Vortioxetine in patients with major depressive disorder and high levels of anxiety symptoms: An updated analysis of efficacy and tolerability

Background: Patients with major depressive disorder (MDD) often experience comorbid anxiety symptoms. Vortioxetine has demonstrated efficacy in treating anxiety symptoms in patients with MDD; however, efficacy and tolerability have not been assessed across the entire approved dosage range. Methods: The efficacy and tolerability of vortioxetine 5-20 mg/day were assessed in patients with MDD and high levels of anxiety symptoms (Hamilton Anxiety Rating Scale [HAM-A] total score ≥ 20) using pooled data from four randomized, fixed-dose, placebo-controlled studies (n = 842). Data from a randomized, double-blind study of vortioxetine 10-20 mg/day versus agomelatine 25-50 mg/day in patients with an inadequate response to prior therapy (n = 299) were analyzed separately. Mean changes from baseline in Montgomery-Åsberg Depression Rating Scale (MADRS), HAM-A, and Sheehan Disability Scale (SDS) total scores were analyzed by vortioxetine dosage. Results: The pooled analysis of fixed-dose studies demonstrated a clear dose-response relationship for vortioxetine 5-20 mg/day for improvements in MADRS, HAM-A, and SDS total scores. Vortioxetine 20 mg/day demonstrated significant effects versus placebo from week 4 onwards. In the post hoc analysis of the active-controlled study in patients with inadequate response to prior therapy, vortioxetine 10-20 mg/day was superior to agomelatine across all outcome measures from week 4 onwards. Up-titration of vortioxetine to 20 mg/day was not associated with an increase in adverse events. Limitations: Short-term trials. Conclusions: Vortioxetine is efficacious and well tolerated in patients with MDD and high levels of anxiety symptoms, including those with an inadequate response to prior therapy. The greatest therapeutic benefits were observed with vortioxetine 20 mg/day. Trial registration: NCT01140906, NCT01153009, NCT01163266, NCT01255787, NCT01488071

Clinical benefits of vortioxetine 20 mg/day in patients with major depressive disorder

Background: Vortioxetine has demonstrated dose-dependent efficacy in patients with major depressive disorder (MDD), with the greatest effect observed with vortioxetine 20 mg/day. This analysis further explored the clinical relevance of the more rapid and greater improvement in depressive symptoms observed with vortioxetine 20 mg/day vs 10 mg/day. Methods: Analysis of pooled data from six short-term (8-week), randomized, placebo-controlled, fixed-dose studies of vortioxetine 20 mg/day in patients with MDD (N = 2620). Symptomatic response (≥50% decrease in Montgomery-Åsberg Depression Rating Scale [MADRS] total score), sustained symptomatic response, and remission (MADRS total score ≤10) were assessed by vortioxetine dosage (20 or 10 mg/day). Results: After 8 weeks, 51.4% of patients receiving vortioxetine 20 mg/day had achieved symptomatic response vs 46.0% of those receiving vortioxetine 10 mg/day (P < .05). Significantly more patients achieved symptomatic response vs placebo from week 2 onwards for vortioxetine 20 mg/day and from week 6 onwards for vortioxetine 10 mg/day (both P ≤ .05). Sustained response was achieved from week 4 for 26.0% of patients receiving vortioxetine 20 mg/day vs 19.1% of those receiving vortioxetine 10 mg/day (P < .01), increasing to 36.0% and 29.8%, respectively, over the 8-week treatment period (P < .05). At week 8, 32.0% of patients receiving vortioxetine 20 mg/day were in remission vs 28.2% of those receiving vortioxetine 10 mg/day (P = .09). Rates of adverse events and treatment withdrawal were not increased during the week following vortioxetine dose up-titration to 20 mg/day. Conclusion: Vortioxetine 20 mg/day provides more rapid and more sustained symptomatic response than vortioxetine 10 mg/day in patients with MDD, without compromising tolerability

A double-blind, randomized, placebo-controlled, active reference study of Lu AA21004 in patients with major depressive disorder

The efficacy, safety, and tolerability of Lu AA21004 vs. placebo using venlafaxine XR as active reference in patients with DSM-IV-TR major depressive disorder (MDD) were evaluated. Lu AA21004 is a novel antidepressant that is a 5-HT3 and 5-HT7 receptor antagonist, 5-HT1A receptor agonist, 5-HT1B receptor partial agonist and inhibitor of the 5-HT transporter in recombinant cell lines. In this 6-wk, multi-site study, 429 patients were randomly assigned (1:1:1:1) to 5 or 10 mg Lu AA21004, placebo or 225 mg venlafaxine XR. All patients had a baseline Montgomery–Åsberg Depression Rating Scale (MADRS) total score ⩾30. The primary efficacy analysis was based on the MADRS total score adjusting for multiplicity using a hierarchical testing procedure starting with the highest dose vs. placebo. Lu AA21004 was statistically significantly superior to placebo (n=105) in mean change from baseline in MADRS total score at week 6 (p<0.0001, last observation carried forward), with a mean treatment difference vs. placebo of 5.9 (5 mg, n=108), and 5.7 (10 mg, n=100) points. Venlafaxine XR (n=112) was also significantly superior to placebo at week 6 (p<0.0001). In total, 30 patients withdrew due to adverse events (AEs) – placebo: four (4%); 5 mg Lu AA21004: three (3%); 10 mg Lu AA21004: seven (7%); and venlafaxine: 16 (14%). The most common AEs were nausea, headache, hyperhidrosis, and dry mouth. No clinically relevant changes over time were seen in the clinical laboratory results, vital signs, weight, or ECG parameters. In this study, treatment with 5 mg and 10 mg Lu AA21004 for 6 wk was efficacious and well tolerated in patients with MDD

Factors associated with failure to achieve remission and with relapse after remission in patients with major depressive disorder in the PERFORM study

The Prospective Epidemiological Research on Functioning Outcomes Related to Major Depressive Disorder (PERFORM) study has been initiated to better understand the course of a depressive episode and its impact on patient functioning. This analysis aimed to identify sociodemographic and clinical factors associated with failure to achieve remission at month 2 after initiating or switching antidepressant monotherapy and with subsequent relapse at month 6 for patients in remission at month 2

Epidemiology of Hyperhidrosis in Danish Blood Donors

The risk factors and disease implications of hyperhidrosis are unknown. The objectives of this retrospective cohort study were to estimate the prevalence of hyperhidrosis and to compare demographic, lifestyle, and socioeconomic parameters in blood donors with and without self-reported or hospital-diagnosed hyperhidrosis. The study included blood donors from the Danish Blood Donor Study for the period 2010–2019. Registry data were collected from Statistics Denmark. Overall, 2,794 of 30,808 blood donors (9.07%; 95% confidence interval (95% CI) 8.75–9.40) had self-reported hyperhidrosis and 284 of 122,225 (0.23%; 95% CI 0.21–0.26) had hospital-diagnosed hyperhidrosis. Self-reported hyperhidrosis was associated with smoking (odds ratio (OR) 1.17; 95% CI 1.05– 1.31), overweight (OR 1.72; 95% CI 1.58–1.87), “unemployed” (OR 1.60; 95% CI 1.24–2.08), “short education” (OR 0.76; 95% CI 0.64–0.90), and lower income (beta-coefficient –26,121; 95% CI –37,931, –14,311). Hospital-diagnosed hyperhidrosis did not differ from controls. Thus, self-reported hyperhidrosis was associated with potential hyperhidrosis risk factors (smoking, overweight) and disease implications (unemployment, low education level and income)