vortioxetine and Nausea

Major depressive disorder (MDD) is a highly prevalent and burdensome condition. This study aims to evaluate the effectiveness, tolerability, and safety of vortioxetine in treating MDD based on real-world data.. A systematic search of 8 electronic databases was performed from inception until October 2022 to identify real-world studies, excluding randomized controlled trials. We conducted subgroup, meta-regression, sensitivity analyses, publication bias, and quality assessments using the random-effects model. The effects were summarized by rates or standardized mean difference (SMD) with 95% confidence interval (CI).. Of the 870 records identified, 11 studies (3139 participants) and 10 case reports or series were eligible for inclusion. Vortioxetine significantly relieved depression symptoms as assessed by both patients (SMD = 2.25, 95% CI = 1.60-2.89) and physicians (SMD = 3.73, 95% CI = 2.78-4.69). Cognitive function (SMD =1.86, 95% CI = 1.11-2.62) and functional disability (SMD =1.71, 95% CI = 1.14-2.29) were similarly markedly improved. Subgroup and meta-regression analyses showed that geographic location and medication regimen (whether combined with other antidepressants) were crucial factors influencing effectiveness (in terms of depression severity and cognitive function), potentially contributing to significant heterogeneity. The estimated response and remission rates were 66.4% (95% CI = 51.2%-81.5%) and 58.0% (95% CI = 48.9%-67.1%), respectively. Vortioxetine was well tolerated, with a pooled dropout rate of 3.5% (95% CI = 1.8%-5.8%), and the most common adverse event was nausea, with an estimated rate of 8.9% (95% CI = 3.8%-15.8%).. The study has some limitations, including significant heterogeneity and limited evidence for some outcomes.. Vortioxetine is effective, well tolerated, and safe for treating MDD in clinical practice, with significant improvements observed in depressive severity, cognitive function, and functioning. Future studies should directly compare vortioxetine with other antidepressants in real-world settings to further evaluate its clinical utility.

Topics: Antidepressive Agents; Cognition; Depressive Disorder, Major; Humans; Nausea; Vortioxetine

There is a growing interest in vortioxetine in major depressive disorder (MDD).. This meta-analysis aimed to assess the efficacy and safety of 10 mg/day (mg/d) vortioxetine compared to placebo for MDD in adult.. Eight randomly controlled trials (RCTs) about the treatment of 10 mg/d vortioxetine in adult patients with MDD were identified and 2354 patients were included in meta-analysis.. According to the results, 10 mg/d vortioxetine showed significant differences in response rates (OR=1.88, 95% CI=1.40-2.53, P<0.0001), remission rates (OR=1.54, 95% CI=1.27-1.86, P<0.00001), change from baseline in Montgomery-Asberg Depression Rating Scale (MADRS) total score (SMD=-3.50, 95%CI=-4.83 to -2.17, P<0.00001), clinical global Impression-Global Improvement (CGI-I) total score (SMD=-3.40, 95% CI=-4.69 to -2.11, P<0.00001), and change from baseline in Sheehan Disability Scale (SDS) total score (SMD=-2.09, 95% CI=-2.64 to -1.55, P<0.00001). But 10 mg/d vortioxetine was easier induced nausea (OR=4.18, 95% CI=3.21-5.44, P<0.00001) and constipation (OR=1.88, 95% CI=1.14 to 3.09, P=0.01).. 10 mg/d vortioxetine was more effective, but easily induced nausea and constipation when compared to placebo for MDD in adult.

Topics: Antidepressive Agents; Constipation; Depressive Disorder, Major; Humans; Nausea; Placebos; Randomized Controlled Trials as Topic; Treatment Outcome; Vortioxetine

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

Vortioxetine is a structurally novel medication that has recently been approved for treatment of major depressive disorder (MDD). This medication is a serotonin reuptake inhibitor that also has a number of other potentially relevant effects on serotoninergic receptors, which may differentiate the drug's effects from those of current first-line antidepressants, such as selective serotonin reuptake inhibitors (SSRIs) and serotonin norepinephrine reuptake inhibitors (SNRIs).. This article will review the basic clinical pharmacology of vortioxetine, summarize the major clinical trials that were performed prior to approval by the US Food and Drug Administration (FDA), discuss relevant post-marketing studies of this drug, and offer expert commentary on the significance of this new agent in clinical practice. Pre-approval studies were identified as all randomized, placebo-controlled studies of vortioxetine listed on clinicaltrials.gov. Other referenced studies were identified via a MEDLINE database literature search in August 2015 using the key search terms, vortioxetine and Lu AA21004, combined with additional terms that included pharmacological profile, pharmacokinetics, drug interactions, adverse effects, side effects, safety, major depression, and major depressive disorder. We identified relevant systematic reviews, meta-analyses, randomized trials and preclinical studies of importance.. Results of placebo-controlled trials suggest efficacy and an overall safety profile comparable to existing first-line antidepressants. The most common side effects are nausea, vomiting and constipation. Results of several studies indicate that vortioxetine may have therapeutic effects on cognition (e.g., memory and executive functioning) that exceed that of standard antidepressants. Disadvantages include cost and the current paucity of long-term efficacy data from large clinical trials. The authors suggest that vortioxetine is currently a good second-line antidepressant option and shows promise, pending additional long-term data, to become a first-line antidepressant option.

Topics: Animals; Antidepressive Agents; Constipation; Depressive Disorder, Major; Humans; Nausea; Piperazines; Randomized Controlled Trials as Topic; Selective Serotonin Reuptake Inhibitors; Sulfides; Vomiting; Vortioxetine

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

Vortioxetine is the first mixed serotonin agonist and antagonist antidepressant approved in the US. We sought to evaluate all published and unpublished data available to determine the efficacy and harms of vortioxetine in adults with major depressive disorder.. We used a predefined search strategy of MEDLINE, the Cochrane Central Register of Controlled Trials, ClinicalTrials.gov, and Drugs@FDA to identify studies evaluating vortioxetine in the acute treatment of major depressive disorder. Only randomized controlled trials (RCTs) that provided results on relevant clinical efficacy and safety outcomes were included. Study quality was assessed and results were pooled using mixed effect meta-analyses where applicable.. We identified 11 RCTs with 6,145 participants meeting inclusion criteria (eight were published and three were unpublished). The trials did not exceed 8 weeks in duration. The response rate with vortioxetine was significantly higher for 1-mg (relative risk (RR) = 1.91; 95% confidence interval (CI) 1.36 to 2.69), 5-mg (RR = 1.33; 95% CI 1.10 to 1.61), 10-mg (RR = 1.42; 95% CI 1.21 to 1.67), and 20-mg doses (RR = 1.58; 95% CI 1.19 to 2.08) compared to placebo. Remission rates were significantly higher for the 10-mg group (RR = 1.45; 95% CI 1.18 to 1.77) and the 20-mg group (RR = 1.68; 95% CI 1.19 to 2.37) compared to placebo. Meta-regression of dose on the log odds ratio of response was not statistically significant (β = 0.01; P = 0.46). Vortioxetine response rates were lower than active serotonin and norepinephrine reuptake inhibitor (SNRI) comparators for the 5-mg (RR = 0.88; 95% CI 0.80 to 0.98), 15-mg (RR = 0.78; 95% CI 0.68 to 0.90), and 20-mg (RR = 0.82; 95% CI 0.72 to 0.94) doses. The most common adverse events were nausea and vomiting which increased in frequency with higher doses.. Vortioxetine was significantly more effective than placebo for acute treatment of major depressive disorder (MDD). Although treatment effect estimates varied substantially between studies, a dose effect was not observed. Vortioxetine does not appear to be more effective, and is potentially less effective, than an SNRI.. PROSPERO CRD42013006198 .

Topics: Adult; Antidepressive Agents; Depressive Disorder, Major; Humans; Nausea; Outcome Assessment, Health Care; Piperazines; Serotonin Agents; Sulfides; Vomiting; Vortioxetine

This 7-day randomized, double-blind, placebo-controlled fixed-dose study (NCT03766867) explored the potential for accelerating the onset of antidepressant efficacy of single-dose intravenous (IV) vortioxetine at oral vortioxetine treatment initiation. Patients (ages 18-65 years) hospitalized per standard-of-care with major depressive disorder, who were currently treated with a selective serotonin reuptake inhibitor or serotonin-norepinephrine reuptake inhibitor for a major depressive episode [Montgomery-Åsberg Depression Rating Scale (MADRS) total score ≥ 30], received one dose of single-blind IV placebo (1-day placebo lead-in period) before being randomly switched to either single-dose IV vortioxetine 25 mg plus daily oral vortioxetine 10 mg (n = 39), or IV placebo plus daily oral placebo (n = 41). In the placebo lead-in period, patients improved slightly by 0.6 MADRS-6 point; however, at day 1 after randomization, both treatment groups had improved by approximately 3 MADRS-6 points (mean difference = -0.8; P = 0.263), the study thus not meeting its primary endpoint. Similar results were seen for other outcomes except a numerically larger improvement in anxiety symptoms with vortioxetine vs placebo. Pharmacokinetic data confirmed that IV vortioxetine facilitated reaching steady-state plasma concentration within 24 h. IV plus oral vortioxetine was well tolerated, with low levels of nausea as the most common adverse event.

Topics: Administration, Intravenous; Administration, Oral; Adult; Aged; Antidepressive Agents; Depressive Disorder, Major; Double-Blind Method; Humans; Male; Middle Aged; Nausea; Selective Serotonin Reuptake Inhibitors; Vortioxetine

Residual cognitive symptoms in major depressive disorder (MDD) are common, yet poorly investigated. We explored the effectiveness of vortioxetine as adjunctive treatment to selective serotonin reuptake inhibitors (SSRI) and as monotherapy versus continued SSRI, in patients with MDD who achieved full or partial remission with SSRI, but report residual cognitive symptoms.. Patients (18-65 years old, N =151) diagnosed with MDD, with a Hamilton Depression Rating Scale 17-items total score ≤10 and a Perceived Deficits Questionnaire-Depression total score >25, were randomized 1:1:1 to 8 weeks of double-blind treatment with current SSRI + placebo, SSRI + vortioxetine (10-20 mg/day), or vortioxetine (10-20 mg/day) + placebo. The primary efficacy measure was the Digit Symbol Substitution Test (DSST), analyzed using a mixed model for repeated measurements. Secondary outcomes comprised cognitive functioning, subjectively-rated cognitive symptoms, patient functioning, and mood symptoms.. From baseline to week 8, all treatment groups improved DSST performance, with statistically nonsignificant treatment differences. Similar results were seen for secondary endpoints. Improvement in cognitive performance tended to be numerically larger with vortioxetine monotherapy than with SSRI monotherapy, while vortioxetine as adjunctive treatment tended to perform numerically better in further improving depressive symptoms. Most adverse events were mild or moderate. Nausea was the most common adverse event for vortioxetine.. Small sample sizes limited statistical power.. In this explorative study, remitted patients with MDD improved their cognitive performance with no treatment differences. Secondary results indicate numerical benefits for cognitive performance with vortioxetine monotherapy, and for depressive symptoms with vortioxetine augmentation.

Topics: Adolescent; Adult; Aged; Antidepressive Agents; Cognition; Depressive Disorder, Major; Double-Blind Method; Drug Therapy, Combination; Female; Humans; Male; Middle Aged; Nausea; Selective Serotonin Reuptake Inhibitors; Surveys and Questionnaires; Treatment Outcome; Vortioxetine; Young Adult

This 2-week randomized, double-blind, placebo-controlled fixed-dose study (NCT02919501) explored the potential of accelerating onset of antidepressant efficacy and plasma exposure with single-dose intravenous vortioxetine at oral vortioxetine treatment initiation. Outpatients (ages 18-65 years) with major depressive disorder and a current depressive episode (Montgomery Åsberg Depression Rating Scale total score ≥30) were randomized to an initial single dose of either intravenous vortioxetine 17 mg (n = 27) or intravenous placebo (n = 28), both treatments followed by 2 weeks of oral vortioxetine (10 mg/day). From baseline to day 7, both groups exhibited fast and substantial improvements by approximately 14 Montgomery Åsberg Depression Rating Scale points, with no statistically significant treatment difference for this primary endpoint. Improvements were substantial already within 24 hours, with numerical treatment differences of 1.3 and 1.6 points at days 1 and 3, respectively, in favour of intravenous vortioxetine + oral vortioxetine. Pharmacokinetic data confirmed that intravenous vortioxetine facilitated reaching steady-state plasma concentration within 24 hours. Intravenous vortioxetine + oral vortioxetine was safe and well-tolerated, with nausea as the most common adverse event. This study supported intravenous vortioxetine as a means of rapidly reaching therapeutic vortioxetine blood levels.

Topics: Adolescent; Adult; Aged; Antidepressive Agents; Depressive Disorder, Major; Double-Blind Method; Female; Humans; Male; Middle Aged; Nausea; Psychiatric Status Rating Scales; Selective Serotonin Reuptake Inhibitors; Serotonin 5-HT1 Receptor Agonists; Serotonin 5-HT3 Receptor Antagonists; Treatment Outcome; Vortioxetine; Young Adult

Major Depressive Disorder (MDD) is a complex disease characterized by emotional, physical and cognitive symptoms. We explored the efficacy of vortioxetine versus placebo on outcomes of cognition, functioning and mood symptoms in working patients with depression, using paroxetine as an active reference.. Gainfully employed patients (18-65 years, N = 152) with MDD were randomized 1:1:1 to 8 weeks' double-blind, parallel treatment either with vortioxetine (10mg/day) or paroxetine (20mg/day), or with placebo. The primary efficacy measure was the Digit Symbol Substitution Test (DSST), analyzed using a mixed model for repeated measurements, and the key secondary efficacy measure was the University of San Diego Performance-based Skills Assessment - Brief (UPSA-B), analyzed using analysis of covariance (last observation carried forward).. At week 8, DSST and UPSA-B performance had improved relative to baseline in all treatment groups, with no statistically significant differences between treatment groups. While improvements in mood were comparable for vortioxetine and paroxetine, numerical improvements in cognitive performance (DSST) were larger with vortioxetine. Vortioxetine significantly improved overall cognitive performance and clinician-rated functioning relative to placebo. The majority of adverse events were mild or moderate, with nausea being the most common adverse event for vortioxetine.. Small sample sizes implied limited statistical power.. This explorative study showed no significant differences versus placebo in DSST or UPSA-B performance at week 8. However, secondary results support vortioxetine as an effective and well-tolerated antidepressant, supporting an added benefit for cognition and functioning, which could have particular therapeutic relevance for the working patient population.

Topics: Adult; Antidepressive Agents; Cognition; Depressive Disorder, Major; Dose-Response Relationship, Drug; Double-Blind Method; Female; Humans; Male; Middle Aged; Nausea; Paroxetine; Piperazines; Sulfides; Treatment Outcome; Vortioxetine; Wechsler Scales

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