Antidepressants in Japan

While the market has seen the entry of the selective serotonin reuptake inhibitors (SSRIs) fluvoxamine (Luvox-Fujisawa, Depromel-Meiji Seika), paroxetine (Paxil-GSK), sertraline (Zoloft-Pfizer), and the SNRI milnacipran (Toledomin-Asahi Kasei-Janssen), other antidepressants including citalopram (Cipramil/Cipralex-Lundbeck), fluoxetine (Prozac-Eli Lilly) and others are either still under investigation in Japan or have dropped their pursuit on gaining entry into the Japanese market.[3]

Although none of the antidepressants on the market in Japan have been studied using placebo controls, this had begun to change since the beginning of the 2000s. Prior clinical developments have pitted the new drug against a drug already on the market using a non-inferiority method of comparison, however, this method is known to be subject to placebo effects, e.g. depressive symptoms lifting due to effects other than pharmacologic drug effect.[2]

According to a Japanese medical report in 2002, Trazodone and tricyclic antidepressants (TCAs) were widely available in Japan while only two SSRIs (paroxetine and fluvoxamine) were marketed.[4] A third SSRI, sertraline, received approval in April 2006 after over 15 years of clinical trial development in Japan.[5][6]

Fluvoxamine was the first SSRI to be approved in Japan in 1999 [7][8] The three most sold antidepressants by the end of 2010 were paroxetine with a value market share of 37%, sertraline with a share of 20% and fluvoxamine with a share of 15%.[9]

The Japan algorithm for mood disorders[10] does not include many of the post-tricyclic antidepressants used as first-line antidepressants in Western countries for almost two decades, and recent studies are still comparing SSRIs and tricyclic antidepressants, even though tricyclics are clearly 2nd or 3rd line treatments in the West.[11] Organon International and Meiji Seika have filed an application for approval of mirtazapine in Japan, a drug on the market in many Western countries since 1994.[12] Meiji Seika is commercializing mirtrazapine(brand name Reflex)[13][14] in Japan which was approved for depression in 2009.[15]

SNRI Duloxetine (Cymbalta - Shionogi and Eli Lilly Japan) was first approved in Japan in 2010 for major depressive disorder.[16][17] In the following years it gained approval for diabetic neuropathy pain, fibromyalgia, chronic low back pain and osteoarthritis.[18][19][20][21]

Citalopram (Lundbeck), an SSRI on the market since the late 1980s is not available in Japan, however on April 22, 2011 escitalopram (the S-isomer enantiomer of citalopram), was approved for use.[22] There is little news, however, on the status of bupropion (Glaxo Smith-Kline), used widely in Western countries since the early 1990s and long in clinical trials in Japan.

More current data shows the three most sold antidepressants in Japan in 2017 were duloxetine, mirtazapine, and escitalopram (Lexapro).[23]

Takeda and Lundbeck submitted vortioxetine (Trintellix) to the Ministry of Health, Labour and Welfare in Japan. If approved it may be commercialized in 2019.[24][25]

• Japan Ministry of Health, Labor, and Welfare
• Japan National Center of Neurology and Psychiatry
• Tokyo Institute of Psychiatry (merged)
• Japan Pharmaceutical Consultants

• Higuchi, Briley, 2007. Japanese experience with milnacipran, the first serotonin and norepinephrine reuptake inhibitor in Japan