vortioxetine and Headache

These post hoc analyses evaluate the efficacy, safety, and tolerability of vortioxetine versus placebo in patients aged ≥55 years with major depressive disorder (MDD).. Study-level efficacy data from 12 short-term, fixed-dose, randomized, placebo-controlled trials of vortioxetine 5-20 mg/day were assessed using a random-effects meta-analysis. Adverse events (AEs), vital signs, ECG values, liver enzymes, and body weight were pooled from the same studies. Patients had baseline Montgomery-Åsberg Depression Rating Scale (MADRS) total scores ranging from 22-30.. 1508 patients (mean age=62.4 years; range, 55-88 years) were included. Mean differences from placebo in change from baseline to study end (6/8 weeks) in MADRS were -2.56 (5 mg, n=324, P=0.035), -2.87 (10 mg, n=222, P=0.007), -1.32 (15 mg, n=90, P=NS), and -4.65 (20 mg, n=165, P=0.012). Odds ratios for response versus placebo were 1.6 (5 mg, P=NS), 1.8 (10 mg, P=0.002), 1.2 (15 mg, P=NS), and 2.5 (20 mg, P<0.001), and for remission versus placebo were 1.5 (5 mg, P=NS), 1.5 (10 mg, P=NS), 1.4 (15 mg, P=NS), and 2.7 (20 mg, P=0.001). The proportion of patients with AEs for placebo and vortioxetine 5-20 mg was 61.5% and 62.3%, respectively, with no increase at increased doses. Vortioxetine demonstrated a placebo-level incidence of serious AEs (1.2%). AEs occurring in ≥5% of any treatment group were nausea, headache, diarrhea, dizziness, dry mouth, constipation, fatigue, vomiting, and anxiety. No clinically significant mean changes in vital signs, ECG values, liver enzymes, or body weight emerged during treatment.. Vortioxetine 5-20 mg/day is efficacious and well tolerated in MDD patients aged ≥55 years, a group that is often comorbid with other conditions and treated with other medications.

Topics: Aged; Aged, 80 and over; Antidepressive Agents; Anxiety; Constipation; Depressive Disorder, Major; Diarrhea; Dizziness; Fatigue; Headache; Humans; Middle Aged; Nausea; Odds Ratio; Piperazines; Randomized Controlled Trials as Topic; Selective Serotonin Reuptake Inhibitors; Sulfides; Treatment Outcome; Vomiting; Vortioxetine; Xerostomia

Coexisting anxiety is common in major depressive disorder (MDD) and more difficult to treat than depression without anxiety. This analysis assessed the efficacy, safety, and tolerability of vortioxetine in MDD patients with high levels of anxiety (baseline Hamilton Anxiety Rating Scale [HAM-A] total score ≥20).. Efficacy was assessed using an aggregated, study-level meta-analysis of 10 randomized, placebo-controlled, 6/8-week trials of vortioxetine 5-20mg/day in adults (18-75 years), with a study in elderly patients (≥65 years) analyzed separately. Outcome measures included mean differences from placebo in change from baseline to endpoint (Δ) in the Montgomery-Åsberg Depression Rating Scale (MADRS), HAM-A total, and HAM-A subscales. Safety and tolerability were assessed by treatment-emergent adverse events (TEAEs).. A total of 1497 (48.6%) vortioxetine-treated and 860 (49.1%) placebo-treated patients had baseline HAM-A≥20. There were significant differences from placebo in MADRS (vortioxetine 5mg/day, n=415, Δ-2.68, P=0.005; 10mg/day, n=373, Δ-3.59, P<0.001; 20mg/day, n=207, Δ-4.30, P=0.005) and HAM-A total (5mg/day, n=419, Δ-1.64, P=0.022; 10mg/day, n=373, Δ-2.04, P=0.003; 20mg/day, n=207, Δ-2.19, P=0.027). There were significantly greater improvements versus placebo on the HAM-A psychic subscale for all doses. The most common TEAEs (≥5.0%) were nausea, headache, dizziness, dry mouth, diarrhea, nasopharyngitis, constipation, and vomiting. Incidence of serious TEAEs was 1.3% (placebo) and ≤1.3% (vortioxetine, across doses).. Study heterogeneity limits this analysis. Patients with baseline HAM-A≥20 were not directly compared to baseline HAM-A<20 or total MDD population.. Vortioxetine was efficacious in reducing depressive and anxiety symptoms in patients with MDD and high levels of anxiety.

Topics: Anxiety; Depressive Disorder, Major; Diarrhea; Dizziness; Double-Blind Method; Headache; Humans; Nasopharyngitis; Nausea; Piperazines; Selective Serotonin Reuptake Inhibitors; Sulfides; Treatment Outcome; Vomiting; Vortioxetine; Xerostomia

This meta-analysis assessed the efficacy and safety of 5 mg/day vortioxetine compared to placebo for adult major depressive disorder.. We performed a meta-analysis of the double-blind, randomized, controlled clinical trials involving 5 mg/day vortioxetine in adult patients with major depressive disorder published on PubMed, EBSCO, and PsycINFO, and the Clinical Trials databases were searched from 2000 through October 2013. The abstracts for the Annual Meetings of the American Psychiatric Association (APA) and previous reviews were searched to identify additional studies. Results were expressed with odds ratios (ORs) with their 95 % confidence interval (CI). The effect size (ES) for the four studies was derived by computing the standardized mean difference (SMD). The data were pooled with a random effects model.. Five RCTs met the selection criteria. Results of the meta-analysis showed the following: (1) The treatment response of 5 mg/day vortioxetine group was greater than placebo group (OR=1.84, 95 % CI=1.16-2.93, Z=2.59, P=0.010), and there was a significant antidepressant effect of vortioxetine (ES=2.98, P=0.001). However, there was no significant difference in remission (OR=1.47, 95 % CI=0.95-2.30, Z=1.71, P=0.090). (2) The common adverse effects included nausea, dizziness, headache, dry mouth, and diarrhea. There was a significant difference for nausea between the two groups (OR=3.01, 95 % CI=2.22-4.09, Z=7.08, P=0.00001), but no significant differences were observed for the other four adverse effects.. For the treatment of major depressive disorder, our results show that a dose of 5 mg/day vortioxetine was more effective, but more easily induced nausea, compared to placebo.

Topics: Antidepressive Agents; Depressive Disorder, Major; Headache; Humans; Nausea; Piperazines; Placebo Effect; Randomized Controlled Trials as Topic; Sulfides; Treatment Outcome; Vortioxetine

This study assessed the efficacy, tolerability and safety of vortioxetine versus placebo in adults with recurrent major depressive disorder. This double-blind, randomized, placebo-controlled study included 608 patients [Montgomery-Åsberg Depression Rating Scale (MADRS) total score ≥ 26 and Clinical Global Impression - Severity score ≥ 4]. Patients were randomly assigned (1 : 1 : 1 : 1) to vortioxetine 15 mg/day, vortioxetine 20 mg/day, duloxetine 60 mg/day or placebo. The primary efficacy endpoint was change from baseline in MADRS total score at week 8 (mixed model for repeated measurements). Key secondary endpoints were: MADRS responders; Clinical Global Impression - Improvement scale score; MADRS total score in patients with baseline Hamilton Anxiety Rating Scale ≥ 20; remission (MADRS ≤ 10); and Sheehan Disability Scale total score at week 8. On the primary efficacy endpoint, both vortioxetine doses were statistically significantly superior to placebo, with a mean difference to placebo (n = 158) of -5.5 (vortioxetine 15 mg, P < 0.0001, n = 149) and -7.1 MADRS points (vortioxetine 20 mg, P < 0.0001, n = 151). Duloxetine (n = 146) separated from placebo, thus validating the study. In all key secondary analyses, both vortioxetine doses were statistically significantly superior to placebo. Vortioxetine treatment was well tolerated; common adverse events (incidence ≥ 5%) were nausea, headache, diarrhea, dry mouth and dizziness. No clinically relevant changes were seen in clinical safety laboratory values, weight, ECG or vital signs parameters. Vortioxetine was efficacious and well tolerated in the treatment of patients with major depressive disorder.

Topics: Adolescent; Adult; Aged; Depressive Disorder, Major; Double-Blind Method; Duloxetine Hydrochloride; Female; Headache; Humans; Internationality; Male; Middle Aged; Nausea; Piperazines; Psychiatric Status Rating Scales; Selective Serotonin Reuptake Inhibitors; Sulfides; Thiophenes; Treatment Outcome; Vortioxetine; Young Adult

The primary objective of this study was to evaluate the safety and tolerability of the investigational drug vortioxetine (Lu AA21004) in the long-term treatment of patients with major depressive disorder.. Patients entered this 52-week, open-label extension study after completing an 8-week lead-in study. Safety and tolerability were evaluated at regular intervals on the basis of spontaneously reported adverse events (AEs), clinical safety laboratory tests, vital signs, ECG and physical examination. Effectiveness of treatment was assessed using the Montgomery-Åsberg Depression Rating Scale (MADRS) total score.. A total of 535 patients were treated and 61.3% (n = 328) completed the study, resulting in 393 patient years of exposure to vortioxetine. AEs reported by ≥10% of patients were nausea, headache, and nasopharyngitis. Taken together, six patients had eight AEs related to sexual dysfunction. There were no clinically significant safety findings with respect to mean changes of vital signs, weight, ECG parameters, or clinical laboratory values. Patients entered the extension study with a mean MADRS total score of 13.5 ± 8.7. The mean MADRS total score decreased (improved) by approximately 8 points to 5.5 ± 6.0 at Week 52 (OC). By the end of the study, the proportion of responders had increased from 63% to 94% (OC), as had the proportion in remission (MADRS ≤10), increasing from 42% to 83% (OC). Patients in remission (n = 226) at the start of this study had a relapse rate (MADRS ≥22) of 9.7%.. As with all open-label studies, the conclusions that can be drawn are limited by the lack of a placebo control, making it difficult to assess causality of any changes in outcome measures. However, on the basis of these findings, vortioxetine (2.5, 5, 10 mg/day) demonstrated a favourable safety and tolerability profile and maintained effectiveness over 12 months of treatment.. This study has the ClinicalTrials.gov identifier: NCT00694304.

Topics: Adolescent; Adult; Aged; Depressive Disorder, Major; Electrocardiography; Female; Headache; Humans; Longitudinal Studies; Male; Middle Aged; Nasopharyngitis; Nausea; Piperazines; Sexual Dysfunction, Physiological; Sulfides; Vortioxetine