Acceptability of escitalopram versus duloxetine in outpatients with depression who did not respond to initial second-generation antidepressants: A randomized, parallel-group, non-inferiority trial.

BACKGROUNDS: Antidepressants are widely used to treat major depressive disorder. First-line treatments with antidepressants are only successful in one-third of patients; however, evidence from randomized controlled trials on second-line treatments is limited. Moreover, recently acceptability is suggested to be a good indicator of overall treatment success. METHODS: This is a multi-center two-arm, three-phased randomized controlled trial performed in Japan from December 2013 to March 2017 comparing the acceptability of escitalopram and duloxetine as a second-line drug. Patients, who failed to respond to antidepressants such as sertraline, paroxetine, fluvoxamine, milnacipran or mirtazapine for at least 3 weeks, were randomized to either escitalopram (Group A) or duloxetine (Group B) in Step 1 (8 weeks). In Step 2 (8 weeks), the drug was switched to the other if the first drug failed. The discontinuation rate at the end of Step 1 was the primary endpoint and non-inferiority of escitalopram vs duloxetine was tested. In addition, change in clinical measures from baseline were also assessed at the end of Step 1, 2 and up to 52 weeks. RESULTS: At the end of Step 1, Group A (n = 82) was significantly superior to Group B (n = 78) in discontinuation rate (4.9% to 19.2%, P = 0.007). The change in clinical indices from baseline were not different between the groups at either timepoint. LIMITATIONS: As the major reason for discontinuation in Group B was the "withdrawal of consent" the concrete reason could not be verified. CONCLUSIONS: As a second-line treatment drug, escitalopram was suggested to be non-inferior to duloxetine in acceptability. TRIAL REGISTRATION: UMINCTR(UMIN000012367), registered on December 1st, 2013 and last updated on April 4th, 2017.

Prediction and structural equation model of sertraline treatment response in Japanese patients with major depressive disorder.

OBJECTIVE: The aim of this study was to extract the factors possibly associated with sertraline treatment response and elucidate their interactions and extent of influence. METHODS: Demographic state, stress state, personality, and eight genetic polymorphisms at baseline and clinical symptoms at baseline and 8 weeks were analyzed and examined by logistic regression and a structural equation model in sertraline treatment study of 96 Japanese patients with major depressive disorder. RESULTS: Non-responders were associated with higher scores of harm avoidance in Temperament and Character Inventory, higher scores (≥24) of 17-item Hamilton Rating Scale for Depression at baseline, recurrence, and 12/12 genotype of the serotonin transporter variable number of tandem repeat polymorphism in intron 2 (5HTTSTin2). When we calculated the response index using four factors extracted, the mean response index value of non-responders was significantly higher than that of responders. The symptoms at baseline, personality, recurrence, and polymorphism of 5HTTSTin2 showed significantly direct and positive influences on the symptoms at 8 weeks in our final structural equation model with a good model fit. CONCLUSION: Considering the combination of four factors extracted may be useful for predicting a worse response to sertraline treatment and selecting different treatment other than sertraline.

Repetitive transcranial magnetic stimulation induces kf-1 expression in the rat brain.

Repetitive transcranial magnetic stimulation (rTMS) is a non-invasive approach used for stimulating the brain, and has proven effective in the treatment of depression, however the mechanism of its antidepressant action is unknown. Recently, we have reported the induction of kf-1 in rat frontal cortex and hippocampus after chronic antidepressant treatment and repeated electroconvulsive treatment (ECT). In this study, we demonstrated the induction of kf-1 after rTMS in the rat frontal cortex and hippocampus, but not in hypothalamus. Our data suggest that kf-1 may be a common functional molecule that is increased after antidepressant treatment, ECT and rTMS. In conclusion, it is proposed that induction of kf-1 may be associated with the treatment induced adaptive neural plasticity in the brain, which is a long-term target for their antidepressant action.