Leach Michael J, Pratt Nicole L, Roughead Elizabeth E
Quality Use of Medicines and Pharmacy Research Centre, Sansom Institute, School of Pharmacy and Medical Sciences, University of South Australia, GPO Box 2471, Adelaide, SA, 5001, Australia.
Loddon Mallee Integrated Cancer Service, Bendigo Health Care Group, Bendigo, VIC, Australia.
Drugs Real World Outcomes. 2017 Jun;4(2):87-96. doi: 10.1007/s40801-017-0107-8.
Few studies have assessed the risk of hip fracture following concurrent use of psychoactive medicines, and none has investigated combinations with selective serotonin reuptake inhibitors.
To assess the risk of hip fracture in older people as a result of concurrent use of selective serotonin reuptake inhibitors and other psychoactive medicines.
A matched case-control design was employed. Cases were Australian Government Department of Veterans' Affairs beneficiaries aged over 65 years who experienced a hip fracture between 2009 and 2012. Each case was matched with up to four randomly selected controls of the same age (±2 years) and sex. Medicine-hip fracture associations were estimated via conditional logistic regression. The relative excess risk due to interaction (RERI) was calculated to determine whether combined effects differed from the sum of individual effects.
There were 8828 cases and 35,310 controls. The median age of subjects was 88 years and 63% were women. The risk of hip fracture was elevated for all medicines assessed individually, most notably selective serotonin reuptake inhibitors (initiation: odds ratio [OR] = 2.7, 95% confidence interval [CI] 2.1, 3.6) and opioids (initiation: OR = 2.3, 95% CI 1.9, 2.9). Combinations associated with an increased odds of hip fracture included addition of benzodiazepines to selective serotonin reuptake inhibitor therapy (OR = 3.0, 95% CI 1.9, 4.8; RERI = 0.9, 95% CI -0.5, 2.3), concurrent use of both opioids and selective serotonin reuptake inhibitors (OR = 2.2, 95% CI 1.9, 2.6; RERI = 0.1, 95% CI -0.3, 0.5), addition of opioids to selective serotonin reuptake inhibitor therapy (OR = 3.2, 95% CI 1.8, 5.5; RERI = -0.1, 95% CI -2.0, 1.7), and initiation of both benzodiazepines and selective serotonin reuptake inhibitors (OR = 4.7, 95% CI 1.7, 13; RERI = 1.3, 95% CI -3.8, 6.3). The RERI results suggested that the effect of each of these medicine combinations equalled the sum of the effects of individual medicine use.
In older people, the concurrent use of selective serotonin reuptake inhibitors and other psychoactive medicines increased the risk of hip fracture as much as the sum of the risks owing to individual medicine use. Our results highlight the need for prescribers to consider the sedative burden of medicines in each older patient as well as the potential for an additive risk of hip fracture when initiating additional psychoactive therapy.
很少有研究评估同时使用精神活性药物后髋部骨折的风险，且尚无研究调查与选择性5-羟色胺再摄取抑制剂的联合使用情况。
评估老年人同时使用选择性5-羟色胺再摄取抑制剂和其他精神活性药物导致髋部骨折的风险。
采用匹配病例对照设计。病例为2009年至2012年间发生髋部骨折的65岁以上澳大利亚退伍军人事务部受益人。每个病例与最多4名年龄（±2岁）和性别相同的随机选择的对照匹配。通过条件逻辑回归估计药物与髋部骨折的关联。计算交互作用所致相对超额危险度（RERI）以确定联合效应是否不同于个体效应之和。
共有8828例病例和35310名对照。受试者的中位年龄为88岁，63%为女性。单独评估的所有药物均使髋部骨折风险升高，最显著的是选择性5-羟色胺再摄取抑制剂（开始使用：比值比[OR]=2.7，95%置信区间[CI]2.1，3.6）和阿片类药物（开始使用：OR=2.3，95%CI1.9，2.9）。与髋部骨折几率增加相关的联合用药包括在选择性5-羟色胺再摄取抑制剂治疗中加用苯二氮䓬类药物（OR=3.0，95%CI1.9，4.8；RERI=0.9，95%CI -0.5，2.3）、同时使用阿片类药物和选择性5-羟色胺再摄取抑制剂（OR=2.2，95%CI1.9，2.6；RERI=0.1，95%CI -0.3，0.5）、在选择性5-羟色胺再摄取抑制剂治疗中加用阿片类药物（OR=3.2，95%CI1.8，5.5；RERI=-0.1，95%CI -2.0，1.7）以及开始使用苯二氮䓬类药物和选择性5-羟色胺再摄取抑制剂（OR=4.7，95%CI1.7，13；RERI=1.3，95%CI -3.8，6.3）。RERI结果表明，这些药物联合使用中的每一种的效应等于单独使用药物效应之和。
在老年人中，同时使用选择性5-羟色胺再摄取抑制剂和其他精神活性药物使髋部骨折风险增加的程度与单独使用药物的风险之和相同。我们的结果强调，开处方者在开始额外的精神活性药物治疗时，需要考虑每位老年患者药物的镇静负担以及髋部骨折的叠加风险可能性。
