PMID- 37513866
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20230801
IS  - 1424-8247 (Print)
IS  - 1424-8247 (Electronic)
IS  - 1424-8247 (Linking)
VI  - 16
IP  - 7
DP  - 2023 Jul 3
TI  - CYP2D6 Genotype and Pharmacovigilance Impact on Autism Spectrum Disorder: A 
      Naturalistic Study with Extreme Phenotype Analysis.
LID - 10.3390/ph16070954 [doi]
LID - 954
AB  - The long-term use of psychopharmacology medications in autism spectrum disorder 
      (ASD) hitherto remains controversial due to a lack of evidence about safety and 
      tolerability. In this regard, genotyping the metabolizing enzyme cytochrome P450 
      (CYP) 2D6, especially its extreme phenotypes, could help to prevent drug-related 
      adverse reactions or adverse events (AEs). There are several medications 
      warranting CYP2D6 screening that are consumed by people with ASD, such as 
      risperidone and aripiprazole to name a few. A naturalistic observational study 
      was carried out in participants with ASD to analyze the influence of the CYP2D6 
      phenotype in drug tolerability using a local pharmacovigilance system created for 
      this study. In this case, AEs were identified from participants' electronic 
      health records (EHRs) and paper registries. Other variables were collected: 
      socio-demographic information, comorbidities, and psychopharmacology 
      prescriptions (polypharmacy defined as >/=4 simultaneous prescriptions) and doses. 
      The genetic analysis included allelic discrimination (CYP2D6*1, *2, *3, *4, *5, 
      *6, *10, *17, and *41) and copy number variations. All of these were used to 
      determine theoretical phenotypes of the metabolic profiles: poor (PM); 
      intermediate (IM); normal (NM); and ultra-rapid (UM). Sex differences were 
      analyzed. A total of 71 participants (30 +/- 10 years old, 82% male, 45% CYP2D6 NM 
      phenotype (32 participants)) with a median of 3 (IQR 2-4) comorbidities per 
      person, mainly urinary incontinence (32%) and constipation (22%), were included. 
      CYP2D6 UM showed the highest rate of polypharmacy, whilst, IM participants had 
      the highest rates of neurological and psychiatric AEs, even worse if a CYP2D6 
      inhibitor drug was prescribed simultaneously. CYP2D6 pharmacogenomics and the 
      monitoring of new antipsychotic prescriptions may make a difference in medication 
      safety in adults with ASD. Particularly in those with psychopharmacology 
      polymedication, it can help with AE avoidance and understanding.
FAU - Ballester, Pura
AU  - Ballester P
AUID- ORCID: 0000-0002-7345-448X
AD  - Pharmacology Department, Pharmacy Degree, San Antonio Catholic University, 30107 
      Murcia, Spain.
FAU - Espadas, Cristina
AU  - Espadas C
AD  - Bioengineering Institute, Pediatrics and Organic Chemistry Department, Miguel 
      Hernandez University of Elche (UMH), 03202 Alicante, Spain.
FAU - Almenara, Susana
AU  - Almenara S
AD  - Neuropharmacology on Pain Treatment and Neurodevelopmental Disorders, Dr. Balmis 
      General University Hospital, Alicante Institute for Health and Biomedical 
      Research (ISABIAL), 03010 Alicante, Spain.
AD  - Clinical Pharmacology Unit, Alicante General University Hospital, 03010 Alicante, 
      Spain.
FAU - Barrachina, Jordi
AU  - Barrachina J
AUID- ORCID: 0000-0002-4697-2783
AD  - Neuropharmacology on Pain Treatment and Neurodevelopmental Disorders, Dr. Balmis 
      General University Hospital, Alicante Institute for Health and Biomedical 
      Research (ISABIAL), 03010 Alicante, Spain.
FAU - Muriel, Javier
AU  - Muriel J
AD  - Neuropharmacology on Pain Treatment and Neurodevelopmental Disorders, Dr. Balmis 
      General University Hospital, Alicante Institute for Health and Biomedical 
      Research (ISABIAL), 03010 Alicante, Spain.
AD  - Clinical Pharmacology, Pediatrics and Organic Chemistry Department, Miguel 
      Hernandez University of Elche (UMH), 03202 Alicante, Spain.
FAU - Ramos, Enrique
AU  - Ramos E
AD  - Bioengineering Institute, Pediatrics and Organic Chemistry Department, Miguel 
      Hernandez University of Elche (UMH), 03202 Alicante, Spain.
FAU - Toral, Natalia
AU  - Toral N
AD  - San Rafael Center-San Francisco De Borja Foundation, Residential Facility, 03559 
      Alicante, Spain.
FAU - Belda, Cesar
AU  - Belda C
AD  - Infanta Leonor Center, Autism Parents Association Valencian Community Autism 
      Association (APACV), 03010 Alicante, Spain.
FAU - Peiro, Ana M
AU  - Peiro AM
AUID- ORCID: 0000-0002-2385-3749
AD  - Bioengineering Institute, Pediatrics and Organic Chemistry Department, Miguel 
      Hernandez University of Elche (UMH), 03202 Alicante, Spain.
AD  - Neuropharmacology on Pain Treatment and Neurodevelopmental Disorders, Dr. Balmis 
      General University Hospital, Alicante Institute for Health and Biomedical 
      Research (ISABIAL), 03010 Alicante, Spain.
AD  - Clinical Pharmacology Unit, Alicante General University Hospital, 03010 Alicante, 
      Spain.
AD  - Clinical Pharmacology, Pediatrics and Organic Chemistry Department, Miguel 
      Hernandez University of Elche (UMH), 03202 Alicante, Spain.
LA  - eng
PT  - Journal Article
DEP - 20230703
PL  - Switzerland
TA  - Pharmaceuticals (Basel)
JT  - Pharmaceuticals (Basel, Switzerland)
JID - 101238453
PMC - PMC10385457
OTO - NOTNLM
OT  - CYP2D6
OT  - adverse events
OT  - autism
OT  - pharmacogenetics
OT  - polypharmacy
COIS- All authors declare the absence of any conflicts of interest.
EDAT- 2023/07/29 11:52
MHDA- 2023/07/29 11:53
PMCR- 2023/07/03
CRDT- 2023/07/29 01:38
PHST- 2023/05/18 00:00 [received]
PHST- 2023/06/23 00:00 [revised]
PHST- 2023/06/28 00:00 [accepted]
PHST- 2023/07/29 11:53 [medline]
PHST- 2023/07/29 11:52 [pubmed]
PHST- 2023/07/29 01:38 [entrez]
PHST- 2023/07/03 00:00 [pmc-release]
AID - ph16070954 [pii]
AID - pharmaceuticals-16-00954 [pii]
AID - 10.3390/ph16070954 [doi]
PST - epublish
SO  - Pharmaceuticals (Basel). 2023 Jul 3;16(7):954. doi: 10.3390/ph16070954.