Pharmacogenomic Characterization of Childbearing-Aged Individuals With Mood Disorders in a Tertiary Care Perinatal Mental Health Clinic.

IF 4.5 2区 医学 Q1 PSYCHIATRY
Jessica L W Mayer, Hannah K Betcher, Laura J Rasmussen-Torvik, Amy Yang, Alfred L George, Tatiana Abramova, Catherine S Stika, Katherine L Wisner, Crystal T Clark, Jacqueline Gollan
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Abstract

Objective: The effectiveness of antidepressant treatment for mood disorders is often limited by either a poor response or the emergence of adverse effects. These complications often necessitate multiple drug trials. This clinical challenge intensifies during pregnancy, when medications must be selected to improve the likelihood of response and optimize reproductive outcomes. We determined the distribution of common pharmacogenetic variants, metabolizer phenotypes, past medication responses, and side effects in childbearing-aged individuals seeking treatment in a tertiary care perinatal mental health clinic.

Methods: Sixty treatment-seeking women (based on sex at birth) with DSM-5- defined bipolar disorder (n = 28) or major depressive disorder (n = 32) provided DNA samples and completed psychiatric diagnostic and severity assessments between April 2014 and December 2017. Samples were genotyped for single-nucleotide variants in drug metabolizing enzyme genes of commonly prescribed antidepressants (cytochrome P450 [CYP] 1A2, 2B6, 2C9, 2C19, 2D6, 3A4, and 3A5), and the frequency of normative metabolizer status was compared to reference populations data from Clinical Pharmacogenetics Implementation Consortium (CPIC) guidelines. The Antidepressant Treatment History Form was used to record historic medication trials and side effects.

Results: A significantly greater proportion of extensive metabolizers for CYP2B6 was observed in the study population when compared to CPIC population frequency databases in Caucasians (0.64 vs 0.43 [95% CI: 0.49-0.76]; P value = .006) and African Americans (0.71 vs 0.33 [95% CI: 0.29-0.96]; P value = .045). No significant association was found between metabolizer phenotype and the likelihood of a medication side effect.

Conclusion: Pharmacogenomic testing may have value for personalized prescribing in individuals capable of or considering pregnancy.

三级护理围产期心理健康门诊中患有情绪障碍的育龄个体的药物基因组特征。
目的:抗抑郁剂治疗情绪障碍的效果往往因反应不佳或出现不良反应而受到限制。这些并发症往往需要进行多次药物试验。这种临床挑战在怀孕期间更为严峻,因为此时必须选择药物来提高反应的可能性并优化生殖结果。我们确定了在一家三级护理围产期精神健康诊所寻求治疗的育龄期患者的常见药物基因变异、代谢表型、既往药物反应和副作用的分布情况:在2014年4月至2017年12月期间,60名患有DSM-5定义的双相情感障碍(n = 28)或重度抑郁障碍(n = 32)的寻求治疗的女性(基于出生时的性别)提供了DNA样本,并完成了精神病诊断和严重程度评估。对样本进行了常用处方抗抑郁药(细胞色素 P450 [CYP] 1A2、2B6、2C9、2C19、2D6、3A4 和 3A5)药物代谢酶基因单核苷酸变异的基因分型,并将正常代谢状态的频率与临床药理遗传学实施联盟(CPIC)指南中的参考人群数据进行了比较。抗抑郁药物治疗史表格用于记录历史用药试验和副作用:结果:与CPIC人群频率数据库相比,研究人群中白种人(0.64 vs 0.43 [95% CI: 0.49-0.76];P值 = .006)和非裔美国人(0.71 vs 0.33 [95% CI: 0.29-0.96];P值 = .045)的CYP2B6广泛代谢者比例明显更高。代谢物表型与药物副作用的可能性之间没有发现明显的关联:药物基因组学检测可能对有怀孕能力或考虑怀孕的人的个性化处方有价值。
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来源期刊
Journal of Clinical Psychiatry
Journal of Clinical Psychiatry 医学-精神病学
CiteScore
7.40
自引率
1.90%
发文量
0
审稿时长
3-8 weeks
期刊介绍: For over 75 years, The Journal of Clinical Psychiatry has been a leading source of peer-reviewed articles offering the latest information on mental health topics to psychiatrists and other medical professionals.The Journal of Clinical Psychiatry is the leading psychiatric resource for clinical information and covers disorders including depression, bipolar disorder, schizophrenia, anxiety, addiction, posttraumatic stress disorder, and attention-deficit/hyperactivity disorder while exploring the newest advances in diagnosis and treatment.
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