Tanenbaum Centre for Pharmacogenetics, Neurogenetics Section, Molecular Brain Sciences Research Department, Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health, Toronto, ON, Canada.
Department of Psychiatry, University of Toronto, Toronto, ON, Canada.
Transl Psychiatry. 2022 Mar 14;12(1):101. doi: 10.1038/s41398-022-01847-8.
The pharmacological treatment of depression consists of stages of trial and error, with less than 40% of patients achieving remission during first medication trial. However, in a large, randomized-controlled trial (RCT) in the U.S. ("GUIDED"), significant improvements in response and remission rates were observed in patients who received treatment guided by combinatorial pharmacogenomic testing, compared to treatment-as-usual (TAU). Here we present results from the Canadian "GAPP-MDD" RCT. This 52-week, 3-arm, multi-center, participant- and rater-blinded RCT evaluated clinical outcomes among patients with depression whose treatment was guided by combinatorial pharmacogenomic testing compared to TAU. The primary outcome was symptom improvement (change in 17-item Hamilton Depression Rating Scale, HAM-D17) at week 8. Secondary outcomes included response (≥50% decrease in HAM-D17) and remission (HAM-D17 ≤ 7) at week 8. Numerically, patients in the guided-care arm had greater symptom improvement (27.6% versus 22.7%), response (30.3% versus 22.7%), and remission rates (15.7% versus 8.3%) compared to TAU, although these differences were not statistically significant. Given that the GAPP-MDD trial was ultimately underpowered to detect statistically significant differences in patient outcomes, it was assessed in parallel with the larger GUIDED RCT. We observed that relative improvements in response and remission rates were consistent between the GAPP-MDD (33.0% response, 89.0% remission) and GUIDED (31.0% response, 51.0% remission) trials. Together with GUIDED, the results from the GAPP-MDD trial indicate that combinatorial pharmacogenomic testing can be an effective tool to help guide depression treatment in the context of the Canadian healthcare setting (ClinicalTrials.gov NCT02466477).
抑郁症的药物治疗包括试错阶段，不到 40%的患者在首次药物试验中达到缓解。然而，在美国的一项大型随机对照试验（GUIDED）中，与常规治疗（TAU）相比，接受组合药物基因组学检测指导治疗的患者在反应和缓解率方面有显著改善。在这里，我们介绍加拿大“GAPP-MDD” RCT 的结果。这项为期 52 周、3 臂、多中心、参与者和评估者盲法 RCT 评估了接受组合药物基因组学检测指导治疗与 TAU 治疗的抑郁症患者的临床结局。主要结局是第 8 周时症状改善（17 项汉密尔顿抑郁量表，HAM-D17 的变化）。次要结局包括第 8 周时的反应（HAM-D17 下降≥50%）和缓解（HAM-D17≤7）。数值上，与 TAU 相比，指导护理组的患者症状改善（27.6%比 22.7%）、反应（30.3%比 22.7%）和缓解率（15.7%比 8.3%）更高，尽管这些差异没有统计学意义。由于 GAPP-MDD 试验最终在检测患者结局的统计学差异方面能力不足，因此与更大的 GUIDED RCT 并行评估。我们观察到，GAPP-MDD（反应率 33.0%，缓解率 89.0%）和 GUIDED（反应率 31.0%，缓解率 51.0%）试验之间的反应和缓解率相对改善是一致的。与 GUIDED 一起，GAPP-MDD 试验的结果表明，组合药物基因组学检测可以成为帮助指导加拿大医疗保健环境中抑郁症治疗的有效工具（ClinicalTrials.gov NCT02466477）。
