Diseases of the central nervous system include schizophrenia, depression, bipolar disorder, and Alzheimer's disease. The underlying causes of these diseases have yet to be precisely elucidated, making the research and development of treatments extremely challenging. Cures for these disorders remain elusive, while expectations from patients and their families for new, better drugs remain high.
The creation of ground-breaking medicines often involves many failures - but viewed from a new angle, these can sometimes be seen as spurs to try different research approaches. Such was the case when scientists researching non-drowsy antihistamines found that mice fell asleep during tests of drug candidates. Although not suitable as antihistamines, they speculated that the candidates might have an effect on the central nervous system (CNS). Ultimately research pursued a different path that culminated in the discovery of the antipsychotic ABILIFY. Taking untraveled paths has characterized Otsuka's CNS-related research during the past 40 years.

In 2002, we released the anti-psychotic drug "ABILIFY" in the United States, our first original medication. Many antipsychotic drugs that were sold at that time had antagonist effects that inhibited the dopamine D₂ receptor. However, ABILIFY works by suppressing dopamine neurotransmission when dopamine secretion is excessive, and activating it when there is deficient dopamine secretion, meaning that it has the world's first dopamine system stabilizer (DSS) mechanism.
CNS diseases and their treatments are often accompanied by adherence issues: patients may lack an understanding of their condition, dislike the side effects of their medication and stop taking it, or forget to take it. This often leads to relapses. For better patient outcomes and improved adherence, desirable antipsychotic medications are effective but also have minimal side effects. Due to its unique characteristics, ABILIFY has gained wide recognition and usage from doctors and patients worldwide, and is now used in approximately 60 countries and regions.

Addressing the issue of patient adherence to medication from another direction, Otsuka Pharmaceutical developed the antipsychotic ABILIFY Maintena, a once-monthly injectable suspension. Development of ABILIFY Maintena began before ABILIFY had even gained approval, and production requires sterile production facilities and additional cutting-edge technologies. Lacking these in-house, Otsuka acquired the necessary technology and expertise from scratch. Launched in the U.S. in 2013, and Japan in 2015, the drug is now used in over 50 countries.
The research plan for future antipsychotic drugs as successors to ABILIFY began in 1999. The team, which consisted of members from fields including synthesis, pharmacology and safety, combined their experience and knowledge to work toward next-generation solutions.In 2015, the new antipsychotic REXULTI was approved by the U.S. FDA as adjunctive treatment for adults with major depressive disorder and as a treatment for adults with schizophrenia. This drug, which is believed to exert a partial agonistic effect on the dopamine receptor D₂ and serotonin receptor 5-HT_1A and an antagonistic effect on serotonin receptor 5-HT_2A (Serotonin Dopamine Activity Modulator: SDAM), is now used in approximately 60 countries. We are also pursuing phase III clinical trials for the treatment of agitation in Alzheimer's-type dementia.^*

Looking to help patients with psychiatric diseases and their caregivers or doctor to measure whether the patient is taking their medication, Otsuka and U.S. -based Proteus Digital Health, Inc. have developed a digital medical system that combines Otsuka's ABILIFY with the Proteus ingestible sensor embedded in a single pill to digitally record ingestion. Otsuka obtained FDA approval for Abilify MyCite in the U.S. in 2017.

In addition to creating new products on our own, we collaborate with other companies to share our strengths and ideas in order to discover, develop and deliver high-value, breakthrough products.

Business Collaborators

CNS area

In addition to our antipsychotic drugs REXULTI, ABILIFY Maintena and ABILIFY, we have marketing rights to Neupro patch, a transdermal dopamine agonist used to treat restless legs syndrome and Parkinson's disease. In the U.S. we also market NUEDEXTA^*, the first approved treatment for pseudobulbar affect (PBA, involuntary, sudden, and frequent episodes of laughing and/or crying).

• *Sold in the U.S.

• More information on our work in the CNS area

Otsuka product development stories