Department of Forensic Psychiatry, University of Eastern Finland, Niuvanniemi Hospital, Kuopio, Finland.
Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden.
JAMA Psychiatry. 2018 Apr 1;75(4):347-355. doi: 10.1001/jamapsychiatry.2017.4711.
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.
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.
Adjusted hazard ratios (HRs) for rehospitalization were calculated.
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.
Lithium was the most effective mood stabilizer, and long-acting injections the most effective antipsychotics, in preventing hospitalization due to mental or physical illness.
心境稳定剂和抗精神病药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心境稳定剂，但对于特定治疗与特定精神药物或给药途径在预防再入院方面的整体健康结果以及长期有效性，我们知之甚少。
在全国范围内的双相情感障碍患者队列中，研究药物治疗预防再入院的比较效果。
设计、地点和参与者：这项队列研究使用前瞻性收集的全国住院和处方药物数据库，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（N=18018；平均随访时间为 7.2 年）的精神科、心血管和全因住院风险。主要分析是个体内分析，每个个体都被用作自己的对照，以消除选择偏倚。该研究调整了伴随精神药物治疗、疾病持续时间以及暴露和非暴露期的时间顺序的影响。统计分析于 1996 年 1 月 1 日至 2012 年 12 月 31 日进行。
计算了再入院的调整后危险比（HR）。
在队列中（9558 名女性和 8460 名男性；平均[SD]年龄为 46.6[17.0]岁），9721 名患者（54.0%）至少有 1 次精神科再入院。在达到名义统计学显著性的特定药物使用与不使用之间的比较中，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]）、长效苯丙嗪（HR，0.60[95%CI，0.41-0.88]）和碳酸锂（HR，0.67[95%CI，0.60-0.73]）与最低精神科再入院风险相关。关于全因住院，锂（HR，0.71[95%CI，0.66-0.76]）与最低风险相关。最常使用的抗精神病药物富马酸喹硫平仅显示出适度的效果（精神科再入院风险：HR，0.92[95%CI，0.85-0.98]；全因住院风险：HR，0.93[95%CI，0.88-0.98]）。长效注射剂与相同的口服抗精神病药物相比，具有显著更好的效果（精神科再入院风险：HR，0.70[95%CI，0.55-0.90]；全因住院风险：HR，0.70[95%CI，0.57-0.86]）。敏感性分析的结果表明，锂和长效注射剂与它们的口服对应物相比，仅对精神和身体疾病的住院治疗具有有益的效果。
锂是最有效的心境稳定剂，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导致的住院。
