[Mechanism of action of new generation antidepressants under development in Japan: focusing on dopamine neurotransmission]

In the medication of depression, the antidepressants such as selective 5-HT reuptake inhibitors (SSRIs) and a 5-HT and NA reuptake inhibitor (SNRI) are mainly in use in Japan. However, remission rates for SSRI or SNRI are 60% or less. This means that there are still many patients with treatment-resistant depression (TRD). Meanwhile it is considered that the DA nerve system plays an important role for recovery from troublesome feelings and a sense of aimlessness in life in patients with TRD. Recently, new generation antidepressants under development in Japan (escitalopram, duloxetine, mirtazapine, and bupropion) are expected as an option in the medical treatment of TRD. We introduce the pharmacological (focusing on the DA nerve system) and clinical data on these new antidepressants and their putative positioning of each antidepressant. Escitalopram is a stronger and safer SSRI with an earlier onset of action. The antidepressant effect of duloxetine is considered stronger than that of other SNRIs. Mirtazapine is an antagonist of alpha2, 5-HT2A, and 5-HT2C receptors and promotes releases of NA, 5-HT, and DA. Clinically, mirtazapine shows an earlier onset of action and a sedative effect. Bupropion is a DA and NA reuptake inhibitor, and is considered useful to activate DA neurons.