  4. Clinical Psychology Unit for Intellectual and Developmental Disabilities, Faculty of Psychology and Educational Sciences, University of Geneva, Geneva, Switzerland

    Maude Schneider

  5. Sagol School of Neuroscience, Tel Aviv University, Tel Aviv, Israel

    Doron Gothelf

Authors
  1. Dana Basel
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  2. Mariela Mosheva
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  4. Maude Schneider
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Correspondence to Dana Basel.

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Basel, D., Mosheva, M., Maeder, J. et al. Stimulant treatment effectiveness, safety and risk for psychosis in individuals with 22q11.2 deletion syndrome. Eur Child Adolesc Psychiatry 31, 1367–1375 (2022). https://doi.org/10.1007/s00787-021-01780-z

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  • DOI: https://doi.org/10.1007/s00787-021-01780-z

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