Psychiatric Drug Development in Japan

Abstract

A wide variety of drugs prescribed by psychiatrists in Western countries are not yet available in Japan. The manufacturers of these drugs are often reluctant to conduct the expensive clinical trials required by the Japanese government for their approval; they have already incurred such expenses in other countries, and the market for psychiatric drugs in Japan can be uncertain. Moreover, the Japanese clinical trial system has many methodological problems, which the government has only now started to address. An international agreement to make the results of drug trials reciprocal among participating countries would reduce costs for governments as well as drug manufacturers.

Delays in psychiatric drug development in Japan

“…Execution of phase III protocols is the most problematic process for CNS drugs 13 . Flaws in the methodology of clinical trials in Japan in the 1990s 1,14 and difficulty in demonstrating efficacy of antidepressants 15 resulted in unavailability of five globally used antidepressants, namely, bupropion, citalopram, escitalopram, fluoxetine and venlafaxine.…”

“…This indicates that the 20‐year delay was because of a delay in the development of the drug rather than in the review of the application. Circumstances exclusive to Japan may have affected the development of clozapine 1 . In 1975, the application for the approval of clozapine to Japan’s Ministry of Health, Labor and Welfare (MHLW) was retracted as in other countries because of a concern about agranulocytosis.…”

“…These incidents deeply affected both regulators and pharmaceutical companies regarding drug safety, and they became extremely cautious while developing and approving new drugs, particularly those with a dubious risk–benefit balance such as clozapine. Another trial involving clozapine in Japan began in 1995, but suffered methodological flaws 1 . Moreover, MHLW required duplication of phase II and III data to confirm efficacy and safety for Japanese subjects, as the ICH E5 guideline was not yet implemented.…”

“…Circumstances exclusive to Japan may have affected the development of clozapine. 1 In 1975, the application for the approval of clozapine to Japan's Ministry of Health, Labor and Welfare (MHLW) was retracted as in other countries because of a concern about agranulocytosis. In 1989, when clozapine was approved in the USA, HIV-infected haemophiliacs in Japan filed lawsuits demanding compensation from MHLW and five pharmaceutical companies.…”

“…Until 1996, 1 none of the newer psychiatric drugs, approved in the previous decade and commonly used in the West, were available in Japan. Japanese psychiatrists had to treat their patients only with classical antipsychotics, tricyclic antidepressants and benzodiazepines.…”