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

Dana Basel*, Mariela Mosheva, Johanna Maeder, Maude Schneider, Shachar Shani, Ronnie Weinberger, Stephan Eliez, Doron Gothelf

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review


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.

Original languageEnglish
Pages (from-to)1367-1375
Number of pages9
JournalEuropean Child and Adolescent Psychiatry
Issue number9
StatePublished - Sep 2022


FundersFunder number
National Institute for Psychobiology in Israel
United States - Israel Binational Science Foundation
Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen ForschungPZ00P1_174206, 324730_144260
United States-Israel Binational Science Foundation2017369
Hebrew University of Jerusalem


    • 22q11.2 deletion syndrome
    • Psychosis
    • Side effects
    • Stimulants


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