Effects of risperidone on psychotic symptoms and cognitive functions in 22q11.2 deletion syndrome: Results from a clinical trial

Caren Latrèche, Johanna Maeder, Valentina Mancini, Maude Schneider, Stephan Eliez, Caren Latrèche, Johanna Maeder, Valentina Mancini, Maude Schneider, Stephan Eliez

Abstract

Background: Carriers of the 22q11.2 deletion syndrome (22q11DS) have an enhanced risk of developing psychotic disorders. Full-blown psychosis is typically diagnosed by late adolescence/adulthood. However, cognitive decline is already apparent as early as childhood. Recent findings in mice show that antipsychotic medication administered during adolescence has a long-lasting neuroprotective effect. These findings offer promising evidence for implementing preventive treatment in humans at risk for psychosis.

Methods: We conducted a 12-week double-blind randomized controlled clinical trial with individuals with 22q11DS. Recruitment difficulties resulted in a final sample size of 13 participants (n = 6 treated with antipsychotics and n = 7 receiving placebo). We examined the response to treatment and assessed its short- and long-term effects on psychotic symptomatology using the Structured Interview for Psychosis-Risk Syndromes (SIPS) and cognitive measures.

Results: First, two treated participants discontinued treatment after experiencing adverse events. Second, treated participants showed a short-term improvement in 33.3% of the SIPS items, mainly those targeting negative symptoms. Third, reliable improvements in at least one measure of working memory and attention were respectively found in 83.3 and 66.7% of treated participants.

Conclusion: This is the first double-blind study to investigate the potential neuroprotective effect of antipsychotics in humans at risk for psychosis. Our preliminary results suggest that antipsychotic treatment may prevent long-term deterioration in clinical symptoms and cognitive skills. Yet, given the limited sample size, our findings need to be replicated in larger samples. To do so, future studies may rather adopt open-label or retrospective designs to ensure sufficient power.

Clinical trial registration: [www.ClinicalTrials.gov], identifier [NCT04639960].

Keywords: 22q11 deletion syndrome; antipsychotic treatment; cognition; neuroprotective effect; psychotic disorders.

Conflict of interest statement

Author SE offered Scientific Advice for the Company Servier Laboratory. He also offered invited presentations for TAKEDA, and for Salmon Pharma. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Copyright © 2022 Latrèche, Maeder, Mancini, Schneider and Eliez.

Figures

FIGURE 1
FIGURE 1
CONSORT flow diagram.
FIGURE 2
FIGURE 2
Distribution of side effects by category (in percentages) in the risperidone and the placebo groups.
FIGURE 3
FIGURE 3
Proportion of short-term improvements on each severity subscale (positive, negative, disorganization, and general) of the Structured Interview for Psychosis-Risk Syndromes (SIPS). All (6/6) participants of the risperidone group displayed one improved score in at least one severity scale. In the placebo group, this proportion is 42.86% (3/7 participants).
FIGURE 4
FIGURE 4
Short- and long-term effects treatment on all cognitive measures in the risperidone and placebo groups. Reliable change (i.e., improvements and deteriorations) is achieved if the Reliable Change Index (RCI) exceeds the threshold of ±1.96 (two-tailed 95% confidence interval).

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