Institute of Living/Hartford Healthcare, and the University of Connecticut School of Medicine, Hartford.
Cincinnati Children's Hospital Medical Cent and the College of Medicine at the University of Cincinnati, Ohio.
J Am Acad Child Adolesc Psychiatry. 2022 Jan;61(1):29-31. doi: 10.1016/j.jaac.2021.11.001. Epub 2021 Nov 10.
The role of pharmacogenetics in guiding psychopharmacologic treatment for children and adolescents remains elusive for many clinicians. In the absence of a solid and comprehensive evidence base, sufficient training, education, and consensus guidelines, commercial promotion of pharmacogenetic testing panels has the potential to become the main source of information for providers. Commonly, these tests include multigene panels and group medications into color-coded bins. These panels include both pharmacokinetic (PK) and pharmacodynamic (PD) genes and, using combinatorial algorithms, direct clinicians to use medications "as directed" or caution that "moderate gene-drug interaction(s)" or "significant gene-drug interaction(s)" may exist. Many industry-sponsored studies in adults have concluded that that when clinicians select medications based on pharmacogenomic guidance, patients have better outcomes, although some caution against this approach. To provide evidence on the clinical impact and potential of pharmacogenetic testing panels in clinical practice in child and adolescent psychiatry, in this issue of the Journal, Vande Voort and colleagues report the results of a prospective trial of pharmacogenetically guided treatment versus treatment as usual in depressed adolescents. The authors randomized adolescents aged 13 to 18 years with moderate to severe major depressive disorder (N = 176) to treatment guided by combinatorial pharmacogenetic testing that was either available at the baseline visit (GENE arm, n = 84) or at the 8-week visit (treatment-as-usual arm, n = 92). Patients and raters were blinded, but the treating psychiatrist was not blinded and could prescribe any medication deemed clinically indicated for the patient. Improvement, side effects, and satisfaction were assessed throughout the study and at a 6-month follow-up visit. There was no significant difference in terms of symptom improvement, side effect burden, or satisfaction at 8 weeks or 6 months between patients in the GENE and treatment-as-usual arms, respectively. However, significantly more patients in the treatment-as-usual arm received selective serotonin reuptake inhibitors (SSRIs) compared with patients in the GENE arm (81.5% vs 66.7%). Therefore, there was no significant clinical impact when clinicians used combinatorial pharmacogenomic testing to guide treatment for depressed adolescents. If anything, this guidance influenced providers to more frequently prescribe medications that are not considered first-line for the treatment of depression in youths (serotonin-norepinephrine reuptake inhibitors [SNRIs], atypical antidepressants) and for which double-blind placebo-controlled trials have failed to demonstrate efficacy in depressed youths..
药物遗传学在指导儿童和青少年精神药理学治疗中的作用对许多临床医生来说仍然难以捉摸。由于缺乏坚实而全面的证据基础、足够的培训、教育和共识指南，商业推广药物遗传学检测面板有可能成为提供者的主要信息来源。这些测试通常包括多基因面板，并将药物分为彩色编码的bins。这些面板包括药代动力学 (PK) 和药效动力学 (PD) 基因，并使用组合算法，直接指导临床医生“按指示”使用药物或警告“中度基因-药物相互作用”或“显著基因-药物相互作用”可能存在。许多由行业赞助的成年人研究得出的结论是，当临床医生根据药物基因组学指导选择药物时，患者的治疗效果更好，尽管有些人对此方法持谨慎态度。为了在儿童和青少年精神病学的临床实践中提供关于药物遗传学检测面板的临床影响和潜力的证据，在本期杂志中，Vande Voort 及其同事报告了一项前瞻性试验的结果，该试验比较了基于组合药物遗传学检测指导的治疗与抑郁症青少年的常规治疗。作者将年龄在 13 至 18 岁、患有中度至重度重度抑郁症的青少年 (N = 176) 随机分为接受基于组合药物遗传学检测指导的治疗 (GENE 臂，n = 84) 或接受常规治疗 (治疗臂，n = 92)。患者和评估者被设盲，但治疗精神科医生未设盲，可根据患者的临床需要开任何药物。在整个研究过程中以及在 6 个月的随访中评估了改善情况、副作用和满意度。在第 8 周和 6 个月时，GENE 臂和治疗臂的患者在症状改善、副作用负担或满意度方面均无显著差异。然而，在治疗臂中，接受选择性 5-羟色胺再摄取抑制剂 (SSRIs) 的患者明显多于 GENE 臂中的患者 (81.5% vs. 66.7%)。因此，当临床医生使用组合药物基因组学检测来指导治疗抑郁症青少年时，并没有显著的临床影响。如果有的话，这种指导促使提供者更频繁地开处方治疗青少年抑郁症的非一线药物(去甲肾上腺素和 5-羟色胺再摄取抑制剂 [SNRIs]、非典型抗抑郁药)，而这些药物的双盲安慰剂对照试验未能证明在抑郁青少年中有效。
