Cognitive impairment, including decreased attention and memory, remains one of the most disabling aspects of schizophrenia, affecting social life of patients. However, no effective treatment has yet been established for it. Now, researchers have investigated the effect of adding brexpiprazole on cognitive function in patients with schizophrenia. The findings revealed that patients with schizophrenia receiving adjunctive brexpiprazole showed a meaningful improvement in information processing speed, without worsening psychiatric symptoms.
Schizophrenia is a complex psychiatric disorder characterized by positive symptoms such as hallucinations and delusions and negative symptoms including emotional flattening, social withdrawal, and reduced motivation. Beyond these clinical features, cognitive dysfunction is a core and persistent challenge. Approximately 75–85% of patients with schizophrenia experience impairments in attention, memory, processing speed, and executive function. These deficits have a greater impact on daily functioning and social participation than positive or negative symptoms, making cognition a critical yet insufficiently addressed treatment target.
Cognitive dysfunction contributes significantly to unemployment and social disengagement, affecting nearly 80% of patients. Atypical antipsychotics are generally preferred for schizophrenia due to their relatively favorable cognitive profiles. Among them, brexpiprazole (BRX) has a distinctive pharmacological profile. It acts as a partial agonist of dopamine D2 and serotonin 5-HT1A receptors while antagonizing serotonin 5-HT2A,7 receptors. These properties differentiate BRX from other antipsychotics and have been linked to potential cognitive benefits. While BRX monotherapy may improve cognitive and social functioning, its effects as an adjunct to ongoing antipsychotic treatment had not been clearly established.
To elucidate this, a research team led by Professor Hiroyuki Kamei and graduate student Mr. Yuma Shimizu from the Office of Clinical Pharmacy Practice and Health Care Management, Meijo University, Japan, along with Dr. Ippei Takeuchi from the Office of Clinical Pharmacy Practice and Health Care Management, Meijo University, and Department of Psychiatry, Okehazama Hospital, Japan; Dr. Manako Hanya from the Office of Clinical Pharmacy Practice and Health Care Management, Meijo University; and Dr. Kiyoshi Fujita from the Department of Psychiatry, Okehazama Hospital, Japan, conducted an observational study examining the effects of additional administration of BRX on cognitive function in schizophrenia. The study was made available online on November 18, 2025, and was published in Volume 11, Issue 17 of Heliyon journal on December 1, 2025.
The motivation behind the research stems from a major therapeutic gap. Prof. Kamei explains,
"Cognitive impairments in schizophrenia constitute a major barrier to social participation. However, effective treatment remains unestablished."
The researchers conducted an observational study examining the effects of adding BRX to existing antipsychotic regimens in patients with schizophrenia and prominent negative symptoms. Nineteen outpatients aged 18–65 years with a negative score of 20 or higher on the Positive and Negative Syndrome Scale (PANSS) scores were enrolled after excluding individuals with conditions that could affect cognitive assessment. BRX was administered alongside ongoing treatments, including multi-acting receptor-targeted antipsychotics, serotonin-dopamine antagonists, or dopamine partial agonists. Cognitive function was assessed using the trail making test (TMT) and word fluency test, while psychiatric symptoms were measured with PANSS at baseline and after 4, 8, and 16 weeks.
The study demonstrated a significant improvement in information processing speed, as measured by TMT-A, at all follow-up points after BRX administration. Other cognitive measures showed modest but non-significant changes. Notably, cognitive improvement occurred independently of changes in psychiatric symptom severity, indicating a direct effect of BRX.
These findings suggest that BRX may serve as a valuable adjunctive therapy for improving cognitive function, particularly processing speed, without destabilizing psychiatric symptoms. Although the study was limited by a small sample size and an uncontrolled design, it provides important preliminary evidence.
"Additional administration of BRX for 16 weeks in patients with schizophrenia significantly improved attention and information processing speed. Thus, our study demonstrates that BRX has significant potential to contribute to the future development of psychiatric treatment," says Prof. Kamei.
Overall, adjunctive BRX shows promise as a strategy to attenuate cognitive dysfunction in schizophrenia. These results support further investigation through larger, controlled studies, and reinforce the importance of targeting cognitive outcomes to improve long-term functional recovery in schizophrenia.
"Our pioneering research aims to enhance the quality of psychiatric care and strengthen and expand the professional role of pharmacists," concludes Mr. Shimizu.
About Meijo University
Meijo University traces its origin back to the establishment of the Nagoya Science and Technology Course in 1926, giving it a proud history of more than 90 years. As one of the largest universities in the Chubu region, Meijo University is a comprehensive learning institution that supports a wide range of academic fields from the humanities to physical sciences. With a network of more than 200,000 graduates and alumni, it strives to contribute not only to local industries but also to international communities in various fields. Meijo University is also known as the birthplace of the carbon nanotube. To foster the human resources of the next generation, the university continues to tackle ongoing challenges by further enhancing its campus and creating new faculties.
Website: https://www.meijo-u.ac.jp/english/
About Professor Hiroyuki Kamei from Meijo University
Dr. Hiroyuki Kamei is a Professor at the Office of Clinical Pharmacy Practice and Health Care Management, Meijo University, Japan. He received his Bachelor of Science in Pharmacy from Meijo University in 1984 and Doctor of Pharmaceutical Sciences from Meijo University in 1997. He has authored around 175 peer-reviewed publications in clinical psychopharmacology, neuropsychopharmacology, and psychiatric disorders. His research focuses on mental health pharmacotherapy, cognitive function evaluation in schizophrenia, and pharmacist–patient communication.
About Mr. Yuma Shimizu from Meijo University
Mr. Yuma Shimizu is a graduate student at the Office of Clinical Pharmacy Practice and Health Care Management, Meijo University, Japan. His research focuses on clinical pharmacy and clinical psychopharmacology.
Funding information
The present study was supported by JSPS KAKENHI, Grant Number JP23K06243 (Japan). The funder had no involvement in the study design; in the collection, analysis, and interpretation of data; in the writing of the manuscript; or in the decision to submit the article for publication.
