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Effect of CYP2D6 genetic variation on patient-reported symptom improvement and side effects among children and adolescents treated with amphetamines.
Gerlach, Samuel; Maruf, Abdullah Al; Shaheen, Sarker M; McCloud, Ryden; Heintz, Madison; McAusland, Laina; Arnold, Paul D; Bousman, Chad A.
Afiliação
  • Gerlach S; Cumming School of Medicine, University of Calgary, Calgary, AB.
  • Maruf AA; College of Pharmacy, Rady Faculty of Health Sciences, University of Manitoba, Winnipeg, MB.
  • Shaheen SM; The Mathison Centre for Mental Health Research and Education, Hotchkiss Brain Institute, Cumming School of Medicine, University of Calgary.
  • McCloud R; Department of Psychiatry, University of Calgary.
  • Heintz M; The Mathison Centre for Mental Health Research and Education, Hotchkiss Brain Institute, Cumming School of Medicine, University of Calgary.
  • McAusland L; Department of Psychiatry, University of Calgary.
  • Arnold PD; The Mathison Centre for Mental Health Research and Education, Hotchkiss Brain Institute, Cumming School of Medicine, University of Calgary.
  • Bousman CA; The Mathison Centre for Mental Health Research and Education, Hotchkiss Brain Institute, Cumming School of Medicine, University of Calgary.
Pharmacogenet Genomics ; 34(5): 149-153, 2024 Jul 01.
Article em En | MEDLINE | ID: mdl-38517706
ABSTRACT

OBJECTIVES:

Amphetamine-based medications are recommended as a first-line pharmacotherapy for the treatment of attention-deficit/hyperactivity disorder in children and adolescents. However, the efficacy and tolerability of these medications vary across individuals, which could be related to interindividual differences in amphetamine metabolism. This study examined if genotype-predicted phenotypes of the cytochrome P450 isozyme CYP2D6 were associated with self-reported side effects and symptom improvement in youth treated with amphetamines.

METHODS:

Two hundred fourteen participants aged 6-24 who had a history of past or current amphetamine treatment were enrolled from Western Canada. Amphetamine dose and duration information was collected from the participants along with questions regarding adherence, concomitant medications, symptom improvement and side effects. DNA was extracted from saliva samples and genotyped for CYP2D6 . Binomial logistic regression models were used to determine the effect of CYP2D6 metabolizer phenotype with and without correction for phenoconversion on self-reported symptom improvement and side effects.

RESULTS:

Genotype-predicted CYP2D6 poor metabolizers had significantly higher odds of reporting symptom improvement when compared to intermediate metabolizers (OR = 3.67, 95% CI = 1.15-11.7, P  = 0.029) after correction for phenoconversion and adjusting for sex, age, dose, duration, and adherence. There was no association between CYP2D6 metabolizer phenotype and self-reported side effects.

CONCLUSION:

Our findings indicate that phenoconverted and genotype-predicted CYP2D6 poor metabolizer phenotype is significantly associated with higher odds of symptom improvement in children and adolescents treated with amphetamine. If replicated, these results could inform the development of future dosing guidelines for amphetamine treatment in children and adolescents.
Assuntos

Texto completo: 1 Bases de dados: MEDLINE Assunto principal: Transtorno do Deficit de Atenção com Hiperatividade / Citocromo P-450 CYP2D6 / Anfetaminas Limite: Adolescent / Adult / Child / Female / Humans / Male Idioma: En Revista: Pharmacogenet Genomics Assunto da revista: FARMACOLOGIA / GENETICA MEDICA Ano de publicação: 2024 Tipo de documento: Article

Texto completo: 1 Bases de dados: MEDLINE Assunto principal: Transtorno do Deficit de Atenção com Hiperatividade / Citocromo P-450 CYP2D6 / Anfetaminas Limite: Adolescent / Adult / Child / Female / Humans / Male Idioma: En Revista: Pharmacogenet Genomics Assunto da revista: FARMACOLOGIA / GENETICA MEDICA Ano de publicação: 2024 Tipo de documento: Article