Author/Authors :
Joensen, Beinta Department of Neurobiology Research - Institute of Molecular Medicine - University of Southern Denmark - Odense, Denmark , Meyer, Morten Department of Neurobiology Research - Institute of Molecular Medicine - University of Southern Denmark - Odense, Denmark , Aagaard, Lise Life Science Team - IP and Technology Bech-Bruun Law Firm - Copenhagen, Denmark
Abstract :
T he aim of this study was to review empirical studies examining associations
between candidate genes and adverse events (AEs) from methylphenidate (MPH)
use in children and adolescents. The PubMed, EMBASE, CINAHL, and Web
of Science databases were searched from their inception until March 2017. We
included empirically based articles on pharmacogenetic studies in 0–17‑year‑old
patients that investigated associations between specific candidate genes, their
polymorphisms, and reported AEs. We extracted information about study
design, setting, type of AE reporter, studied genes and their polymorphisms,
age and gender, administered doses, method of genotyping, outcome measures,
and main findings. A total of nine articles reporting information about four
double‑blind, placebo‑controlled, cross‑over studies and five open‑label
cohort studies were eligible for inclusion. Studies were published from 2006
onward and included a total of 998 patients (3–17‑year‑olds) diagnosed with
attention‑deficit hyperactivity disorder (ADHD). Studies predominantly involved
males and lasted from 1 to 12 weeks. Studies used polymerase chain reaction and
single nucleotide polymorphism genotyping methodology. Reported AEs were
significantly associated with the following genes: appetite reduction (CES1*G);
buccal‑lingual movements (T1065G); diastolic blood pressure (ADRA2A
Mspl C/C‑GC); emotionality (DAT1*9/9); irritability (SNAP25 T1065G);
picking (DRD4*7/DRD4*4); social withdrawal (DRD4*7/DRD4*4); somatic
complaints (DAT1*10/10); tics (5‑HTTLRP*S/L*L/L; SNAP25 T1065G);
sadness (CES1*rsl12443580); and vegetative symptoms (5‑HTTLPR). In
conclusion, only few MPH pediatric pharmacogenetic studies were located, and
large between‑study heterogeneity was found. Studies were of naturalistic design
and of short duration. They included small patient samples, poorly standardized
treatment regimens, and limited outcome assessments. In the future, more
pharmacogenomic studies in ADHD are needed, preferably using randomized,
controlled study designs and of longer duration (more than 6 months).
Keywords :
Adverse drug reaction , adverse event , attention‑deficit hyperactivity disorder , Methylphenidate , pediatric , pharmacogenetics
