双相情感障碍“旋转门”患者的CYP2D6基因分型：病例系列

CYP2D6 genotypes in revolving door patients with bipolar disorders: A case series.

作者信息

Seripa Davide, Lozupone Madia, Miscio Giuseppe, Stella Eleonora, La Montagna Maddalena, Gravina Carolina, Urbano Maria, di Mauro Lazzaro, Daniele Antonio, Greco Antonio, Logroscino Giancarlo, Panza Francesco, Bellomo Antonello

机构信息

Geriatric Unit and Gerontology-Geriatrics Research Laboratory, Department of Medical Sciences, IRCCS "Casa Sollievo della Sofferenza", San Giovanni Rotondo, Foggia Neurodegenerative Disease Unit, Department of Basic Medicine, Neuroscience, and Sense Organs, University of Bari "Aldo Moro", Bari Laboratory of Clinical Chemistry, Department of Clinical Pathology, IRCCS "Casa Sollievo della Sofferenza", San Giovanni Rotondo Psychiatric Unit, Department of Clinical and Experimental Medicine, University of Foggia, Foggia Institute of Neurology, Catholic University of Sacred Heart, Rome Department of Clinical Research in Neurology, Neurodegenerative Disease Unit, University of Bari "Aldo Moro", Azienda Ospedaliera "Card. G. Panico", Tricase, Lecce, Italy.

出版信息

Medicine (Baltimore). 2018 Sep;97(37):e11998. doi: 10.1097/MD.0000000000011998.

DOI:10.1097/MD.0000000000011998

PMID:30212929

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC6155952/

Abstract

RATIONALE

In psychiatric disorders, interindividual differences in cytochrome P450 (CYP)2D6 (CYP2D6) enzymatic activity could be responsible of adverse drug reactions (ADRs) and therapeutic failures (TFs) for CYP2D6-metabolized drugs, contributing to the periodical hospital readmissions of the revolving door (RD) condition.

PATIENT CONCERNS

We investigated CYP2D6 genotypes in a controlled series of 5 consecutive RD patients with Bipolar Disorder (BD).

DIAGNOSES

Psychiatric patients affected by Bipolar Disorder.

INTERVENTIONS

We defined TFs as a difference at the Brief Psychiatric Rating Scale score ΔBPRS < 25% at each 1-week of stable treatment, and ADRs as the onset of extrapyramidal symptoms and/or metabolic impairment with weight gain.

OUTCOMES

At 3 months, a mean number of 2.75 ± 1.26 ADR and a mean ΔBPRS score of 16.07 ± 0.05% were observed. At 6 months of follow-up, compared to the only patient without BD (ΔBPRS < 32.10%), BD patients (n = 4) showed TFs (ΔBPRS < 25%). CYP2D6 genotyping revealed intermediate metabolizer phenotypes for BD patients and an extensive metabolizer phenotype for the patient without BD. In BD patients, the ratio of drugs maintained/discontinued for TFs or ADRs was 1.75 for non-CYP2D6 versus 0.33 for CYP2D6 interacting drugs, while the proportion of ADR:TF was 0:4 versus 6:3.

LESSONS

Our findings may suggest that CYP2D6 clinically relevant genotypes may be involved in the unwanted outcomes observed in RD patients with BD.

摘要

原理

在精神疾病中，细胞色素P450（CYP）2D6酶活性的个体差异可能导致CYP2D6代谢药物出现药物不良反应（ADR）和治疗失败（TF），进而导致“旋转门”（RD）状态下的周期性住院再入院。

患者关注

我们对连续5例患有双相情感障碍（BD）的RD患者进行了对照研究，调查了CYP2D6基因型。

诊断

患有双相情感障碍的精神科患者。

干预措施

我们将TF定义为在稳定治疗的每1周，简明精神病评定量表得分变化ΔBPRS＜25%，将ADR定义为锥体外系症状和/或体重增加导致的代谢损害的出现。

结果

在3个月时，观察到平均ADR数为2.75±1.26，平均ΔBPRS评分为16.07±0.05%。在随访6个月时，与唯一没有BD的患者（ΔBPRS＜32.10%）相比，BD患者（n = 4）出现了TF（ΔBPRS＜25%）。CYP2D6基因分型显示BD患者为中间代谢型，而没有BD的患者为广泛代谢型。在BD患者中，因TF或ADR而维持/停用的非CYP2D6药物的比例为1.75，而CYP2D6相互作用药物的比例为0.33，ADR与TF的比例为0:4与6:3。