Dosing levels of antipsychotics and mood stabilizers in bipolar disorder: A Nationwide cohort study on relapse risk and treatment safety.

IF 5.3 2区医学 Q1 PSYCHIATRY Acta Psychiatrica Scandinavica Pub Date : 2024-10-02 DOI:10.1111/acps.13762

Jonne Lintunen, Aleksi Hamina, Markku Lähteenvuo, Tapio Paljärvi, Antti Tanskanen, Jari Tiihonen, Heidi Taipale

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Abstract

Background: 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.

Methods: 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.

Results: 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).

Conclusions: 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.

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双相情感障碍中抗精神病药物和情绪稳定剂的剂量水平：关于复发风险和治疗安全性的全国队列研究。

背景：寻找双相情感障碍的有效治疗方案具有挑战性，因为许多患者尽管接受了治疗，但仍有明显的症状。本研究调查了与双相情感障碍患者不同剂量的抗精神病药物和情绪稳定剂相关的复发风险（精神病住院）和治疗安全性（非精神病住院）：方法：从1996年至2018年芬兰全国健康登记册中识别出15至65岁的躁郁症患者。研究的抗精神病药物包括奥氮平、利培酮、喹硫平、阿立哌唑；情绪稳定剂包括锂、丙戊酸、拉莫三嗪和卡马西平。药物使用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。研究结果包括精神病住院风险（复发）和非精神病住院风险（治疗安全性）。研究采用了个体内部设计的分层考克斯回归法：队列中包括 60,045 人（平均年龄 41.7 岁，SD 15.8；56.4% 为女性）。平均随访时间为 8.3 年（SD 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与降低复发风险有关，低剂量的利培酮与降低复发风险有关。标准剂量阿立哌唑的调整后危险比（aHR）最低（aHR 0.68，95% CI 0.57-0.82）。无论采用何种剂量，喹硫平都不会降低复发风险。低剂量和标准剂量的情绪稳定剂与复发风险降低有关；标准剂量锂的aHR最低（aHR 0.61，95% CI 0.56-0.65）。除了锂以外，高剂量的抗精神病药物和情绪稳定剂与非精神病住院风险的增加有关。低剂量（aHR 0.88，95% CI 0.84-0.93）和标准剂量（aHR 0.81，95% CI 0.74-0.88）的锂与非精神病住院风险的降低有关：结论：标准剂量的锂和阿立哌唑与最低的复发风险相关，标准剂量的锂与最低的非精神病住院风险相关。任何剂量的喹硫平都不会降低复发风险。

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来源期刊

Acta Psychiatrica Scandinavica 医学-精神病学

CiteScore

11.20

自引率

3.00%

发文量

135

审稿时长

6-12 weeks

期刊介绍： Acta Psychiatrica Scandinavica acts as an international forum for the dissemination of information advancing the science and practice of psychiatry. In particular we focus on communicating frontline research to clinical psychiatrists and psychiatric researchers. Acta Psychiatrica Scandinavica has traditionally been and remains a journal focusing predominantly on clinical psychiatry, but translational psychiatry is a topic of growing importance to our readers. Therefore, the journal welcomes submission of manuscripts based on both clinical- and more translational (e.g. preclinical and epidemiological) research. When preparing manuscripts based on translational studies for submission to Acta Psychiatrica Scandinavica, the authors should place emphasis on the clinical significance of the research question and the findings. Manuscripts based solely on preclinical research (e.g. animal models) are normally not considered for publication in the Journal.