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.
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.
摘要：
目的：抗抑郁治疗情绪障碍的有效性通常受到反应不良或不良反应出现的限制。这些并发症通常需要多种药物试验。这种临床挑战在怀孕期间加剧，当必须选择药物来提高反应的可能性并优化生殖结果时。我们确定了常见药物遗传学变异的分布，代谢表型，过去的药物反应，以及在三级护理围产期心理健康诊所寻求治疗的育龄患者的副作用。
方法：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）或重度抑郁症（n=32）的寻求治疗的妇女（基于出生时的性别）提供了DNA样本并完成了精神病学诊断和严重程度评估。对常用抗抑郁药（细胞色素P450[CYP]1A2、2B6、2C9、2C19、2D6、3A4和3A5）的药物代谢酶基因中的单核苷酸变体进行基因分型。并且将规范代谢者状态的频率与来自临床药物遗传学实施联盟(CPIC)指南的参考人群数据进行比较。抗抑郁治疗历史表格用于记录历史药物试验和副作用。
结果：与高加索人（0.64vs0.43[95％CI：0.49-0.76];P值=.006）和非裔美国人（0.71vs0.33[95％CI：0.29-0.96];P值=.045）的CPIC人群频率数据库相比，在研究人群中观察到CYP2B6的广泛代谢者比例明显更高。在代谢者表型与药物副作用的可能性之间没有发现显着关联。
结论：药物基因组学测试对于能够或考虑怀孕的个体的个性化处方可能具有价值。
目的：抗抑郁治疗情绪障碍的有效性通常受到反应不良或不良反应出现的限制。这些并发症通常需要多种药物试验。这种临床挑战在怀孕期间加剧，当必须选择药物来提高反应的可能性并优化生殖结果时。我们确定了常见药物遗传学变异的分布，代谢表型，过去的药物反应，以及在三级护理围产期心理健康诊所寻求治疗的育龄患者的副作用。
方法：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）或重度抑郁症（n=32）的寻求治疗的妇女（基于出生时的性别）提供了DNA样本并完成了精神病学诊断和严重程度评估。对常用抗抑郁药（细胞色素P450[CYP]1A2、2B6、2C9、2C19、2D6、3A4和3A5）的药物代谢酶基因中的单核苷酸变体进行基因分型。并且将规范代谢者状态的频率与来自临床药物遗传学实施联盟(CPIC)指南的参考人群数据进行比较。抗抑郁治疗历史表格用于记录历史药物试验和副作用。
结果：与高加索人（0.64vs0.43[95％CI：0.49-0.76];P值=.006）和非裔美国人（0.71vs0.33[95％CI：0.29-0.96];P值=.045）的CPIC人群频率数据库相比，在研究人群中观察到CYP2B6的广泛代谢者比例明显更高。在代谢者表型与药物副作用的可能性之间没有发现显着关联。
结论：药物基因组学测试对于能够或考虑怀孕的个体的个性化处方可能具有价值。
