Department of Psychiatry and Psychology, Mayo Clinic, Rochester, MN 55905, USA.
Transl Psychiatry. 2011 May 10;1(5):e6. doi: 10.1038/tp.2011.7.
The authors tested the hypothesis that pharmacogenomic genotype knowledge is associated with better clinical and cost outcomes in depressed patients, after controlling for other factors that might differentiate tested and non-tested patients. Medical records of 251 patients, seen in the Mayo Clinic Rochester outpatient psychiatric practice, who had patient health questionnaire-9 (PHQ-9) scores before and after consultation, were reviewed. Comparisons of differences in pre-consultation and post-consultation depression scores and slopes between tested and non-tested patients and between genotype categories of tested patients, were evaluated, along with healthcare cost and utilization comparisons between tested and non-tested patients, using Kruskal-Wallis tests, Wilcoxon rank-sum tests and group mean comparisons, controlling for significant univariate demographic and clinical differences. Tested patients had significantly higher depression diagnosis frequency, baseline PHQ-9 scores, family history of depression, psychiatric hospitalization history, and higher numbers of antidepressant, mood stabilizer and antipsychotic medication trials. After controlling for these differences, there were no differences between tested and non-tested patients in post-baseline depression scores or slopes for CYP genotype categories. For patients with 5-HTTLPR testing, there was significantly more depression score improvement for patients with the long/long genotype at time 4 (N=55, χ(2)-value=8.0492, P=0.018) and at time 5 (N=44, χ(2)-value=6.1492, P=0.046). For a subgroup (n=46) with ≥two pre- and ≥two post-baseline PHQ-9 scores, the mean difference between pre-baseline and post-baseline PHQ-9 score slopes for tested patients was -0.08 (median -0.01; range -1.20 to 0.15) compared with 0.13 (median 0.02; range -0.18 to 2.16) for non-tested patients (P=0.03). Among genotype categories, mean differences between pre-consultation and post-consultation slopes were significantly better for poor CYP2D6 metabolizers than intermediate or extensive metabolizers (P=0.04); there was a trend for slope differences to be better for 5-HTTLPR long/long genotype patients (P=0.06). Subsets of local tested and consultant-adjusted non-tested controls (n=19), who had 8 years of longitudinal care within the health system, had similar overall mean healthcare costs before and after testing; however, tested patients on average had significantly fewer time-adjusted post-baseline psychiatric admissions (0.8 vs 3.8, P=0.04) and fewer time-adjusted psychiatric consultations and comprehensive mental health-specialty evaluations (4.2 vs 9.9, P=0.03). Prospective study is indicated as to whether and how pharmacogenomic testing in a psychiatric consultation practice may improve clinical and cost outcomes.
作者测试了这样一个假设,即在控制其他可能区分测试和未测试患者的因素后,药物基因组基因型知识与抑郁患者的临床和成本结果更好相关。对在梅奥诊所罗切斯特门诊精神病学实践中接受过患者健康问卷-9(PHQ-9)评分前后咨询的 251 名患者的医疗记录进行了回顾。评估了测试和未测试患者之间以及测试患者基因型类别的预咨询和后咨询抑郁评分和斜率之间的差异,以及测试和未测试患者之间的医疗保健成本和利用率比较,使用 Kruskal-Wallis 检验、Wilcoxon 秩和检验和组均数比较,控制了重要的单变量人口统计学和临床差异。测试患者的抑郁诊断频率、基线 PHQ-9 评分、抑郁家族史、精神病住院史更高,以及使用抗抑郁药、情绪稳定剂和抗精神病药的试验次数更多。在控制这些差异后,测试和未测试患者的基线后抑郁评分或 CYP 基因型类别的斜率没有差异。对于 5-HTTLPR 测试患者,在第 4 时间点(N=55,X(2)-值=8.0492,P=0.018)和第 5 时间点(N=44,X(2)-值=6.1492,P=0.046)时,长/长基因型患者的抑郁评分明显改善。对于具有≥两次基线前和≥两次基线后 PHQ-9 评分的亚组(n=46),测试患者的基线前和基线后 PHQ-9 评分斜率之间的平均差异为-0.08(中位数-0.01;范围-1.20 至 0.15),而非测试患者为 0.13(中位数 0.02;范围-0.18 至 2.16)(P=0.03)。在基因型类别中,与中间或广泛代谢物相比,较差的 CYP2D6 代谢物的预咨询和后咨询斜率之间的平均差异明显更好(P=0.04);5-HTTLPR 长/长基因型患者的斜率差异趋势更好(P=0.06)。在当地测试和顾问调整的非测试对照组(n=19)中,有 8 年的纵向医疗保健系统护理,在测试前后具有相似的总体平均医疗保健成本;然而,测试患者的平均平均基线后精神病入院次数明显减少(0.8 次对 3.8 次,P=0.04),以及平均基线后精神病咨询和综合心理健康专业评估次数减少(4.2 次对 9.9 次,P=0.03)。需要进行前瞻性研究,以确定在精神病咨询实践中进行药物基因组检测是否以及如何改善临床和成本结果。