Psychiatry Research, Northwell Health, Behavioral Health Pavilion, Zucker Hillside Hospital, 7559 263rd Street, Glen Oaks, NY, 11004, USA.
Hofstra Northwell School of Medicine, Hempstead, NY, USA.
Eur J Clin Pharmacol. 2019 Aug;75(8):1109-1116. doi: 10.1007/s00228-019-02675-4. Epub 2019 Apr 9.
To assess in a large naturalistic sample, whether clinical response to a treatment with venlafaxine is associated with different patterns of plasma concentrations of active moiety, AM (sum of venlafaxine (VEN) and its active metabolite O-desmethylvenlafaxine (ODVEN)).
Applying a regression model, plasma concentrations and plasma concentrations corrected-by-dosage (C/D) for AM were included as independent variable with Clinical Global Impressions-Improvement (CGI-I) scale ratings as dependent variable. Moreover, AM, VEN, and ODVEN were compared between treatment responders and non-responders, defining response as much or very much improved on the CGI-I scale based on the non-parametric Mann-Whitney U (M-W-U) test with a significance level of 0.05.
No correlations were found between AM and C/D AM plasma concentrations and CGI-I ratings (regression coefficient 0.0, CI 0.000, 0.001, p = 0.492 for AM and 0.047, CI - 0.065, 0.159, p = 0.408 for C/D AM). Venlafaxine daily dosage did not differ between responders and non-responders (217.7 ± 76.9 vs. 222.0 ± 72.7 mg/day, p = 0.45 for M-W-U). Responders displayed lower ODVEN (p = 0.033) and AM (p = 0.031) plasma concentrations than non-responders (p = 0.033 and 0.031, respectively for M-W-U). No other differences were detected. Using a cut-off level of 400 ng/mL for AM concentrations, a higher percentage of responders was reported in the group of patients with AM < 400 ng/mL (13.04%) compared to patients with AM > 400 ng/mL (8%) (p = 0.038).
Higher ODVEN and AM concentrations in non-responders than in responders indicate that treatment escalation above upper thresholds of therapeutic reference ranges of venlafaxine is not promising. Hence, the therapeutic reference range for venlafaxine can help in improving outcomes in a measurement-based care model that takes advantage of therapeutic drug monitoring.
在一项大型自然主义样本中评估，治疗文拉法辛后临床反应是否与活性部分（文拉法辛（VEN）和其活性代谢物 O-去甲文拉法辛（ODVEN）的总和，AM）的不同血浆浓度模式相关。
应用回归模型，将 AM 的血浆浓度和经剂量校正的血浆浓度（C/D）作为自变量，临床总体印象-改善量表（CGI-I）评分作为因变量。此外，根据非参数曼-惠特尼 U（M-W-U）检验，以 CGI-I 量表上的改善程度为界值（显著水平为 0.05），将 AM、VEN 和 ODVEN 之间的差异定义为治疗反应者和非反应者之间的差异。
未发现 AM 和 C/D AM 血浆浓度与 CGI-I 评分之间存在相关性（回归系数 0.0，CI 0.000，0.001，p=0.492 对于 AM 和 0.047，CI-0.065，0.159，p=0.408 对于 C/D AM）。反应者和非反应者之间的文拉法辛日剂量无差异（217.7±76.9 与 222.0±72.7 mg/天，p=0.45，M-W-U）。与非反应者相比，反应者的 ODVEN（p=0.033）和 AM（p=0.031）血浆浓度更低（p=0.033 和 0.031，分别为 M-W-U）。未发现其他差异。使用 AM 浓度的 400ng/mL 作为截断值，与 AM>400ng/mL 的患者相比，AM<400ng/mL 组的反应者比例更高（13.04% 与 8%，p=0.038）。
非反应者的 ODVEN 和 AM 浓度高于反应者，表明升高文拉法辛治疗参考范围上限以上的治疗剂量并不可行。因此，文拉法辛的治疗参考范围有助于提高基于治疗药物监测的测量为基础的护理模型的结果。
