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. 2022 May 6;14(5):999.
doi: 10.3390/pharmaceutics14050999.

Pharmacogenetic Interventions Improve the Clinical Outcome of Treatment-Resistant Autistic Spectrum Disorder Sufferers

Maria J Arranz  1   2 , Juliana Salazar  3 , Valentin Bote  4 , Alicia Artigas-Baleri  5 , Alexandre Serra-LLovich  1 , Emma Triviño  6 , Jordi Roige  6 , Carlos Lombardia  6 , Martha Cancino  4 , Marta Hernandez  1   7 , Marc Cendros  1   8 , Enric Duran-Tauleria  9 , Natalia Maraver  9 , Amaia Hervas  4   9
Affiliations

Pharmacogenetic Interventions Improve the Clinical Outcome of Treatment-Resistant Autistic Spectrum Disorder Sufferers

Maria J Arranz et al. Pharmaceutics. .

Abstract

Background: Autistic spectrum disorders (ASD) are severe neurodevelopmental alterations characterised by deficits in social communication and repetitive and restricted behaviours. About a third of patients receive pharmacological treatment for comorbid symptoms. However, 30-50% do not respond adequately and/or present severe and long-lasting side effects.

Methods: Genetic variants in CYP1A2, CYP2C19, CYP2D6 and SLC6A4 were investigated in N = 42 ASD sufferers resistant to pharmacological treatment. Clinical recommendations based on their pharmacogenetic profiles were provided within 24-48 h of receiving a biological sample.

Results: A total of 39 participants (93%) improved after the pharmacogenetic intervention according to their CGI scores (difference in basal-final scores: 2.26, SD 1.55) and 37 participants (88%) according to their CGAS scores (average improvement of 20.29, SD 11.85). Twenty-three of them (55%) achieved symptom stability (CGI ≤ 3 and CGAS improvement ≥ 20 points), requiring less frequent visits to their clinicians and hospital stays. Furthermore, the clinical improvement was higher than that observed in a control group (N = 62) with no pharmacogenetic interventions, in which 66% responded to treatment (difference in CGI scores: -0.87, SD 9.4, p = 1 × 10-5; difference in CGAS scores: 6.59, SD 7.76, p = 5 × 10-8).

Conclusions: The implementation of pharmacogenetic interventions has the potential to significantly improve the clinical outcomes in severe comorbid ASD populations with drug treatment resistance and poor prognosis.

Keywords: ASD; antidepressants; antipsychotics; anxiolytics; personalisation of treatment; pharmacogenetic intervention; pharmacotherapy.

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Conflict of interest statement

Amaia Hervas is a member of the Advisory Board of Exeltis and is conducting clinical trials sponsored by Roche Pharmaceuticals. However, this did not interfere in any way with this study. All the authors declare no conflicts of interest with the contents of this study. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript, or in the decision to publish the results.

Figures

Figure 1
Figure 1
CGI results after pharmacogenetic intervention: (a) final CGI scores; (b) CGI score difference (CGI basal–final).
Figure 2
Figure 2
CGAS results after pharmacogenetic intervention: (a) final CGI scores; (b) CGAS score difference (CGAS final–basal).
See this image and copyright information in PMC

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