INUBE Biosanitary University Research Institute, University of Extremadura, Badajoz, Spain.
University of Extremadura Medical School, Badajoz, Spain.
Transl Psychiatry. 2022 Oct 18;12(1):451. doi: 10.1038/s41398-022-02140-4.
This study of a cohort of 1-year treatment-compliant survivors of a suicide attempt examined for the first time whether a high CYP2D6-CYP2C19 metabolic capacity (pharmacogenes related to psychopathology, suicide, and attempt severity) and/or polypharmacy treatments predicted repeat suicide attempts, adjusting for sociodemographic and clinical factors as confounders. Of the 461 (63% women) consecutively hospitalized patients who attempted suicide and were evaluated and treated after an index attempt, 191 (67.5% women) attended their 6- and 12-month follow-up sessions. Clinicians were blinded to the activity scores (AS) of their genotypes, which were calculated as the sum of the values assigned to each allele (CYP2C19 *2, *17; CYP2D6 *3, *4, *4xN, *5, *6, *10, wtxN). No differences were found in polypharmacy prescription patterns and the variability of CYP2D6 and CYP2C19 genotypes between adherents and dropouts, but the formers were older, with a higher frequency of anxiety and bipolar disorders and fewer alcohol and substance use disorders. The risk of reattempts was higher for CYP2D6 ultrarapid (AS > 2) metabolizers (β = 0.561, p = 0.005) and violent suicide survivors (β = -0.219, p = 0.042) if the attempt occurred during the first 6-month period, individuals with an increased number of MINI DSM-IV Axis I mental disorders (β = 0.092, p = 0.032) during the second 6-month period and individuals with a combined high CYP2D6-CYP2C19 metabolic capacity (AS > 4) (β = 0.345, p = 0.024) and an increased use of drugs other than antidepressants, anxiolytics-depressants and antipsychotics-lithium (β = 0.088, p = 0.005) in multiple repeaters during both periods. CYP2D6 and CYP2C19 rapid metabolism and polypharmacy treatment for somatic comorbidities must be considered to prevent the severe side effects of short-term multiple suicide reattempts after a previous attempt.
这项研究对 1 年治疗依从性的自杀幸存者队列进行了研究，首次考察了高 CYP2D6-CYP2C19 代谢能力（与精神病理学、自杀和尝试严重程度相关的药物基因）和/或多药治疗是否可以预测重复自杀尝试，调整了混杂因素（社会人口统计学和临床因素）。在连续住院的 461 名（63%为女性）自杀未遂患者中，有 191 名（67.5%为女性）参加了 6 个月和 12 个月的随访。临床医生对他们的基因型活动评分（AS）不知情，该评分是每个等位基因赋值的总和（CYP2C19*2、17；CYP2D63、*4、*4xN、*5、*6、*10、wtxN）。依从组和脱落组之间的多药处方模式和 CYP2D6 和 CYP2C19 基因型的变异性没有差异，但前者年龄较大，焦虑和双相障碍的频率更高，酒精和物质使用障碍的频率更低。如果尝试发生在前 6 个月内，CYP2D6 超快代谢（AS>2）代谢物（β=0.561，p=0.005）和暴力自杀幸存者（β=-0.219，p=0.042）的再尝试风险更高，在第二个 6 个月期间患有更多的 MINI DSM-IV 轴 I 精神障碍（β=0.092，p=0.032），并且具有高 CYP2D6-CYP2C19 代谢能力（AS>4）（β=0.345，p=0.024）和增加使用抗抑郁药、抗焦虑药-抗抑郁药和抗精神病药-锂以外的药物（β=0.088，p=0.005）在两个时期的多个重复者中。对于躯体合并症，必须考虑 CYP2D6 和 CYP2C19 的快速代谢和多药治疗，以防止在先前尝试后短期多次自杀重试的严重副作用。
