Antidepressant use and risk of adverse outcomes in older people: population based cohort study.
Antidepressant use and risk of adverse outcomes in older people: population based cohort study.
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DOI：
10.1136/bmj.d4551
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发表时间：
2011-08-02
期刊：
影响因子：
--
通讯作者：
Hippisley-Cox J
中科院分区：
文献类型：
--
作者：
Coupland C;Dhiman P;Morriss R;Arthur A;Barton G;Hippisley-Cox J
目的研究抗抑郁药治疗与老年抑郁症患者几种潜在不良结局风险之间的关系，并按抗抑郁药类别、使用时间和剂量检查风险。研究设计：对65岁及以上被诊断为抑郁症的人群进行队列研究。设置570个一般做法在英国提供数据的QResearch初级保健数据库。研究对象为1996年1月1日至2007年12月31日期间60 746例年龄在65岁至100岁之间的新发抑郁症患者，随访至2008年12月31日。主要结果测量与抗抑郁药使用相关的全因死亡率、自杀未遂/自我伤害、心肌梗死、卒中/短暂性脑缺血发作、福尔斯、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的风险比，校正一系列潜在混杂变量。计算抗抑郁药类别（三环类和相关抗抑郁药、选择性5-羟色胺再摄取抑制剂、其他抗抑郁药）、剂量和使用持续时间以及常用处方药的风险比。结果54038例（89.0%）患者在随访期间接受了至少一种抗抑郁药处方。共开出1 398 359张抗抑郁药处方：选择性5-羟色胺再摄取抑制剂764 659张（54.7%），三环类抗抑郁药442 192张（31.6%），单胺氧化酶抑制剂2203张（0.2%），其他抗抑郁药189 305张（13.5%）。与不良结局的相关性在7种抗抑郁药类别之间存在显著差异。与未使用抗抑郁药时相比，选择性5-羟色胺再摄取抑制剂与福尔斯（1.66，95%置信区间1.58 - 1.73）和低钠血症（1.52，1.33 - 1.75）的最高校正风险比相关。其他抗抑郁药组与全因死亡率的最高校正风险比相关（1.66，1.56至1.77），企图自杀/自我伤害（5.16，3.90 - 6.83），卒中/短暂性脑缺血发作（1.37，1.22至1.55），骨折（1.64，1.46至1.84），癫痫/癫痫发作（2.24，1.60至3.15），与未使用抗抑郁药时相比。三环类抗抑郁药对任何结果的风险比都不是最高的。对于相同的7种结局，个体药物之间也存在显著不同的相关性;曲唑酮（三环类抗抑郁药）、米氮平和文拉法辛（均在其他抗抑郁药组中）与其中一些结局的发生率最高相关。未服用抗抑郁药的患者1年内全因死亡的绝对风险为7.04%，服用三环类抗抑郁药的患者为8.12%，服用选择性5-羟色胺再摄取抑制剂的患者为10.61%，服用其他抗抑郁药的患者为11.43%。结论与三环类抗抑郁药相比，选择性5-羟色胺再摄取抑制剂和其他抗抑郁药组的药物与几种不良结局的风险增加相关。在单个药物中，曲唑酮、米氮平和文拉法辛与某些结局的最高风险相关。由于这是一项观察性研究，因此容易受到适应症、渠道偏倚和残留混杂因素的干扰，因此处方不同抗抑郁药物的患者之间的特征差异可能仍然存在，这些差异可能解释药物与不良结局之间的某些相关性。需要进一步的研究来证实这些发现，但是当这些药物被开给老年人时，应该仔细评估不同抗抑郁药的风险和益处。
Objectives To investigate the association between antidepressant treatment and risk of several potential adverse outcomes in older people with depression and to examine risks by class of antidepressant, duration of use, and dose. Design Cohort study of people aged 65 and over diagnosed as having depression. Setting 570 general practices in the United Kingdom supplying data to the QResearch primary care database. Participants 60 746 patients diagnosed as having a new episode of depression between the ages of 65 and 100 years from 1 January 1996 to 31 December 2007 and followed up until 31 December 2008. Main outcome measures Hazard ratios associated with antidepressant use for all cause mortality, attempted suicide/self harm, myocardial infarction, stroke/transient ischaemic attack, falls, fractures, upper gastrointestinal bleeding, epilepsy/seizures, road traffic accidents, adverse drug reactions, and hyponatraemia, adjusted for a range of potential confounding variables. Hazard ratios were calculated for antidepressant class (tricyclic and related antidepressants, selective serotonin reuptake inhibitors, other antidepressants), dose, and duration of use and for commonly prescribed individual drugs. Results 54 038 (89.0%) patients received at least one prescription for an antidepressant during follow-up. A total of 1 398 359 antidepressant prescriptions were issued: 764 659 (54.7%) for selective serotonin reuptake inhibitors, 442 192 (31.6%) for tricyclic antidepressants, 2203 (0.2%) for monoamine oxidase inhibitors, and 189 305 (13.5%) for the group of other antidepressants. The associations with the adverse outcomes differed significantly between the antidepressant classes for seven outcomes. Selective serotonin reuptake inhibitors were associated with the highest adjusted hazard ratios for falls (1.66, 95% confidence interval 1.58 to 1.73) and hyponatraemia (1.52, 1.33 to 1.75) compared with when antidepressants were not being used. The group of other antidepressants was associated with the highest adjusted hazard ratios for all cause mortality (1.66, 1.56 to 1.77), attempted suicide/self harm (5.16, 3.90 to 6.83), stroke/transient ischaemic attack (1.37, 1.22 to 1.55), fracture (1.64, 1.46 to 1.84), and epilepsy/seizures (2.24, 1.60 to 3.15), compared with when antidepressants were not being used. Tricyclic antidepressants did not have the highest hazard ratio for any of the outcomes. Significantly different associations also existed between the individual drugs for the same seven outcomes; trazodone (tricyclic antidepressant), mirtazapine, and venlafaxine (both in the group of other antidepressants) were associated with the highest rates for some of these outcomes. Absolute risks over 1 year for all cause mortality were 7.04% for patients while not taking antidepressants, 8.12% for those taking tricyclic antidepressants, 10.61% for selective serotonin reuptake inhibitors, and 11.43% for other antidepressants. Conclusions Selective serotonin reuptake inhibitors and drugs in the group of other antidepressants were associated with an increased risk of several adverse outcomes compared with tricyclic antidepressants. Among individual drugs, trazodone, mirtazapine, and venlafaxine were associated with the highest risks for some outcomes. As this is an observational study, it is susceptible to confounding by indication, channelling bias, and residual confounding, so differences in characteristics between patients prescribed different antidepressant drugs that could account for some of the associations between the drugs and the adverse outcomes may remain. Further research is needed to confirm these findings, but the risks and benefits of different antidepressants should be carefully evaluated when these drugs are prescribed to older people.
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