Parkhomenko, postgraduate student of addiction psychiatry department.
Zastrozhin, MD, PhD, associate professor of addiction psychiatry department, head of laboratory of genetics and fundamental studies, Russian Medical Academy of Continuous Professional Education of the Ministry of Health of the Russian Federation, Moscow, Russian Federation; Moscow Research and Practical Centre on Addictions of the Moscow Department of Healthcare, Moscow, Russia; University of California, San Francisco, San Francisco, CA, USA.
Psychopharmacol Bull. 2022 Oct 27;52(4):52-60.
CYP2D6 subfamily isoenzymes play an important role in the biotransformation of haloperidol, and their activity may influence the efficacy and safety of haloperidol. The use of haloperidol is often associated with the occurrence of adverse drug reactions (ADRs), such as dyskinesia, acute dystonia, and orthostatic hypotension. Previous studies have demonstrated the relationship between the genetic polymorphism and CYP2D6 activity, as well as haloperidol efficacy and safety rates.
To evaluate the association of genetic polymorphism with the steady-state concentration of haloperidol in patients with acute alcohol-induced psychotic disorders (AIPDs).
The study involved 100 male patients with AIPD (average age 41.4 ± 14.4 years) who received haloperidol by injections in a dose of 5-10 mg/day. The efficacy profile was assessed using a validated psychometric PANSS scale (Positive and Negative Syndrome Scale). Therapy safety was assessed using the internationally validated UKU (Side-Effect Rating Scale) and SAS (Simpson-Angus Scale for Extrapyramidal Symptoms) scales. Genotyping was performed with the real-time polymerase chain reaction.
We revealed the statistically significant results in terms of therapy safety evaluation (dynamics of the UKU scores: () 8.00 [7.00; 10.00], () 15.0 [9.25; 18.0], p < 0.001; dynamics of the SAS scores: () 11.0 [9.0; 14.0], () 14.50 [12.0; 18.0], p < 0.001. Pharmacokinetic study showed a statistically significant difference across the groups with different genotypes: () 3.13 [2.32; 3.95], () 3.89 [2.92; 5.26], p = 0.010.
It can be concluded that patients with the genotype have a higher risk of ADRs compared to patients who carry the genotype. It was shown that genetic polymorphism has a statistically significant effect on the steady-state concentration of haloperidol.
CYP2D6 亚家族同工酶在氟哌啶醇的生物转化中发挥重要作用，其活性可能影响氟哌啶醇的疗效和安全性。氟哌啶醇的使用常与不良反应（ADR）的发生有关，如运动障碍、急性肌张力障碍和直立性低血压。先前的研究已经证明了基因多态性与 CYP2D6 活性以及氟哌啶醇疗效和安全性之间的关系。
评估基因多态性与急性酒精性精神病患者（AIPD）中氟哌啶醇稳态浓度的关系。
本研究纳入了 100 名男性 AIPD 患者（平均年龄 41.4±14.4 岁），他们每天接受 5-10mg 的氟哌啶醇注射治疗。使用经过验证的心理计量 PANSS 量表（阳性和阴性综合征量表）评估疗效。使用国际上经过验证的 UKU（副作用评定量表）和 SAS（锥体外系症状 Simpson-Angus 量表）量表评估治疗安全性。使用实时聚合酶链反应进行基因分型。
我们在治疗安全性评估方面发现了具有统计学意义的结果（UKU 评分的动态变化：（）8.00 [7.00；10.00]，（）15.0 [9.25；18.0]，p<0.001；SAS 评分的动态变化：（）11.0 [9.0；14.0]，（）14.50 [12.0；18.0]，p<0.001）。药代动力学研究显示，不同基因型组之间存在统计学显著差异：（）3.13 [2.32；3.95]，（）3.89 [2.92；5.26]，p=0.010。
可以得出结论，与携带 基因型的患者相比，携带 基因型的患者发生 ADR 的风险更高。研究表明，基因多态性对氟哌啶醇的稳态浓度具有统计学显著影响。
