From the Department of Psychiatry, Tri-Service General Hospital.
Student Counseling Center, National Defense Medical Center.
J Clin Psychopharmacol. 2019 Sep/Oct;39(5):472-478. doi: 10.1097/JCP.0000000000001083.
Evidence suggests that atypical antipsychotics (AAPs) exert a short-term mortality risk in people with dementia. We assessed whether additional randomized clinical trials influence the current evidence and the potential effect modifiers.
Electronic databases were systematically searched for randomized controlled trials from their inception through March 2018. A random-effects model was used for analysis. Potential effect modifiers were examined through meta-regression. Trial sequential analysis was performed to quantify the statistical reliability of data in the cumulative meta-analysis with adjustment of significance levels for sparse data and repetitive testing on accumulating data. Certainty of evidence and risk of bias were also evaluated.
We found that compared with placebos, AAPs may increase the risk of mortality (odds ratio [OR], 1.536; 95% confidence intervals [CIs], 1.028-2.296; P = 0.036, high certainty). In the subgroup analysis, the estimated ORs were the highest for olanzapine (1.919; P = 0.232), followed by those for quetiapine (1.663; P = 0.506), aripiprazole (1.649; P = 0.297), and risperidone (1.354; P = 0.277); however, the mortality risk presented by individual AAPs did not exhibit between-group differences. The meta-regression did not identify any effect modifiers, including the chlorpromazine equivalent dose, trial duration, and cognitive status. The trial sequential analysis revealed that future similar trials are unlikely to alter our findings.
Atypical antipsychotics are associated with increased short-term mortality risk, although a disease-drug interaction may contribute to such risk in people with dementia. Patients with dementia may still benefit by AAPs after appropriate assessment of the disease severity as well as the dosage of AAPs, treatment duration, and monitoring of AAPs.
有证据表明，非典型抗精神病药物（AAPs）在痴呆患者中存在短期死亡风险。我们评估了是否有更多的随机临床试验会影响当前的证据和潜在的效应修饰因子。
从研究开始到 2018 年 3 月，系统地检索了电子数据库中的随机对照试验。采用随机效应模型进行分析。通过meta 回归检查潜在的效应修饰因子。进行试验序贯分析，以量化累积荟萃分析中数据的统计可靠性，同时调整稀疏数据的显著性水平，并对累积数据进行重复测试。还评估了证据的确定性和偏倚风险。
与安慰剂相比，AAPs 可能会增加死亡风险（比值比[OR]，1.536；95%置信区间[CI]，1.028-2.296；P=0.036，高度确定性）。在亚组分析中，奥氮平的估计 OR 最高（1.919；P=0.232），其次是喹硫平（1.663；P=0.506）、阿立哌唑（1.649；P=0.297）和利培酮（1.354；P=0.277）；然而，个体 AAPs 表现出的死亡率风险没有组间差异。meta 回归没有发现任何效应修饰因子，包括氯丙嗪等效剂量、试验持续时间和认知状态。试验序贯分析表明，未来类似的试验不太可能改变我们的发现。
非典型抗精神病药物与短期死亡风险增加相关，尽管痴呆患者的疾病-药物相互作用可能导致这种风险。在适当评估疾病严重程度以及 AAPs 的剂量、治疗持续时间和监测 AAPs 后，痴呆患者仍可能从 AAPs 中获益。
