Real-world Effectiveness of Pharmacologic Treatments for the Prevention of Rehospitalization in a Finnish Nationwide Cohort of Patients With Bipolar Disorder
Real-world Effectiveness of Pharmacologic Treatments for the Prevention of Rehospitalization in a Finnish Nationwide Cohort of Patients With Bipolar Disorder
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DOI：
10.1001/jamapsychiatry.2017.4711
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发表时间：
2018-04-01
期刊：
影响因子：
25.8
通讯作者：
Tiihonen, Jari
中科院分区：
文献类型：
--
作者：
Lahteenvuo, Markku;Tanskanen, Antti;Tiihonen, Jari
重要性情绪稳定剂和抗精神病药物是双相情感障碍的主要维持治疗方法。锂被认为是最有效的情绪稳定剂，但人们对与特定治疗相关的总体健康结果以及特定精神药物或给药途径在防止再次住院方面的比较长期有效性知之甚少。目的研究在全国范围内的双相情感障碍患者队列中，药物治疗在防止再次住院方面的比较有效性。设计、设置和参与者这项队列研究调查了1987年1月1日至2012年12月31日期间所有因双相情感障碍住院的芬兰患者中精神、心血管和所有原因住院的风险(N=18018；平均随访时间为7.2年)，使用前瞻性收集的全国住院和配药数据库。主要的分析是个体内分析，其中每个个体被用作他或她自己的对照，以消除选择偏见。这项研究调整了伴随的精神药物的效果、病程以及暴露和非暴露的时间顺序。统计分析1996年1月1日至2012年12月31日的数据。结果队列中9558名女性和8460名男性，平均年龄46.6[17.0]岁，9721名患者(54.0%)至少有1次精神科再住院。在使用和不使用具有名义统计学意义的特定药物之间的比较中，利培酮长效注射剂(HR，0.58[95%CI，0.34~1.00])、加巴喷丁(HR，0.58[95%CI，0.44~0.77])、奋乃静长效注射剂(HR，0.60[95%CI，0.41~0.88])和碳酸锂(HR，0.67[95%CI，0.60~0.73])与精神疾病再住院的风险最低。在全原因住院方面，锂(HR，0.71[95%CI，0.66-0.76])与最低风险相关。最常用的抗精神病药物富马酸奎硫平仅显示出温和的疗效(精神科再住院的风险：HR，0.92[95%CI，0.85-0.98]；全原因住院的风险：HR，0.93[95%CI，0.88-0.98])。与相同的口服抗精神病药物(精神科再住院风险：HR，0.70[95%CI，0.55-0.90]；全原因住院风险：HR，0.70[95%CI，0.57-0.86])相比，长效注射与显著更好的结果相关。敏感性分析结果显示，与口服相比，锂和长效注射剂的益处一致。结论和相关性锂是最有效的情绪稳定剂，长效注射剂是最有效的抗精神病药物，在预防因精神或身体疾病而住院方面是最有效的。
IMPORTANCE Mood stabilizers and antipsychotics are the main maintenance treatments for bipolar disorder. Lithium is considered to be the most effective mood stabilizer, but very little is known about overall health outcomes associated with specific treatments and the comparative long-term effectiveness of specific psychotropics or routes of administration in the prevention of rehospitalizations.OBJECTIVE To study the comparative effectiveness of pharmacologic treatments in the prevention of rehospitalization in a nationwide cohort of patients with bipolar disorder.DESIGN, SETTING, AND PARTICIPANTS This cohort study examined the risk of psychiatric, cardiovascular, and all-cause hospitalization from January 1, 1987, to December 31, 2012, among all patients in Finland who had been hospitalized for bipolar disorder (N = 18 018; mean follow-up time, 7.2 years) using prospectively gathered nationwide databases for hospitalization and dispensed medications. The primary analysis was within-individual analysis, in which each individual was used as his or her own control to eliminate selection bias. The study adjusted for the effect of concomitant psychotropic medications, duration of illness, and the temporal orders of exposure and nonexposure periods. Statistical analysis was conducted from January 1, 1996, to December 31, 2012.MAIN OUTCOMES AND MEASURES Adjusted hazard ratios (HRs) for rehospitalization were calculated.RESULTS Among the cohort (9558 women and 8460 men; mean [SD] age, 46.6 [17.0] years), 9721 patients (54.0%) had at least 1 psychiatric rehospitalization. In comparison between use and no use among specific agents reaching nominal statistical significance, risperidone long-acting injection (HR, 0.58 [95% CI, 0.34-1.00]), gabapentin (HR, 0.58 [95% CI, 0.44-0.77]), perphenazine long-acting injection (HR, 0.60 [95% CI, 0.41-0.88]), and lithium carbonate (HR, 0.67 [95% CI, 0.60-0.73]) were associated with the lowest risk of psychiatric rehospitalization. Concerning all-cause hospitalization, lithium (HR, 0.71 [95% CI, 0.66-0.76]) was associated with the lowest risk. The most frequently used antipsychotic treatment, quetiapine fumarate, showed only modest effectiveness (risk of psychiatric rehospitalization: HR, 0.92 [95% CI, 0.85-0.98]; risk of all-cause hospitalization: HR, 0.93 [95% CI, 0.88-0.98]). Long-acting injections were associated with substantially better outcomes compared with identical oral antipsychotics (risk of psychiatric rehospitalization: HR, 0.70 [95% CI, 0.55-0.90]; risk of all-cause hospitalization: HR, 0.70 [95% CI, 0.57-0.86]). Results from sensitivity analyses showed consistent beneficial effects only for lithium and for long-acting injections compared with their oral counterparts.CONCLUSIONS AND RELEVANCE Lithium was the most effective mood stabilizer, and long-acting injections the most effective antipsychotics, in preventing hospitalization due to mental or physical illness.