Scherf-Clavel Maike, Weber Heike, Weiß Carolin, Klüpfel Catherina, Stonawski Saskia, Hommers Leif, Unterecker Stefan, Domschke Katharina, Menke Andreas, Kittel-Schneider Sarah, Walther Sebastian, Deckert Jürgen, Erhardt-Lehmann Angelika
Department of Psychiatry, Psychosomatics, and Psychotherapy, Center of Mental Health, University Hospital of Würzburg, Würzburg, Germany.
Interdisciplinary Center for Clinical Research, University Hospital of Würzburg, Würzburg, Germany.
J Psychopharmacol. 2025 Aug;39(8):847-854. doi: 10.1177/02698811251337387. Epub 2025 May 12.
Psychopharmacotherapy with mirtazapine is commonplace. Lower serum concentrations of mirtazapine were reported in smokers due to induction. However, no previous study that investigated genetics and mirtazapine treatment considered inducing parameters.
We aimed to investigate the association of variants, mirtazapine serum concentration, and treatment outcome, considering the smoking status of the patients.
Two depression cohorts were investigated for the association between serum concentration and treatment response of mirtazapine and -163C>A (rs762551) and -3860G>A (rs2069514) genotype groups, also considering smoking status, sex, and age of the patients. In total, 124 patients (82 non-smokers and 42 smokers) were eligible for the analyses.
Dose-corrected serum concentration (CD) of mirtazapine was associated with smoking status, sex, and age, with lower CD in smokers, females, and older patients. Considering non-smokers and genotype-grouped smokers, CD of mirtazapine in normal metabolizer smokers ( = 6) did not differ from CD of non-smokers. By contrast, smokers carrying the *1A/*1F and *1F/*1F genotype groups showed 34.4% and 33.4% lower mirtazapine CD compared to non-smokers.
As yet, for clinical practice, it may be more relevant to focus on smoking status than on the gene variants. Considering the relevant impact of smoking on the mirtazapine CD, physicians should monitor an increase in side effects due to the expected increase in mirtazapine serum concentrations. In these cases, measurement of mirtazapine CD and/or subsequent dosage reduction is recommended. The clinical relevance of genotyping prior to treatment with drugs metabolized by needs further investigation.
使用米氮平进行心理药物治疗很常见。据报道，由于诱导作用，吸烟者体内米氮平的血清浓度较低。然而，之前没有研究在调查遗传学与米氮平治疗时考虑诱导参数。
我们旨在研究基因变体、米氮平血清浓度和治疗结果之间的关联，并考虑患者的吸烟状况。
对两个抑郁症队列进行研究，以探讨米氮平的血清浓度与治疗反应以及-163C>A（rs762551）和-3860G>A（rs2069514）基因型组之间的关联，同时考虑患者的吸烟状况、性别和年龄。共有124名患者（82名非吸烟者和42名吸烟者）符合分析条件。
米氮平的剂量校正血清浓度（CD）与吸烟状况、性别和年龄有关，吸烟者、女性和老年患者的CD较低。考虑非吸烟者和按基因型分组的吸烟者，正常代谢型吸烟者（n = 6）的米氮平CD与非吸烟者的CD没有差异。相比之下，携带*1A/1F和1F/*1F基因型组的吸烟者的米氮平CD比非吸烟者分别低34.4%和33.4%。
到目前为止，对于临床实践来说，关注吸烟状况可能比关注基因变体更重要。考虑到吸烟对米氮平CD的相关影响，医生应监测由于米氮平血清浓度预期升高而导致的副作用增加。在这些情况下，建议测量米氮平CD和/或随后减少剂量。在使用由[具体酶]代谢的药物治疗前进行基因分型的临床相关性需要进一步研究。
