Efficacy and tolerability of vortioxetine versus agomelatine, categorized by previous treatment, in patients with major depressive disorder switched after an inadequate response.

This study aimed to evaluate if efficacy and tolerability of switching to vortioxetine is independent of previous SSRI or SNRI treatment in patients who had been inadequately treated for their current major depressive episode. Patients from a double-blind, 12-week comparator study were randomized (1:1) to vortioxetine (10-20 mg/day) or agomelatine (25-50 mg/day). The pre-defined primary efficacy endpoint was change from baseline to week 8 in MADRS total score analyzed by MMRM. An ANCOVA-LOCF was conducted as a sensitivity analysis. These analyses were repeated in subgroups according to previous antidepressant treatment. In the overall population, vortioxetine (n = 252) was significantly superior to agomelatine (n = 241) by -2.2 MADRS points (p < 0.01) at week 8. ∼77% (n = 189/vortioxetine, n = 188/agomelatine) were previously treated with an SSRI (citalopram, escitalopram, paroxetine, sertraline) and ∼23% (n = 62/vortioxetine, n = 52/agomelatine) with an SNRI (duloxetine, venlafaxine). Baseline characteristics were similar in all subgroups. Treatment differences (MMRM) in MADRS total score were -2.6 and -2.3 (n = 164/vortioxetine, n = 150/agomelatine) (p < 0.01) for patients switching from an SSRI and -1.8 and -1.5 (n = 56/vortioxetine, n = 40/agomelatine) (p > 0.05) from an SNRI at weeks 8 and 12, respectively; non-significant improvements were seen for each of the 6 previous antidepressants. Improvements in HAM-A, CGI-I, and EQ-5D scales were significant for the SSRI subgroup and non-significant for the SNRI subgroup. Withdrawal and adverse event rates were similar, regardless of previous SSRI or SNRI treatment. These subgroup analyses showed statistical superiority of vortioxetine to agomelatine in inadequate responders to SSRIs and statistically non-significant improvements in the smaller SNRI subgroup, while being equally well tolerated. TRIAL REGISTRATION: This study has the ClinicalTrials.gov identifier NCT01488071.

Efficacy of Vortioxetine on Cognitive Functioning in Working Patients With Major Depressive Disorder.

OBJECTIVE: This post hoc analysis investigates the effect of vortioxetine on cognitive functioning and depressive symptoms in working adults with major depressive disorder (MDD). METHODS: Population data from FOCUS, a double-blind, randomized, placebo-controlled study investigating the efficacy of vortioxetine versus placebo on cognitive functioning and depression in patients with MDD, were used to analyze mean change from baseline scores for the Digit Symbol Substitution Test (DSST), Trail Making Test A/B (TMT-A/B), Stroop, and Perceived Deficits Questionnaire (PDQ). FOCUS, conducted from December 2011 through May 2013, included adult patients with recurrent MDD according to DSM-IV-TR criteria. Change in depression severity (Montgomery-Asberg Depression Rating Scale [MADRS] total score) was analyzed using data from 3 additional short-term placebo-controlled studies (2 of which included duloxetine) and 1 relapse prevention study. Analyses were done according to patients' working status at baseline and workplace position. All analyses were made versus placebo. RESULTS: In FOCUS, the effect versus placebo on the DSST was 5.6 for 10 mg and 5.0 for 20 mg (P < .001 for both doses) in working patients; the effect was 4.0 (P < .001 for both doses) in total study population. The effect remained significant when adjusting for change in MADRS. In patients with "professional" positions, the effect was 9.2 for 10 mg (P = .006) and 9.0 for 20 mg (P = .001). A similar pattern of results was also observed for TMT-A/B, Stroop, PDQ, and MADRS total score. The efficacy of duloxetine was not different in working patients (MADRS). CONCLUSIONS: The beneficial effects of vortioxetine on objective and subjective measures of cognitive functioning are greater in working patients with MDD; the observed benefits were independent of improvement in depressive symptoms. TRIAL REGISTRATION: This study is a secondary analysis of data from 5 registered trials: ClinicalTrials.gov identifiers: NCT01422213, NCT00635219, NCT00735709, NCT01140906, NCT00596817​.

Combining escitalopram with gaboxadol provides no additional benefit in the treatment of patients with severe major depressive disorder.

The aim of this proof-of-concept study was to compare the efficacy of escitalopram (20 mg/d) in combination with fixed doses of gaboxadol to escitalopram (20 mg) in the treatment of patients with severe major depressive disorder (MDD). Adult patients were randomized to 8 wk of double-blind treatment with fixed doses of placebo (n=71), escitalopram (20 mg, n=140), escitalopram (20 mg)+gaboxadol (5 mg) (n=139), or escitalopram (20 mg)+gaboxadol (10 mg) (n=140). The pre-defined primary analysis of efficacy was an analysis of covariance (ANCOVA) of change from baseline to endpoint (week 8) in Montgomery-Åsberg Depression Rating Scale (MADRS) total score using last observation carried forward (LOCF). There was no statistically significant difference in the mean change from baseline in MADRS total score between the 20 mg escitalopram+10 mg gaboxadol group and the 20 mg escitalopram group [difference=-0.45 MADRS points (95% CI -2.5 to 1.6, p=0.6619, full analysis set (FAS), LOCF, ANCOVA)] at week 8. The mean treatment differences to placebo at week 8 were -5.6 (95% CI -8.0 to -3.1, p<0.0001) (20 mg escitalopram), -5.1 (95% CI -7.5 to -2.7, p<0.0001) (20 mg escitalopram+5 mg gaboxadol), and -6.0 (95% CI -8.4 to -3.6, p<0.0001) (20 mg escitalopram+10 mg gaboxadol). The most common adverse events reported in the active treatment groups for which the incidence was higher than that in the placebo group, comprised nausea, anxiety and insomnia. There were no clinically relevant efficacy differences between a combination of escitalopram and gaboxadol compared to escitalopram alone in the treatment of severe MDD. All active treatment groups were superior in efficacy to placebo and were well tolerated.

Escitalopram in obsessive-compulsive disorder: a randomized, placebo-controlled, paroxetine-referenced, fixed-dose, 24-week study.

OBJECTIVE: A randomized, placebo controlled fixed-dose trial was undertaken to determine the efficacy and tolerability of escitalopram in obsessive-compulsive disorder (OCD), using paroxetine as the active reference. RESEARCH DESIGN AND METHODS: A total of 466 adults with OCD from specialized clinical centres, psychiatric hospital departments, psychiatric practices, or general practice were randomized to one of four treatment groups: escitalopram 10 mg/day (n = 116), escitalopram 20 mg/day (n = 116), paroxetine 40 mg/day (n = 119), or placebo (n = 115) for 24 weeks. The primary efficacy endpoint was the mean change in the Yale-Brown Obsessive-Compulsive Scale (Y-BOCS) total score from baseline to week 12. Secondary efficacy endpoints included remission (defined as Y-BOCS total score < or =10), NIMH-OCS, and CGI-S and CGI-I scores at weeks 12 and 24. Tolerability was based on the incidence of adverse events, and on changes in vital signs (blood pressure and pulse). Main outcome measures; RESULTS: Escitalopram 20 mg/day was superior to placebo on the primary and all secondary outcome endpoints, including remission. Escitalopram 10 mg/day and paroxetine 40 mg/day were also effective on the primary scale as well as some other outcome measures. In the escitalopram 20 mg/day group, the improvement in Y-BOCS total score was significantly better than in the placebo group as early as week 6. The most common AEs in the active treatment groups were nausea (19-27%), headache (17-22%), and fatigue (12-19%). More paroxetine-treated patients withdrew due to adverse events than escitalopram- or placebo-treated patients. CONCLUSION: Given that escitalopram 20 mg/day was associated with an earlier onset, higher response and remission rates, improved functioning, and better tolerability than the reference drug, escitalopram deserves to be considered as one of the first-line agents in the pharmacotherapy of OCD for longer-term treatment periods.

Escitalopram prevents relapse of obsessive-compulsive disorder.

To examine the efficacy and tolerability of escitalopram in the prevention of relapse in patients with OCD, 468 patients with OCD were treated with open label escitalopram (10 mg or 20 mg) for 16 weeks, after which the 320 responders (Y-BOCS total score decrease > or =25%) were randomised to placebo or escitalopram (at the assigned dose) for 24 weeks double-blind treatment. The primary analysis (time to relapse) showed a significant advantage for escitalopram (p<0.001, log-rank test). The proportion of patients who relapsed was statistically significantly higher in the placebo group (52%) than in the escitalopram group (23%) (p<0.001, chi(2)-test). The risk of relapse was 2.74 times higher for placebo compared to escitalopram. Escitalopram was well tolerated and improvements in obsessive-compulsive symptoms reported during the open label period were sustained during the double-blind extension of treatment with active drug. These results demonstrate that escitalopram is effective for long-term treatment and relapse prevention in OCD.

A prospective study of escitalopram in the treatment of major depressive episodes in the presence or absence of anxiety.

This open, multicenter, prospective study in France assessed the efficacy and tolerability of escitalopram in patients with depression, with or without comorbid anxiety. Escitalopram was administered over a 12-week treatment period to 790 depressed patients, including 482 patients with at least one concomitant anxiety disorder. The study was completed by 649 patients. At baseline, the mean Montgomery-Asberg Depression Rating Scale (MADRS) total score was 31.5 and decreased to 12.4 at end point (last observation carried forward [LOCF]). The MADRS score decreased by 20.5 points in patients with no anxiety disorder and by 18.3 points in patients with at least one concomitant anxiety disorder. The mean Hamilton Anxiety Rating Scale (HAM-A) total score at baseline was 25.6, which decreased to 10.8 at end point (LOCF). The HAM-A score decreased by 13.8 points in patients with no anxiety disorder and by 15.5 points in patients with at least one anxiety disorder. Adverse events were reported by 246 patients (31%). The most frequent adverse events were nausea in 65 patients (8%) and headache in 38 patients (5%); 61 patients (8%) discontinued treatment due to adverse events. Escitalopram was well tolerated and efficacious in reducing symptoms of depression in patients with or without comorbid anxiety over a 12-week treatment period.

Safety and efficacy of oral escitalopram as continuation treatment of intravenous citalopram in patients with major depressive disorder.

The objective of this open-label, multicentre study was to evaluate the safety and efficacy of treatment with escitalopram (10 or 20 mg/day) for 6 weeks following a switch from intravenous citalopram treatment (20 or 40 mg/day) in patients presenting with a major depressive episode. A total of 173 patients were included, 147 (85%) of whom completed the study. The mean Montgomery-Asberg Depression Rating Scale (MADRS) total score at inclusion (last citalopram dose) was 31.6 +/- 9.9. The MADRS score decreased to 23.4 +/- 10.5 after 3 days of oral treatment with escitalopram and was 12.7 +/- 9.3 at the end of the study. The scores on the Clinical Global Impression (CGI) and Patient Global Evaluation scales also improved: at the end of the study, the response rates were 67% on the MADRS (defined as >or=50% decrease from MADRS baseline score) and 68% on the CGI-I (defined as CGI-I