Lintunen Jonne, Hamina Aleksi, Lähteenvuo Markku, Paljärvi Tapio, Tanskanen Antti, Tiihonen Jari, Taipale Heidi
Department of Forensic Psychiatry, University of Eastern Finland, Niuvanniemi Hospital, Kuopio, Finland.
Norwegian Centre for Addiction Research (SERAF), Institute of Clinical Medicine, University of Oslo, Oslo, Norway.
Acta Psychiatr Scand. 2025 Jan;151(1):81-91. doi: 10.1111/acps.13762. Epub 2024 Oct 2.
Finding effective treatment regimens for bipolar disorder is challenging, as many patients suffer from significant symptoms despite treatment. This study investigated the risk of relapse (psychiatric hospitalization) and treatment safety (non-psychiatric hospitalization) associated with different doses of antipsychotics and mood stabilizers in persons with bipolar disorder.
Individuals aged 15-65 with bipolar disorder were identified from Finnish national health registers in 1996-2018. Studied antipsychotics included olanzapine, risperidone, quetiapine, aripiprazole; mood stabilizers lithium, valproic acid, lamotrigine, and carbamazepine. Medication use was divided into three time-varying dose categories: low, standard, and high. The studied outcomes were risk of psychiatric hospitalization (relapse) and the risk of non-psychiatric hospitalization (treatment safety). Stratified Cox regression in within-individual design was used.
The cohort included 60,045 individuals (mean age 41.7 years, SD 15.8; 56.4% female). Mean follow-up was 8.3 years (SD 5.8). Of antipsychotics, olanzapine and aripiprazole were associated with a decreased risk of relapse in low and standard doses, and risperidone in low dose. The lowest adjusted hazard ratio (aHR) was observed for standard dose aripiprazole (aHR 0.68, 95% CI 0.57-0.82). Quetiapine was not associated with a decreased risk of relapse at any dose. Mood stabilizers were associated with a decreased risk of relapse in low and standard doses; lowest aHR was observed for standard dose lithium (aHR 0.61, 95% CI 0.56-0.65). Apart from lithium, high doses of antipsychotics and mood stabilizers were associated with an increased risk of non-psychiatric hospitalization. Lithium was associated with a decreased risk of non-psychiatric hospitalization in low (aHR 0.88, 95% CI 0.84-0.93) and standard doses (aHR 0.81, 95% CI 0.74-0.88).
Standard doses of lithium and aripiprazole were associated with the lowest risk of relapse, and standard dose of lithium with the lowest risk of non-psychiatric hospitalization. Quetiapine was not associated with decreased risk of relapse at any dose.
为双相情感障碍找到有效的治疗方案具有挑战性，因为许多患者尽管接受了治疗仍有明显症状。本研究调查了双相情感障碍患者中不同剂量的抗精神病药物和心境稳定剂与复发风险（精神科住院）及治疗安全性（非精神科住院）之间的关系。
从1996 - 2018年芬兰国家健康登记处识别出年龄在15 - 65岁的双相情感障碍患者。研究的抗精神病药物包括奥氮平、利培酮、喹硫平、阿立哌唑；心境稳定剂包括锂盐、丙戊酸、拉莫三嗪和卡马西平。药物使用被分为三个随时间变化的剂量类别：低剂量、标准剂量和高剂量。研究的结局是精神科住院风险（复发）和非精神科住院风险（治疗安全性）。采用个体内设计的分层Cox回归分析。
该队列包括60,045名个体（平均年龄41.7岁，标准差15.8；56.4%为女性）。平均随访时间为8.3年（标准差5.8）。在抗精神病药物中，低剂量和标准剂量的奥氮平和阿立哌唑以及低剂量的利培酮与复发风险降低相关。标准剂量阿立哌唑的调整后风险比（aHR）最低（aHR 0.68，95%置信区间0.57 - 0.82）。喹硫平在任何剂量下均与复发风险降低无关。心境稳定剂在低剂量和标准剂量时与复发风险降低相关；标准剂量锂盐的aHR最低（aHR 0.61，95%置信区间0.56 - 0.65）。除锂盐外，高剂量的抗精神病药物和心境稳定剂与非精神科住院风险增加相关。锂盐在低剂量（aHR 0.88，95%置信区间0.84 - 0.93）和标准剂量（aHR 0.81，95%置信区间0.74 - 0.88）时与非精神科住院风险降低相关。
标准剂量的锂盐和阿立哌唑与最低的复发风险相关，标准剂量的锂盐与最低的非精神科住院风险相关。喹硫平在任何剂量下均与复发风险降低无关。
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