Genetic, Clinical, and Sociodemographic Factors Associated With Stimulant Treatment Outcomes in ADHD.
Adolescent
Adult
Attention Deficit Disorder with Hyperactivity
/ complications
Central Nervous System Stimulants
/ therapeutic use
Child
Child, Preschool
Comorbidity
Demography
Female
Genome-Wide Association Study
Humans
Male
Mental Disorders
/ complications
Multifactorial Inheritance
Polymorphism, Single Nucleotide
Risk Factors
Social Factors
Treatment Outcome
Young Adult
Attention Deficit Hyperactivity Disorder (ADHD)
Electronic Health Records
Neurodevelopmental Disorders
Pharmacogenetics
Polygenic Risk Scores
Treatment Discontinuation
Journal
The American journal of psychiatry
ISSN: 1535-7228
Titre abrégé: Am J Psychiatry
Pays: United States
ID NLM: 0370512
Informations de publication
Date de publication:
01 09 2021
01 09 2021
Historique:
pubmed:
23
6
2021
medline:
29
9
2021
entrez:
22
6
2021
Statut:
ppublish
Résumé
Stimulant medications are effective for treating attention deficit hyperactivity disorder (ADHD), yet discontinuation and switch to nonstimulant ADHD medications are common. This study aimed to identify genetic, clinical, and sociodemographic factors influencing stimulant treatment initiation, discontinuation, and switch to nonstimulants in individuals with ADHD. The authors obtained genetic and national register data for 9,133 individuals with ADHD from the Danish iPSYCH2012 sample and defined stimulant treatment initiation, discontinuation, and switch from prescriptions. For each stimulant treatment outcome, they examined associations with polygenic risk scores (PRSs) for psychiatric disorders and clinical and sociodemographic factors using survival analyses, and conducted genome-wide association studies (GWASs) and estimated single-nucleotide polymorphism heritability (h Eighty-one percent of the sample initiated stimulant treatment. Within 2 years, 45% discontinued stimulants and 15% switched to nonstimulants. Bipolar disorder PRS (hazard ratio=1.05, 95% CI=1.02, 1.09) and schizophrenia PRS (hazard ratio=1.07, 95% CI=1.03, 1.11) were associated with discontinuation. Depression, bipolar disorder, and schizophrenia PRSs were marginally but not significantly associated with switch (hazard ratio range, 1.05-1.07). No associations were observed for ADHD and autism PRSs. Individuals diagnosed with ADHD at age 13 or older had higher rates of stimulant initiation, discontinuation, and switch (hazard ratio range, 1.27-2.01). Psychiatric comorbidities generally reduced rates of initiation (hazard ratio range, 0.84-0.88) and increased rates of discontinuation (hazard ratio range, 1.19-1.45) and switch (hazard ratio range, 1.40-2.08). h The study findings suggest that individuals with ADHD with higher polygenic liability for mood and/or psychotic disorders, delayed ADHD diagnosis, and psychiatric comorbidities have a higher risk for stimulant treatment discontinuation and switch to nonstimulants. Despite the study's limited sample size, one putative GWAS hit for switch was identified, illustrating the potential of utilizing genomics linked to prescription databases to advance ADHD pharmacogenomics.
Identifiants
pubmed: 34154395
doi: 10.1176/appi.ajp.2020.20121686
pmc: PMC10951468
mid: NIHMS1957352
doi:
Substances chimiques
Central Nervous System Stimulants
0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
854-864Subventions
Organisme : Wellcome Trust
ID : 204895/Z/16/Z
Pays : United Kingdom
Organisme : NIMH NIH HHS
ID : U01 MH109514
Pays : United States
Commentaires et corrections
Type : CommentIn
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