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.

重要性 情绪稳定剂和抗精神病药是双相情感障碍的主要维持治疗。锂被认为是最有效的情绪稳定剂，但对于与特定治疗相关的整体健康结果以及特定精神药物或给药途径在预防再住院方面的相对长期有效性知之甚少。

目的 在全国范围的双相情感障碍患者队列中研究药物治疗在预防再住院方面的比较效果。

设 _ 018；平均随访时间，7.2 年）使用前瞻性收集的全国范围内的住院和配药数据库。主要分析是个体内分析，其中每个人都被用作他或她自己的对照以消除选择偏差。该研究调整了伴随的精神药物的影响、疾病持续时间以及暴露和非暴露期的时间顺序。统计分析于 1996 年 1 月 1 日至 2012 年 12 月 31 日进行。

主要结果和措施 计算了再住院的调整后风险比 (HRs)。

结果 在队列中（9558 名女性和 8460 名男性；平均 [SD] 年龄，46.6 [17.0] 岁），9721 名患者（54.0%）至少有 1 次精神病再住院。在达到标称统计学意义的特定药物中，利培酮长效注射液（HR，0.58 [95% CI，0.34-1.00]）、加巴喷丁（HR，0.58 [95% CI，0.44-0.77]）的使用与未使用比较, 奋乃静长效注射液 (HR, 0.60 [95% CI, 0.41-0.88]) 和碳酸锂 (HR, 0.67 [95% CI, 0.60-0.73]) 与最低的精神病再住院风险相关。关于全因住院，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喹硫平仅显示出适度的有效性（精神病再住院风险：HR，0.92 [95% CI，0.85-0.98]；全因住院风险：HR，0.93 [95% CI，0.88-0.98]）。与相同的口服抗精神病药相比，长效注射与显着更好的结果相关（精神病再住院风险：HR，0.70 [95% CI，0.55-0.90]；全因住院风险：HR，0.70 [95% CI，0.57 -0.86]）。敏感性分析的结果显示，与口服药物相比，仅锂和长效注射剂具有一致的有益效果。

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，可预防因精神或身体疾病住院。