A study of the safety and harms of antidepressant drugs for older people: a cohort study using a large primary care database
A study of the safety and harms of antidepressant drugs for older people: a cohort study using a large primary care database
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DOI：
10.3310/hta15280
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发表时间：
2011-08-01
影响因子：
3.6
通讯作者：
Hippisley-Cox, J.
中科院分区：
文献类型：
--
作者：
Coupland, C. A. C.;Dhiman, P.;Hippisley-Cox, J.
目的：本研究的目的是确定老年人抗抑郁药物治疗的相对安全性和风险平衡。该研究的目的是(1)确定老年抑郁症患者预定不良事件的相对和绝对风险，比较抗抑郁药物[三环及相关抗抑郁药（TCAs），选择性血清素再摄取抑制剂（SSRIs），单胺氧化酶抑制剂（MAOIs）和其他抗抑郁药物]和常用处方药物与非使用抗抑郁药物；(2)直接比较ssri类药物与TCAs不良事件的风险；(3)确定与抗抑郁药物剂量和持续时间的关系；(4)描述老年抑郁症患者使用抗抑郁药的模式；(5)估计抗抑郁药物和初级保健就诊的费用。设计：对65岁及以上诊断为抑郁症的患者进行队列研究。背景：该研究基于英国570个普通诊所，这些诊所为QResearch数据库提供数据。参与者：1996年1月1日至2007年12月31日期间，年龄在65岁至100岁之间被诊断为新发抑郁症的患者。参与者随访至2008年12月31日。干预措施：对感兴趣的暴露进行抗抑郁药物治疗。将抗抑郁药物分为主要类别，并确定常用的个体化药物。主要结局指标：13项预先确定的结局指标：全因死亡率、心源性猝死、自杀、自杀未遂/自残、心肌梗死、中风/短暂性脑缺血发作（TIA）、跌倒、骨折、上消化道出血、癫痫/癫痫发作、道路交通事故、药物不良反应和低钠血症。结果：总共60,746例患者被纳入研究队列。其中，54,038人（89.0%）在随访期间至少接受过一次抗抑郁药处方。抗抑郁药物与不良结果的关联在7种结果中有显著差异。SSRIs与跌倒（1.66,95%可信区间（Cl） 1.58至1.73）和低钠血症（1.52,95% Cl 1.33至1.75）的校正风险比最高相关，其他抗抑郁药物组与全因死亡率（1.66,95% Cl 1.56至1.77）、自杀未遂/自残（5.16,95% Cl 3.90至6.83）、中风/TIA （1.37, 95% Cl 1.22至1.55）、骨折（1.63,95% Cl 1.45至1.83）和癫痫/发作(2.24，95% CI 1.60 - 3.15)，与未使用抗抑郁药时相比。tca在任何结果中都没有最高的HR。不同药物对7种结果的相关性也有显著差异，其中曲唑酮、米氮平和文拉法辛与其中几种结果的相关性最高。在诊断后5年期间，（所有抗抑郁药处方）的平均增量成本在阿米替林51.58和文拉法辛641.18之间。结论：本研究发现抗抑郁药物的使用与老年人的一些不良事件之间存在关联。没有证据表明，与TCAs相比，SSRIs或其他抗抑郁药物组中的药物与任何不良后果的风险降低有关；然而，它们可能与某些结果的风险增加有关。在个别药物曲唑酮中，米氮平和文拉法辛与某些结果的最高发生率相关。适应症偏倚和残留的混杂因素可以解释一些研究结果。开具抗抑郁药处方的风险需要与这些药物的潜在益处进行权衡。
Objectives: The aim of this study was to establish the relative safety and balance of risks for antidepressant treatment in older people. The study objectives were to (1) determine relative and absolute risks of predefined adverse events in older people with depression, comparing classes of antidepressant drugs [tricyclic and related antidepressants (TCAs), selective serotonin reuptake inhibitors (SSRIs), monoamine oxidase inhibitors (MAOIs) and other antidepressants] and commonly prescribed individual drugs with non-use of antidepressant drugs; (2) directly compare the risk of adverse events for SSRIs with TCAs; (3) determine associations with dose and duration of antidepressant medication; (4) describe patterns of antidepressant use in older people with depression; and (5) estimate costs of antidepressant medication and primary care visits.Design: A cohort study of patients aged 65 years and over diagnosed with depression.Setting: The study was based in 570 general practices in the UK supplying data to the QResearch database.Participants: Patients diagnosed with a new episode of depression between the ages of 65 and 100 years, from 1 January 1996 to 31 December 2007. Participants were followed up until 31 December 2008.Interventions: The exposure of interest was treatment with antidepressant medication. Antidepressant drugs were grouped into the major classes and commonly prescribed individual drugs were identified.Main outcome measures: There were 13 predefined outcome measures: all-cause mortality, sudden cardiac death, suicide, attempted suicide/self-harm, myocardial infarction, stroke/transient ischaemic attack (TIA), falls, fractures, upper gastrointestinal bleeding, epilepsy/seizures, road traffic accidents, adverse drug reactions and hyponatraemia.Results: In total, 60,746 patients were included in the study cohort. Of these, 54,038 (89.0%) received at least one prescription for an antidepressant during follow-up. The associations with the adverse outcomes were significantly different between the classes of antidepressant drugs for seven outcomes. SSRIs were associated with the highest adjusted hazard ratios (HRs) for falls [1.66, 95% confidence interval (Cl) 1.58 to 1.73] and hyponatraemia (1.52, 95% Cl 1.33 to 1.75), and the group of other antidepressants was associated with the highest HRs for all-cause mortality (1.66, 95% Cl 1.56 to 1.77), attempted suicide/self-harm (5.16, 95% Cl 3.90 to 6.83), stroke/TIA (1.37, 95% Cl 1.22 to 1.55), fracture (1.63, 95% Cl 1.45 to 1.83) and epilepsy/seizures (2.24, 95% CI 1.60 to 3.15) compared with when antidepressants were not being used. TCAs did not have the highest HR for any of the outcomes. There were also significantly different associations between the individual drugs for seven outcomes, with trazodone, mirtazapine and venlafaxine associated with the highest rates for several of these outcomes. The mean incremental cost (for all antidepressant prescriptions) ranged between (sic)51.58 (amitriptyline) and (sic)641.18 (venlafaxine) over the 5-year post-diagnosis period.Conclusions: This study found associations between use of antidepressant drugs and a number of adverse events in older people. There was no evidence that SSRIs or drugs in the group of other antidepressants were associated with a reduced risk of any of the adverse outcomes compared with TCAs; however, they may be associated with an increased risk for certain outcomes. Among individual drugs trazodone, mirtazapine and venlafaxine were associated with the highest rates for some outcomes. Indication bias and residual confounding may explain some of the study findings. The risks of prescribing antidepressants need to be weighed against the potential benefits of these drugs.