Department of Internal Medicine and Sealy Center on Aging; Department of Preventive Medicine and Population Health; Institute for Translational Science; Office of Biostatistics, University of Texas Medical Branch, Galveston.
School of Medicine, University of Texas Southwestern Medical Center, Dallas.
Am J Med. 2022 Jul;135(7):e194-e206. doi: 10.1016/j.amjmed.2022.02.039. Epub 2022 Mar 25.
Gabapentinoids (GABAs) and serotonergic drugs (selective serotonin reuptake inhibitors [SSRIs]/serotonin and norepinephrine reuptake inhibitors [SNRIs]) are increasingly being prescribed as potential substitutes to opioids and benzodiazepines (benzos), respectively, to treat co-occurring pain and anxiety disorders. The toxicities of these drug classes and their combinations are not well understood.
We conducted a matched case-control study using 2013-2016 Medicare files linked to the National Death Index. Cases were enrollees who died from drug overdose. Controls were enrollees who died from other causes. Cases and controls were matched on patient characteristics and prior chronic conditions. Possession of any opioids, GABAs, benzos, and SSRIs/SNRIs in the month prior to death was defined as drug use. Combination drug use was defined as possessing at least 2 types of these prescriptions for an overlapping period of at least 7 days in the month prior to death.
Among 4323 matches, benzo possession was associated with twice the risk for drug overdose death in cases vs controls. Compared with opioid-benzo co-prescribing, combinations involving SSRIs/SNRIs and opioids (or GABAs) were associated with decreased risk (adjusted odds ratio 0.55; 95% confidence interval, 0.44-0.69 for opioids and SSRIs/SNRIs; adjusted odds ratio 0.59; 95% confidence interval, 0.44-0.79 for GABAs and SSRIs/SNRIs). Fatal drug overdose risk was similar in users of GABA-opioid, GABA-benzo, and opioid-benzo combinations.
Benzodiazepines, prescribed alone or in combination, were associated with an increased risk of drug overdose death. SSRIs/SNRIs were associated with lower risk of overdose death vs benzodiazepines. GABAs were not associated with decreased risk compared with opioids, raising concerns for GABAs' perceived relative safety.
加巴喷丁类药物（GABAs）和血清素能药物（选择性血清素再摄取抑制剂[SSRIs]/血清素和去甲肾上腺素再摄取抑制剂[SNRIs]）分别越来越多地被开为阿片类药物和苯二氮䓬类药物（苯并）的潜在替代品，以治疗同时发生的疼痛和焦虑障碍。这些药物类别的毒性及其组合的毒性尚未得到很好的理解。
我们使用 2013-2016 年医疗保险文件与国家死亡索引进行了匹配病例对照研究。病例是因药物过量而死亡的参保人。对照组是因其他原因死亡的参保人。病例和对照组根据患者特征和既往慢性疾病进行匹配。在死亡前一个月内拥有任何阿片类药物、GABAs、苯并和 SSRIs/SNRIs 被定义为药物使用。联合用药定义为在死亡前一个月的重叠期内至少同时使用 2 种这些处方。
在 4323 对匹配中，与对照组相比，苯并类药物的使用与药物过量死亡风险增加两倍相关。与阿片类药物-苯并类药物联合用药相比，涉及 SSRIs/SNRIs 和阿片类药物（或 GABAs）的组合与降低的风险相关（调整后的优势比为 0.55；95%置信区间，0.44-0.69 用于阿片类药物和 SSRIs/SNRIs；调整后的优势比为 0.59；95%置信区间，0.44-0.79 用于 GABAs 和 SSRIs/SNRIs）。GABA-阿片类、GABA-苯并类和阿片类药物-苯并类联合用药的使用者的致命药物过量风险相似。
单独或联合使用苯二氮䓬类药物与药物过量死亡风险增加相关。SSRIs/SNRIs 与苯并类药物相比，与较低的药物过量死亡风险相关。与阿片类药物相比，GABAs 与降低的风险无关，这引发了对 GABAs 相对安全性的担忧。
