Graduate Institute of Clinical Pharmacy, College of Medicine, National Taiwan University, Taipei, Taiwan.
Taiwan Drug Relief Foundation, Taipei, Taiwan.
Pharmacoepidemiol Drug Saf. 2024 Jun;33(6):e5847. doi: 10.1002/pds.5847.
The use of benzodiazepines and Z-hypnotics during pregnancy has raised significant concerns in recent years. However, there are limited data that capture the prescription patterns and predisposing factors in use of these drugs, particularly among women who have been long-term users of benzodiazepines and Z-hypnotics before pregnancy.
This population-based cohort study comprised 2 930 988 pregnancies between 2004 and 2018 in Taiwan. Women who were dispensed benzodiazepines or Z-hypnotics during pregnancy were identified and further stratified into groups based on their status before pregnancy: long-term users (with a supply of more than 180 days within a year), short-term users (with a supply of less than 180 days within a year), and nonusers. Trends in the use of benzodiazepines or Z-hypnotics and concomitant use with antidepressants or opioids were assessed. Logistic regression models were utilized to identify factors associated with use of these drugs during pregnancy, and interrupted time series analyses (ITSA) were employed to evaluate utilization patterns of these drugs across different pregnancy-related periods.
The overall prevalence of benzodiazepine and Z-hypnotic use was 3.5% during pregnancy. Among prepregnancy long-term users, an upward trend was observed. The concomitant use of antidepressants or opioids among exposed women increased threefold (from 8.6% to 23.1%) and sixfold (from 0.3% to 1.7%) from 2004 to 2018, respectively. Women with unhealthy lifestyle behaviors, such as alcohol abuse (OR 2.48; 95% CI, 2.02-3.03), drug abuse (OR 10.34; 95% CI, 8.46-12.64), and tobacco use (OR 2.19; 95% CI, 1.96-2.45), as well as those with psychiatric disorders like anxiety (OR 6.99; 95% CI, 6.77-7.22), insomnia (OR 15.99; 95% CI, 15.55-16.45), depression (OR 9.43; 95% CI, 9.07-9.80), and schizophrenia (OR 21.08; 95% CI, 18.76-23.69), and higher healthcare utilization, were more likely to use benzodiazepines or Z-hypnotics during pregnancy. ITSA revealed a sudden decrease in use of benzodiazepines and Z-hypnotics after recognition of pregnancy (level change -0.55 percentage point; 95% CI, -0.59 to -0.51). In contrast, exposures to benzodiazepines and Z-hypnotics increased significantly after delivery (level change 0.12 percentage point; 95% CI, 0.09 to 0.16).
In this cohort study, an increased trend of benzodiazepine and Z-hypnotic use during pregnancy among prepregnancy long-term users, as well as concomitant use with antidepressants or opioids were found. The findings have highlighted the existence of various risk factors associated with the use of these drugs during pregnancy. Utilization patterns varied across different stages of pregnancy, highlighting the need for prescription guidelines and educational services for women using these drugs during pregnancy.
近年来，孕妇使用苯二氮䓬类药物和 Z 类催眠药引起了广泛关注。然而，关于这些药物的处方模式和易患因素的数据有限，特别是在长期使用苯二氮䓬类药物和 Z 类催眠药的孕妇中。
本基于人群的队列研究纳入了 2004 年至 2018 年期间台湾的 2930988 例妊娠。确定了在怀孕期间使用苯二氮䓬类药物或 Z 类催眠药的女性，并根据其妊娠前的状况进一步分为以下几组：长期使用者（一年内供应超过 180 天）、短期使用者（一年内供应少于 180 天）和非使用者。评估了苯二氮䓬类药物或 Z 类催眠药的使用趋势以及与抗抑郁药或阿片类药物的同时使用情况。利用逻辑回归模型确定了与怀孕期间使用这些药物相关的因素，并利用中断时间序列分析（ITSA）评估了这些药物在不同妊娠相关时期的使用模式。
在怀孕期间，苯二氮䓬类药物和 Z 类催眠药的总体使用率为 3.5%。在妊娠前的长期使用者中，观察到上升趋势。暴露妇女中抗抑郁药或阿片类药物的同时使用增加了三倍（从 2004 年的 8.6%增加到 2018 年的 23.1%）和六倍（从 2004 年的 0.3%增加到 2018 年的 1.7%）。有不健康生活方式行为的妇女，如滥用酒精（OR 2.48；95%CI，2.02-3.03）、药物滥用（OR 10.34；95%CI，8.46-12.64）和吸烟（OR 2.19；95%CI，1.96-2.45），以及患有焦虑症（OR 6.99；95%CI，6.77-7.22）、失眠症（OR 15.99；95%CI，15.55-16.45）、抑郁症（OR 9.43；95%CI，9.07-9.80）和精神分裂症（OR 21.08；95%CI，18.76-23.69）等精神疾病以及有较高医疗保健利用率的妇女，更有可能在怀孕期间使用苯二氮䓬类药物或 Z 类催眠药。ITSA 显示，妊娠后苯二氮䓬类药物和 Z 类催眠药的使用突然减少（水平变化-0.55 个百分点；95%CI，-0.59 至-0.51）。相比之下，产后暴露于苯二氮䓬类药物和 Z 类催眠药的情况显著增加（水平变化 0.12 个百分点；95%CI，0.09 至 0.16）。
在这项队列研究中，妊娠前长期使用苯二氮䓬类药物和 Z 类催眠药的孕妇中，以及与抗抑郁药或阿片类药物同时使用的孕妇中，苯二氮䓬类药物和 Z 类催眠药的使用呈上升趋势。研究结果突出了与孕妇使用这些药物相关的各种风险因素的存在。在不同的妊娠阶段，这些药物的使用模式存在差异，这表明需要为孕妇使用这些药物制定处方指南和教育服务。
