Association of Hydroxylmethyl Glutaryl Coenzyme A Reductase Inhibitors, L-Type Calcium Channel Antagonists, and Biguanides With Rates of Psychiatric Hospitalization and Self-Harm in Individuals With Serious Mental Illness
Association of Hydroxylmethyl Glutaryl Coenzyme A Reductase Inhibitors, L-Type Calcium Channel Antagonists, and Biguanides With Rates of Psychiatric Hospitalization and Self-Harm in Individuals With Serious Mental Illness
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DOI：
10.1001/jamapsychiatry.2018.3907
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发表时间：
2019-04-01
期刊：
影响因子：
25.8
通讯作者：
Dalman, Christina
中科院分区：
文献类型：
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作者：
Hayes, Joseph F.;Lundin, Andreas;Dalman, Christina
药物再利用在精神药物开发中具有潜在的成本效益，低风险和必要性。大量常规数据集的可用性为评估目前使用的药物对严重精神疾病（SMI）患者的益处提供了机会。HMG-CoA RIs、L-型钙通道（LTCC）拮抗剂和双胍类药物与SMI患者减少精神病住院和自我伤害相关。这些对SMI患者进行的个体内队列研究比较了暴露和不暴露于研究药物期间精神病住院和自我伤害的发生率，并对一些随时间变化的协变量进行了调整。参与者包括来自瑞典整个人口的142691名被诊断为双相情感障碍（BPD），精神分裂症或非情感性精神病（NAP）的人，他们年龄在15岁或以上，并在2005年10月1日至2016年12月31日期间接受精神药物治疗。数据分析时间为2018年4月1日至8月31日。干预HMG-CoA RI、LTCC拮抗剂或双胍类药物治疗。主要结局和指标精神病住院和自残入院。结果在142 691名合格参与者中，HMG-CoA RI暴露期与BPD患者精神病住院率降低相关（校正风险比[aHR]，0.86; 95%CI，0.83-0.89; P <0.001），精神分裂症（aHR，0.75; 95% CI，0.71-0.79; P < .001），NAP（aHR，0.80; 95% CI，0.75-0.85; P <0.001），并降低BPD的自我伤害率（aHR，0.76; 95% CI，0.66-0.86; P < .001）和精神分裂症（aHR，0.58; 95% CI，0.45-0.74; P < .001）。在BPD亚组中，LTCC拮抗剂暴露与精神病住院率和自我伤害率降低相关（aHR分别为0.92 [95% CI，0.88-0.96; P < .001]和0.81 [95% CI，0.68-0.95; P = .01]），精神分裂症（aHR分别为0.80 [95%CI，0.74-0.85; P < .001]和0.30 [95%CI，0.18-0.48; P < .001]），NAP（aHR分别为0.89 [95%CI，0.83-0.96; P = .002]和0.56 [95%CI，0.42-0.74; P < .001]）。在双胍暴露期间，BPD亚组的精神病住院率降低（aHR，0.80; 95% CI，0.77-0.84; P < .001），精神分裂症（aHR，0.73; 95% CI，0.69-0.77; P < .001），NAP（aHR，0.85; 95% CI，0.79-0.92; P < .001），BPD患者自我伤害减少（aHR，0.73; 95%CI，0.62-0.84; P < .001）和精神分裂症（aHR，0.64; 95% CI，0.48-0.85;结论和相关性该研究提供了额外的证据，表明暴露于HMG-CoA RI，LTCC拮抗剂，双胍类药物可能改善SMI患者的预后。考虑到这些药物的已知不良事件特征，应将其作为精神症状的再利用药物进行进一步研究。
IMPORTANCE Drug repurposing is potentially cost-effective, low risk, and necessary in psychiatric drug development. The availability of large, routine data sets provides the opportunity to evaluate the potential for currently used medication to benefit people with serious mental illness (SMI).OBJECTIVE To determine whether hydroxylmethyl glutaryl coenzyme A reductase inhibitors (HMG-CoA RIs), L-type calcium channel (LTCC) antagonists, and biguanides are associated with reduced psychiatric hospitalization and self-harm in individuals with SMI.DESIGN, SETTING, AND PARTICIPANTS These within-individual cohort studies of patients with SMI compared rates of psychiatric hospitalization and self-harm during periods of exposure and nonexposure to the study drugs, with adjusting for a number of time-varying covariates. Participants included 142 691 individuals from the entire population of Sweden with a diagnosis of bipolar disorder (BPD), schizophrenia, or nonaffective psychosis (NAP) who were 15 years or older and who were treated with psychiatric medication from October 1, 2005, through December 31, 2016. Data were analyzed from April 1 through August 31, 2018.INTERVENTIONS Treatment with HMG-CoA RIs, LTCC antagonists, or biguanides.MAIN OUTCOMES AND MEASURES Psychiatric hospitalizations and self-harm admissions.RESULTS Among the 142 691 eligible participants, the HMG-CoA RI exposure periods were associated with reduced rates of psychiatric hospitalization in BPD (adjusted hazard ratio [aHR], 0.86; 95% CI, 0.83-0.89; P < .001), schizophrenia (aHR, 0.75; 95% CI, 0.71-0.79; P < .001), and NAP (aHR, 0.80; 95% CI, 0.75-0.85; P < .001) and reduced self-harm rates in BPD (aHR, 0.76; 95% CI, 0.66-0.86; P < .001) and schizophrenia (aHR, 0.58; 95% CI, 0.45-0.74; P < .001). Exposure to LTCC antagonists was associated with reduced rates of psychiatric hospitalization and self-harm in subgroups with BPD (aHRs, 0.92 [95% CI, 0.88-0.96; P < .001] and 0.81 [95% CI, 0.68-0.95; P = .01], respectively), schizophrenia (aHRs, 0.80 [95% CI, 0.74-0.85; P < .001] and 0.30 [95% CI, 0.18-0.48; P < .001], respectively), and NAP (aHRs, 0.89 [95% CI, 0.83-0.96; P = .002] and 0.56 [95% CI, 0.42-0.74; P < .001], respectively). During biguanide exposure, psychiatric hospitalization rates were reduced in subgroups with BPD (aHR, 0.80; 95% CI, 0.77-0.84; P < .001), schizophrenia (aHR, 0.73; 95% CI, 0.69-0.77; P < .001), and NAP (aHR, 0.85; 95% CI, 0.79-0.92; P < .001), and self-harm was reduced in BPD (aHR, 0.73; 95% CI, 0.62-0.84; P < .001) and schizophrenia (aHR, 0.64; 95% CI, 0.48-0.85; P < .001).CONCLUSIONS AND RELEVANCE This study provides additional evidence that exposure to HMG-CoA RIs, LTCC antagonists, and biguanides might lead to improved outcomes for individuals with SMI. Given the well-known adverse event profiles of these agents, they should be further investigated as repurposed agents for psychiatric symptoms.