Therapeutic Potential of Vortioxetine for Anhedonia-Like Symptoms in Depression: A Post Hoc Analysis of Data from a Clinical Trial Conducted in Japan

Koichiro Watanabe,1 Shinji Fujimoto,2 Tatsuro Marumoto,2 Tadayuki Kitagawa,3 Kazuyuki Ishida,3 Tadashi Nakajima,2 Yoshiya Moriguchi,4 Keita Fujikawa,2 Takeshi Inoue5 1Department of Neuropsychiatry, Kyorin University School of Medicine, Tokyo, Japan; 2Japan Medical Office, Takeda Pharmaceutical Co., Ltd, Tokyo, Japan; 3Takeda Development Center – Japan, Takeda Pharmaceutical Co., Ltd, Osaka, Japan; 4Medical Affairs, Lundbeck Japan K.K., Tokyo, Japan; 5Department of Psychiatry, Tokyo Medical University, Tokyo, JapanCorrespondence: Koichiro Watanabe, Department of Neuropsychiatry, Kyorin University School of Medicine, 6-20-2 Shinkawa, Mitaka, Tokyo, 181-8611, Japan, Tel +81-422-47-5511, Fax +81-422-45-4697, Email koichiro@tke.att.ne.jpAim: Anhedonia in major depressive disorder may be resistant to first-line antidepressants. We examined the effect of vortioxetine, a multimodal antidepressant, on anhedonia-like symptoms in Japanese patients with major depressive disorder.Methods: This was a post hoc analysis of an 8-week, randomized, double-blind, placebo-controlled, phase 3 study of vortioxetine (10 mg or 20 mg) in Japanese patients aged 20– 75 years with recurrent major depressive disorder and a Montgomery–Åsberg Depression Rating Scale (MADRS) total score of at least 26. The primary outcome was the mean change from baseline to week 8 in anhedonia-like symptoms as measured by MADRS anhedonia factor score, composed of: Q1, apparent sadness; Q2, reported sadness; Q6, concentration; Q7, lassitude; and Q8, inability to feel. Mean change in MADRS total score and anhedonia factor score were compared among treatment groups, with data categorized by median baseline anhedonia factor score (0– 17 or ≥ 18).Results: Data were available for 489 patients. The least-squares mean difference in MADRS anhedonia factor score change from baseline to week 8 versus placebo was − 1.34 for vortioxetine 10 mg (P = 0.0300) and − 1.77 for vortioxetine 20 mg (P = 0.0044). The least-squares mean difference between vortioxetine and placebo in MADRS total score change from baseline to week 8 was − 3.11 (10 mg dose) and − 3.37 (20 mg dose) for patients with a higher baseline anhedonia factor score (≥ 18), and − 2.08 (10 mg) and − 2.61 (20 mg) for patients with a lower baseline score (0– 17).Conclusion: This post hoc analysis suggests that vortioxetine may have therapeutic potential in patients with anhedonia-like symptoms of major depressive disorder. ClinicalTrials.gov identifier for primary study: NCT02389816.Keywords: anhedonia, antidepressant, Japanese, major depressive disorder, vortioxetine