The Effect of Genetic Polymorphisms on Patients Being Administered Benzodiazepines: A Systematic Review

Introduction Benzodiazepines are used in anesthesia and other clinical settings, including alcohol withdrawal syndrome and the intensive care unit, due to their sedative, anxiolytic, and relaxant effects. Genetic polymorphisms that differ between patients can influence drug metabolism, clearance, and receptor function, and therefore can produce varying responses. This systematic review aims to synthesize current literature regarding the impact of genetic polymorphisms on benzodiazepine administration for patients in different settings. Methods A literature search was conducted using four databases: PubMed, Cochrane Library, Virtual Health Library (VHL), and Web of Science (WOS). The search was conducted following PRISMA guidelines. All relevant articles were assessed for quality assessment using STROBE, CONSORT, and CARE guidelines. Independent reviewers evaluated studies based on eligibility criteria and analyzed relevant studies. Results Genetic polymorphisms were assessed based on gain-of-function and loss-of-function alleles. Gain-of-function mutations were found to increase enzymatic function, causing increased drug clearance and decreased plasma concentration. Gene variants were found to affect either pharmacokinetics, such as in CYP3A4, CYP3A5, CYP2C9, and CYP2C19, or affect the pharmacodynamics in GARB1, MDR1, ABCG2, and ABCC2. These polymorphisms indicated a need for increased dosage, decreased sedation duration and depth, and decreased recovery time. Loss-of-function mutations were found to decrease enzymatic function, leading to decreased drug clearance and increased plasma concentration. These mutations indicated a need for decreased dosage, increased sedation duration and depth, and increased recovery times. Conclusion Genetic polymorphisms can affect benzodiazepine sedation dosage, duration, depth, adverse events, and recovery time. These findings suggest that there may be a benefit to screening patients’ genetic profiles before administering benzodiazepines, yet there is a need for further research to determine clinical implications.