New study evaluates real-world effectiveness of bipolar disorder treatments

Bipolar disorder is a chronic psychiatric condition that requires long-term treatment to prevent relapse and hospitalization. While clinical guidelines recommend mood stabilizers and antipsychotics, either alone or in combination, most of this evidence comes from randomized controlled trials. These trials often exclude patients with complex conditions, making it difficult to understand how treatments perform in routine clinical practice.

Now, in a new study published online on 30 April, 2026, in The British Journal of Psychiatry, researchers from Japan have addressed this gap using real-world data. The study was led by Professor Tadafumi Kato from the Department of Psychiatry and Behavioral Science at Juntendo University Graduate School of Medicine, Japan, along with Dr. Yasuyuki Okumura from the Initiative for Clinical Epidemiological Research, Japan. By analyzing nationwide health data, the team evaluated how different treatment strategies influence the risk of psychiatric hospitalization in patients with bipolar disorder.

“We used real-world data to systematically evaluate how existing medications perform in routine clinical practice,” explains Prof. Kato. “Our goal was to identify treatment patterns associated with better outcomes, particularly in reducing the risk of hospitalization.”

To conduct the study, the researchers used Japan’s National Database of Health Insurance Claims and Specific Health Checkups, one of the largest healthcare databases globally. The analysis included 315,046 adults diagnosed with bipolar disorder and followed them for a median period of over seven years. Importantly, the study used a within-individual design, meaning each patient served as their own control. This approach helps reduce bias by comparing outcomes during different treatment periods among patients with bipolar disorder. The researchers conducted separate analyses to evaluate treatment effectiveness. Periods of monotherapy were compared with periods of nonuse of the respective medications, while periods of combination therapy were compared with periods of monotherapy. The main outcome was psychiatric hospitalization, which reflects relapse or worsening of the condition.

The results showed that several mood stabilizers, including lithium, valproate, lamotrigine, and carbamazepine, were associated with a lower risk of hospitalization compared with periods when these medications were not used. Among antipsychotics, drugs such as aripiprazole and zotepine were also linked to reduced hospitalization risk, although the effectiveness varied across agents. Importantly, some combination therapies were associated with additional reductions in hospitalization risk compared with monotherapy. For example, combinations such as lithium with carbamazepine, aripiprazole, or valproate were associated with further reductions in hospitalization risk compared with lithium alone. These findings suggest that combining medications may enhance treatment effectiveness in certain patients.

“Our findings suggest that some combination therapies may offer added protection against relapse compared with monotherapy,” says Prof. Kato. “This could be especially relevant for patients who do not respond to monotherapies.”

The study also highlighted differences in effectiveness between medications. Lithium showed strong and consistent associations with reduced hospitalization risk, supporting its role as a cornerstone treatment for bipolar disorder. At the same time, the results suggest that not all antipsychotics provide equal benefit, emphasizing the importance of selecting appropriate treatment combinations.

Another notable aspect of the study is its scale. By using nationwide data from Japan’s universal health insurance system, the researchers were able to capture treatment patterns across a large and diverse population. This provides a more comprehensive picture of how therapies perform in real-world settings.

“The scale of this study demonstrates the value of Japan’s national health database for generating clinically meaningful evidence,” Prof. Kato notes. “We believe such data can support the development of better treatment strategies and contribute to clinical guidelines.”

These findings have important implications for both clinicians and policymakers. They provide practical insights into how different treatment strategies may influence long-term outcomes, particularly the risk of hospitalization. At the same time, the authors caution that treatment decisions should remain individualized, taking into account potential side effects and patient-specific factors.

Overall, this study offers real-world evidence on the effectiveness of pharmacological treatments for bipolar disorder. By systematically comparing mono- and combination therapies at an unprecedented scale, it helps bridge the gap between clinical trials and everyday practice, bringing us closer to more informed and personalized care.

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Reference
Authors: Yasuyuki Okumura¹, Hidetaka Tamune², Hiroyuki Harada², Tadafumi Kato²*
DOI: 10.1192/bjp.2026.10636
Affiliations:
¹ Initiative for Clinical Epidemiological Research, Japan
² Department of Psychiatry and Behavioral Science, Juntendo University Graduate School of Medicine, Japan

About Professor Tadafumi Kato from Department of Psychiatry and Behavioral Science, Japan
Dr. Tadafumi Kato, MD, PhD, is a Professor at the Department of Psychiatry and Behavioral Science at Juntendo University Graduate School of Medicine, Japan, and Director of the Center for Mood Disorders. With over 36 years of research experience, he has authored more than 360 peer-reviewed publications (h-index: 73). His research focuses on the neurobiology of bipolar disorder, including genomics, mitochondrial dysfunction, neuroimaging, and mood stabilizer development.


History of Juntendo University
Juntendo was originally founded in 1838 as a school of Dutch medicine at a time when Western medical education was not yet embedded as a normal part of Japanese society. With the creation of Juntendo, the founders hoped to create a place where people could come together with the shared goal of helping society through the powers of medical education and practices. Their aspirations led to the establishment of Juntendo Hospital, the first private hospital in Japan among those continuously operating. Through the years, the institution's experience and perspective as an institution of higher education and a place of clinical practice has enabled Juntendo University to play an integral role in the shaping of Japanese medical education and practices. Along the way, the focus of the institution has also expanded, now consisting of nine undergraduate programs and six graduate programs; the university specializes in the fields of health science, health and sports science, nursing health care and sciences, and international liberal arts, as well as medicine. Today, Juntendo University continues to pursue innovative approaches to international level education and research with the goal of applying the results to society.

Mission Statement
The mission of Juntendo University is to strive for advances in society through education, research, and healthcare, guided by the motto “Jin – I exist as you exist” and the principle of “Fudan Zenshin - Continuously Moving Forward.” The spirit of “Jin,” which is the ideal of all those who gather at Juntendo University, entails being kind and considerate of others. The principle of “Fudan Zenshin” conveys the belief of the founders that education and research activities will only flourish in an environment of free competition. Our academic environment enables us to educate outstanding students to become healthcare professionals patients can believe in, scientists capable of innovative discoveries and inventions, and global citizens ready to serve society.