[A history of investigation on the mood-stabilizing effect of carbamazepine in Japan].

The initial open trials on the antimanic and prophylactic effects of carbamazepine (CBZ) were performed in Japan in the early 1970s (Takezaki H, Hanaoka M, 1970; Okuma T et al. 1973) and the mood-stabilizing effects of CBZ was reported for the first time in the world. We confirmed the antimanic effect by a multi-institutional double-blind group comparison study with chlorpromazine as the control drug in the last 1970s. Prophylactic effect was confirmed by a double-blind study using inactive placebo as the control in 1981. Following the initial studies in Japan, many reports supporting the antimanic and prophylactic effects of CBZ and valproate began to appear in the world and the category of "mood-stabilizers" including lithium and antiepileptic drugs was established. The responses to CBZ and lithium were not always parallel each other and it was suggested that the mechanism of mood-stabilizing effect of CBZ and lithium may be different. It was also shown that patients who had not responded favorably to both of CBZ and lithium sometimes responded favorably to the combination of CBZ and lithium. During the course of our double-blind trials, the problem of different therapeutic dosages of psychotropic drugs between Japan and Western countries, i.e. lower dosage in Japan, emerged and caused the delay of publication of our results in Western journals.