Zastrozhin Michael S, Sorokin Aleksandr S, Agibalova Tatyana V, Grishina Elena A, Antonenko Anastasiya Р, Rozochkin Ilya N, Duzhev Denis V, Skryabin Valentine Y, Galaktionova Tatyana E, Barna Ilya V, Orlova Anna V, Aguzarov Albert D, Savchenko Ludmila M, Bryun Evgeny A, Sychev Dmitry A
Russian Medical Academy of Continuous Professional Education, Ministry of Health of the Russian Federation, Moscow, Russia.
Moscow Research and Practical Centre on Addictions, Moscow Department of Healthcare, Moscow, Russia.
Hum Psychopharmacol. 2018 Nov;33(6):e2677. doi: 10.1002/hup.2677. Epub 2018 Oct 25.
Although pharmacogenetic tests provide the information on a genotype and the predicted phenotype, these tests themselves do not provide the interpretation of data for a physician. There are currently approximately two dozen pharmacogenomic clinical decision support systems used in psychiatry. Implementation of clinical decision support systems capable of forming recommendations on drug and dose selection according to the results of pharmacogenetic testing is an urgent task. Fulfillment of this task may allow increasing the efficacy of therapy and decreasing the risk of undesirable side effects.
The study included 51 male patients (21 in the main group and 30 in the control group) with alcohol withdrawal syndrome. To evaluate the efficacy and safety of therapy, several international psychometric scales and rating scales to measure side effects were used. Genotyping was performed using real-time polymerase chain reaction with allele-specific hybridization. Pharmacogenetic test results were interpreted using free software PGX2 (www.pgx2.com).
Statistically significant differences between the scores derived from all psychometric scales were revealed. For instance, the total score on CIWA-Ar scale by day 3 was 13.5 [11.2; 16.0] for the main group and 18.0 [17.0; 22.0] (p < 0.001) for the control group; by day 5, it was 6.5 [4.2; 8.0] for the main group and 15.0 [14.0; 16.0] (p < 0.001) for the control group. The UKU side effect rating scale (UKU) also revealed a statistically significant difference. The total score on UKU scale by day 3 was 6.0 [5.0; 7.0] for the main group and 7.0 [6.0; 8.0] (p < 0.001) for the control group; by day 5, this difference grew significantly: 5.5 [3.0; 9.0] for the main group and 14.0 [12.0; 19.0] (p < 0.001) for the control group. The groups were representative (there was no difference between the scores at the inclusion of patients).
Pharmacogenetic-guided personalization of drug dose in patients with alcohol withdrawal syndrome can reduce the risk of undesirable side effects and pharmacoresistance. It allows recommending the use of pharmacogenomic clinical decision support systems for optimizing drug dosage.
尽管药物遗传学检测可提供基因型和预测表型的信息，但这些检测本身并不能为医生提供数据解读。目前在精神病学中大约有二十多种药物基因组临床决策支持系统。实施能够根据药物遗传学检测结果就药物和剂量选择形成建议的临床决策支持系统是一项紧迫任务。完成这项任务可能会提高治疗效果并降低不良副作用的风险。
该研究纳入了51名患有酒精戒断综合征的男性患者（主要组21名，对照组30名）。为评估治疗的疗效和安全性，使用了几种国际心理测量量表和用于测量副作用的评定量表。采用等位基因特异性杂交的实时聚合酶链反应进行基因分型。使用免费软件PGX2（www.pgx2.com）解读药物遗传学检测结果。
所有心理测量量表得出的分数之间存在统计学上的显著差异。例如，主要组在第3天CIWA - Ar量表的总分是13.5[11.2；16.0]，对照组是18.0[17.0；22.0]（p < 0.001）；在第5天，主要组是6.5[4.2；8.0]，对照组是15.0[14.0；16.0]（p < 0.001）。UKU副作用评定量表（UKU）也显示出统计学上的显著差异。主要组在第3天UKU量表的总分是6.0[5.0；7.0]，对照组是7.0[6.0；8.0]（p < 0.001）；在第5天，这种差异显著增大：主要组是5.5[3.0；9.0]，对照组是14.0[12.0；19.0]（p < 0.001）。各组具有代表性（患者纳入时分数无差异）。
酒精戒断综合征患者药物剂量的药物遗传学指导个性化可降低不良副作用和药物耐药性的风险。这使得推荐使用药物基因组临床决策支持系统来优化药物剂量成为可能。
