Antipsychotics, other psychotropics, and the risk of death in patients with dementia: number needed to harm.
Antipsychotics, other psychotropics, and the risk of death in patients with dementia: number needed to harm.
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DOI：
10.1001/jamapsychiatry.2014.3018
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发表时间：
2015-05
期刊：
影响因子：
25.8
通讯作者：
Kales, Helen C.
中科院分区：
文献类型：
--
作者：
Maust, Donovan T.;Kim, Hyungjin Myra;Seyfried, Lisa S.;Chiang, Claire;Kavanagh, Janet;Schneider, Lon S.;Kales, Helen C.
抗精神病药物与老年痴呆症患者死亡率增加相关，但相对于不治疗或替代精神药物，其对风险的绝对影响尚不清楚。确定痴呆患者使用抗精神病药、丙戊酸及其衍生物和抗抑郁药相对于不治疗或抗抑郁药治疗的绝对死亡风险增加和需要伤害的人数（NNH）（即，接受与1例死亡相关的治疗的患者人数）。一项回顾性病例对照研究于1998年10月1日至2009年9月30日在退伍军人健康管理局进行。参与者包括90786名65岁或以上的痴呆症患者。最终分析于2014年8月进行。抗精神病药（氟哌啶醇、奥氮平、奎替鲁和利培酮）、丙戊酸及其衍生物或抗抑郁药的新处方（46 008名药物使用者）。在180天的随访中，药物使用者与非药物使用者在几个危险因素上相匹配的死亡风险和NNH的绝对变化。在开始药物治疗的患者中，还使用抗抑郁药组作为参考，调整年龄，性别，痴呆年数，谵妄的存在以及其他临床和人口统计学特征，比较与每种药物相关的死亡风险。次要分析比较了奥氮平、奎替鲁和利培酮剂量调整后死亡风险的绝对变化。与相应匹配的非使用者相比，接受氟哌啶醇的个体死亡风险增加3.8%（95% CI，1.0%-6.6%; P < .01），NNH为26（95% CI，15-99）;其次是利培酮，3.7%（95% CI，2.2%-5.3%; P < .01），NNH为27（95% CI，19-46）;奥氮平，2.5%（95% CI，0.3%-4.7%; P = .02），NNH为40（95% CI，21-312）;喹替利嗪，2.0%（95% CI，0.7%-3.3%; P < .01），NNH为50（95% CI，30-150）。与抗抑郁药使用者相比，氟哌啶醇使用者的死亡风险范围为12.3%（95%CI，8.6%-16.0%; P < .01），NNH为8（95%CI，6-12），而喹替利嗪使用者的死亡风险范围为3.2%（95%CI，1.6%-4.9%; P < .01），NNH为31（95%CI，21-62）。作为一个组，非典型抗精神病药（奥氮平、奎替鲁和利培酮）显示死亡风险的剂量反应增加，高剂量亚组的死亡率比低剂量组高3.5%（95%CI，0.5%-6.5%; P = 0.02）。与奎替鲁肽直接比较时，利培酮（1.7%; 95%CI，0.6%-2.8%; P = 0.003）和奥氮平（1.5%; 95%CI，0.02%-3.0%; P = 0.047）的剂量校正死亡风险均增加。抗精神病药物对老年痴呆患者死亡率的绝对影响可能高于以前的报道，并随剂量增加而增加。
Antipsychotic medications are associated with increased mortality in older adults with dementia, yet their absolute effect on risk relative to no treatment or an alternative psychotropic is unclear. To determine the absolute mortality risk increase and number needed to harm (NNH) (ie, number of patients who receive treatment that would be associated with 1 death) of antipsychotic, valproic acid and its derivatives, and antidepressant use in patients with dementia relative to either no treatment or antidepressant treatment. A retrospective case-control study was conducted in the Veterans Health Administration from October 1, 1998, through September 30, 2009. Participants included 90 786 patients 65 years or older with a diagnosis of dementia. Final analyses were conducted in August 2014. A new prescription for an antipsychotic (haloperidol, olanzapine, quetiapine, and risperidone), valproic acid and its derivatives, or an antidepressant (46 008 medication users). Absolute change in mortality risk and NNH over 180 days of follow-up in medication users compared with nonmedication users matched on several risk factors. Among patients in whom a treatment with medication was initiated, mortality risk associated with each agent was also compared using the antidepressant group as the reference, adjusting for age, sex, years with dementia, presence of delirium, and other clinical and demographic characteristics. Secondary analyses compared dose-adjusted absolute change in mortality risk for olanzapine, quetiapine, and risperidone. Compared with respective matched nonusers, individuals receiving haloperidol had an increased mortality risk of 3.8% (95% CI, 1.0%–6.6%; P < .01) with an NNH of 26 (95% CI, 15–99); followed by risperidone, 3.7% (95% CI, 2.2%–5.3%; P < .01) with an NNH of 27 (95% CI, 19–46); olanzapine, 2.5% (95% CI, 0.3%–4.7%; P = .02) with an NNH of 40 (95% CI, 21–312); and quetiapine, 2.0% (95% CI, 0.7%–3.3%; P < .01) with an NNH of 50 (95% CI, 30–150). Compared with antidepressant users, mortality risk ranged from 12.3% (95% CI, 8.6%–16.0%; P < .01) with an NNH of 8 (95% CI, 6–12) for haloperidol users to 3.2% (95% CI, 1.6%–4.9%; P < .01) with an NNH of 31 (95% CI, 21–62) for quetiapine users. As a group, the atypical antipsychotics (olanzapine, quetiapine, and risperidone) showed a dose-response increase in mortality risk, with 3.5% greater mortality (95% CI, 0.5%–6.5%; P = .02) in the high-dose subgroup relative to the low-dose group. When compared directly with quetiapine, dose-adjusted mortality risk was increased with both risperidone (1.7%; 95% CI, 0.6%–2.8%; P = .003) and olanzapine (1.5%; 95% CI, 0.02%–3.0%; P = .047). The absolute effect of antipsychotics on mortality in elderly patients with dementia may be higher than previously reported and increases with dose.
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影响因子：
14.6
作者：
Schneeweiss, Sebastian;Setoguchi, Soko;Wang, Philip S.
通讯作者：
Wang, Philip S.
影响因子：
158.5
作者：
Devanand, D. P.;Mintzer, Jacobo;Levin, Bruce
通讯作者：
Levin, Bruce
影响因子：
17.7
作者：
Kales, Helen C.;Valenstein, Marcia;Blow, Frederic C.
通讯作者：
Blow, Frederic C.
DOI：
10.1136/bmj.e977
发表时间：
2012-02-23
期刊：
BMJ (Clinical research ed.)
影响因子：
--
作者：
Huybrechts KF;Gerhard T;Crystal S;Olfson M;Avorn J;Levin R;Lucas JA;Schneeweiss S
通讯作者：
Schneeweiss S
影响因子：
10.6
作者：
Andreasen, Nancy C.;Pressler, Marcus;Nopoulos, Peg;Miller, Del;Ho, Beng-Choon
通讯作者：
Ho, Beng-Choon