vortioxetine and Sexual-Dysfunction--Physiological

To describe the efficacy and safety of vortioxetine for the treatment of major depressive disorder (MDD).. The pivotal registration trials were accessed by querying http://www.ncbi.nlm.nih.gov/pubmed/, http://www.clinicaltrialsregister.eu and http://www.clinicaltrials.gov for the search terms 'vortioxetine' and 'Lu AA21004', and by obtaining posters presented at congresses. Product labelling provided additional information.. All available clinical reports of studies were identified.. Descriptions of the principal results and calculation of number needed to treat (NNT) and number needed to harm (NNH) for relevant dichotomous outcomes were extracted from the available study reports and other sources of information.. Vortioxetine is a multi-modal antidepressant that functions as a human 5-HT3A and 5-HT7 receptor antagonist, 5-HT1B receptor partial agonist, 5-HT1A receptor agonist, and inhibitor of the serotonin transporter. The recommended dose range is 5-20 mg/day. Approval for the treatment of MDD was based on a clinical development programme that included six positive 6-8 week studies, including one study in elderly people, and one positive maintenance study in adults. In the informative short-term studies in non-elderly patients, NNT for response with vortioxetine vs. placebo was 7 (95% CI 6-9), and NNT for remission vs. placebo was 11 (95% CI 8-17). NNH for discontinuation because of an adverse event (AE) was 36 (95% CI 24-70). The most commonly encountered AEs (incidence ≥ 5% and at least twice the rate of placebo) as identified in product labelling were nausea, constipation and vomiting, with NNH values vs. placebo of 6 (95% CI 6-7), 64 (95% CI 37-240), and 28 (95% CI 23-38), respectively. Changes in weight were not clinically relevant.. Vortioxetine represents another option for the treatment of MDD. Vortioxetine appears to have a favourable weight-gain profile. Additional information regarding the time course of response/remission and for the commonly occurring AE of nausea would be helpful to better characterise this agent. Pending clinical trials include those examining cognitive dysfunction that can accompany MDD.

Topics: Adult; Aged; Antidepressive Agents; Body Weight; Clinical Trials as Topic; Depressive Disorder, Major; Drug Administration Schedule; Fatigue; Humans; Middle Aged; Numbers Needed To Treat; Patient Harm; Piperazines; Secondary Prevention; Sexual Dysfunction, Physiological; Suicide; Sulfides; Treatment Outcome; Vortioxetine

Sexual dysfunction is prevalent among patients with depression, but assessment of treatment-emergent sexual dysfunction (TESD), a common side effect of antidepressants, can be confounded by the treatment of depressive symptoms in some patients.. To evaluate sexual functioning in healthy volunteers administered vortioxetine compared with paroxetine, an antidepressant known to cause sexual dysfunction, and placebo.. This phase 4, multicenter, randomized, double-blind, placebo-controlled, 4-arm, fixed-dose, head-to-head study compared sexual functioning in healthy volunteers administered vortioxetine (10 and 20 mg once daily [QD]), paroxetine (20 mg QD), or placebo for 5 weeks. Approximately equal numbers of men and women ages 18-40 years with normal sexual functioning (self-reported Changes in Sexual Functioning Questionnaire Short-Form [CSFQ-14] score > 47 for men; > 41 for women) were enrolled. Two modified full analysis sets adjusting for treatment non-compliance were prespecified.. The primary endpoint was change in CSFQ-14 total score for vortioxetine (10 and 20 mg) vs paroxetine after 5 weeks. Additional endpoints included CSFQ-14 change scores vs placebo, CSFQ-14 subscales, and patient global impression.. Of the 361 subjects enrolled (mean age, 28.4 years), approximately 57% were white, 34% black/African American, and 4% Asian. Vortioxetine 10 mg was associated with significantly less TESD than paroxetine (mean difference, +2.74 points; P = .009). Although vortioxetine 20 mg was associated with numerically less TESD than paroxetine (mean difference, +1.05 points), this difference did not reach statistical significance. Non-compliance appeared to influence results, particularly the paroxetine and vortioxetine 20 mg arms. Paroxetine, but not vortioxetine, was associated with statistically significantly more TESD vs placebo. Vortioxetine also had better outcomes than paroxetine in the 3 phases and 5 dimensions of sexual functioning measured by CSFQ-14.. These data establish that vortioxetine is associated with less TESD than paroxetine in healthy individuals, suggesting that vortioxetine may be a drug of choice in managing depressive disorders when sexual functioning is a concern.. Conducting the study in healthy adults mitigated the risk of an underlying condition (eg, depression) confounding the results. Assay sensitivity was demonstrated by statistically significant TESD with paroxetine vs placebo. The single comparator, paroxetine, and short study duration limit the generalizability of these results.. Vortioxetine is associated with less TESD than paroxetine in healthy adults across all phases and dimensions of the sexual response cycle. Vortioxetine was not significantly different from placebo on sexual functioning; however, the difference was significant between paroxetine and placebo, validating study results. Jacobsen P, Zhong W, Nomikos G, et al. Paroxetine, but not Vortioxetine, Impairs Sexual Functioning Compared With Placebo in Healthy Adults: A Randomized, Controlled Trial. J Sex Med 2019; 16:1638-1649.

Topics: Adolescent; Adult; Antidepressive Agents; Depressive Disorder, Major; Double-Blind Method; Female; Healthy Volunteers; Humans; Male; Paroxetine; Patient Compliance; Self Report; Sexual Behavior; Sexual Dysfunction, Physiological; Surveys and Questionnaires; Vortioxetine; Young Adult

Patients with major depressive disorder often experience relapse after responding to treatment; therefore, maintenance therapy with antidepressants is recommended for maintaining response or remission. This multicenter, open-label, flexible-dose, 52-week extension study evaluated the long-term safety, tolerability, and maintenance of efficacy in study participants who had completed one of two randomized, double-blind, placebo-controlled, 8-week dose-ranging vortioxetine trials in study participants with major depressive disorder. At the open-label baseline, all study participants were switched to vortioxetine 5 mg/day for the first week, with subsequent dose adjustments from 2.5 to 10 mg/day on the basis of response and tolerability. Treatment with vortioxetine for 52 weeks was well tolerated, with no new safety signals identified. Among the 834 evaluable study participants, treatment-emergent adverse events were reported in 70.6%, with the most common in the combined (all doses) population of nausea (15.2%), headache (12.4%), nasopharyngitis (9.8%), diarrhea (7.2%), and dizziness (6.8%). The rate of adverse events related to sexual dysfunction was low and weight gain was minimal. Laboratory values, vital signs, ECGs, physical examinations, and Columbia-Suicide Severity Rating Scale results showed no trends of clinical concern. The change in the severity of depressive and anxiety symptoms was maintained throughout the study as reflected by a 24-item Hamilton Depression Scale total score of 8.2 at week 52 (from 17.6 at open-label baseline) in the observed case data set.

Topics: Adult; Aged; Antidepressive Agents, Second-Generation; Anxiety; Depression; Depressive Disorder, Major; Double-Blind Method; Duloxetine Hydrochloride; Female; Humans; Male; Middle Aged; Piperazines; Psychiatric Status Rating Scales; Sexual Dysfunction, Physiological; Suicidal Ideation; Sulfides; Thiophenes; Treatment Outcome; Vortioxetine; Weight Gain; Young Adult

Vortioxetine (Lu AA21004) is an investigational antidepressant. In vitro studies indicate that vortioxetine is a 5-HT(3), 5-HT(7), and 5-HT(1D) receptor antagonist, 5-HT(1B) receptor partial agonist, 5-HT(1A) receptor agonist and inhibitor of the 5-HT transporter. This trial assessed the efficacy and tolerability of 2.5 and 5 mg vortioxetine for the treatment of MDD.. Adults (N = 611) with MDD were randomized to 8 weeks of double-blind treatment with placebo, vortioxetine (2.5 or 5 mg) or active reference (duloxetine 60 mg). The primary measure was change from baseline in the 24-item Hamilton Depression Scale (HAM-D24). Secondary endpoints included responder rate, Clinical Global Impression Scale-Global Improvement scale (CGI-I), and remission rate. Participants were monitored for adverse events (AEs), and treatment-emergent sexual dysfunction using the Arizona Sexual Experiences (ASEX) scale.. Both doses of vortioxetine were associated with declines in HAM-D24 total scores compared to placebo but were not statistically significant. At 8 weeks, changes from baseline were [mean (SE)]: -10.50 (0.76) placebo, -12.04 (0.74) 2.5 mg vortioxetine, and -11.08 (0.74) 5 mg vortioxetine. Secondary outcome measures in the vortioxetine groups, including responder rate, CGI-I, and remission rate, were also not significantly different from placebo. Duloxetine treatment was associated with declines in HAM-D24 total score [-13.47(0.75); p = 0.005] as well as significant improvements in secondary outcome measures versus placebo (p ≤ 0.05). The most common AEs for vortioxetine were nausea, dry mouth, and headache. Rates of sexual dysfunction (ASEX) were 51.0%, 37.5%, 46.9%, and 33.3% in the vortioxetine 2.5 mg, vortioxetine 5 mg, duloxetine, and placebo groups, respectively.. In this study of adults with MDD treated for 8 weeks with vortioxetine 2.5 mg or 5 mg per day, reductions in depression symptoms were not statistically significant compared with placebo. Study limitations are discussed, including patient characteristics, MDD severity, drug dosing, and aspects of trial design. Both doses of vortioxetine were well tolerated. This trial has been registered at clinicaltrials.gov #NCT00672620.

Topics: Adult; Antidepressive Agents; Depressive Disorder, Major; Double-Blind Method; Duloxetine Hydrochloride; Female; Humans; Male; Piperazines; Placebos; Sexual Dysfunction, Physiological; Suicidal Ideation; Sulfides; Thiophenes; Treatment Outcome; Vortioxetine

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

To analyze the impact of the antidepressant vortioxetine on sexual function, compared to selective serotonin reuptake inhibitors (SSRIs) and mixed selective serotonin and norepinephrine reuptake inhibitors (IRSN or Dual) in patients with depression.. Analytical, observational, longitudinal and prospective study, which included men and women over 18years of age, with depressive disorder and sexual activity with a partner, separating them into two groups: (i)study, starting treatment with vortioxetine; (2)control, maintaining treatment with SSRIs or Duals. Three visits were made: inclusion, follow-up at 4weeks and final 3months from inclusion. The total follow-up period was 3months.. A total of 87 patients were included (mean age 46.85years). At the end of the study, significant differences (SD) were found in the mean value of the sum of the scores of the evaluative domains of the sexual response of the Women's Sexual Function Questionnaire (FSM-2) between the study group and the control (22.42±4.39 and 16.13±7.76, respectively), with a lower risk of sexual dysfunction in women treated with vortioxetine. Also, lower risk of sexual dysfunction in these same women in the domains of desire, lubrication, orgasm, sexual frequency and sexual satisfaction. These differences were not found when assessing male sexual function.. Women treated with vortioxetine presented better sexual function than those treated with SSRIs or Duals and a lower risk of sexual dysfunction.

Topics: Adult; Antidepressive Agents; Depressive Disorder, Major; Female; Humans; Male; Middle Aged; Prospective Studies; Selective Serotonin Reuptake Inhibitors; Sexual Dysfunction, Physiological; Vortioxetine

Antidepressants are frequently associated with treatment-emergent sexual dysfunction (TESD). Vortioxetine, which was approved for patients with major depressive disorder (MDD), has a receptor profile that suggests limited impact on sexual functioning.. Arizona Sexual Experiences Scale (ASEX) patient-level data were pooled from 7 short-term vortioxetine trials (6 in MDD, 1 in generalized anxiety disorder) and analyzed for incidence of TESD at any post-baseline visit in patients without sexual dysfunction at baseline (defined as ASEX total score ≥19; individual ASEX item score ≥5; or a score ≥4 on any 3 ASEX items). The primary objective was to confirm the non-inferiority of vortioxetine 5-20 mg/day to placebo on the incidence of TESD. Comparisons were based on the common risk difference (95% confidence interval). Additional analyses compared vortioxetine to duloxetine and duloxetine to placebo. A sensitivity analysis, defined as TESD at 2 consecutive post-baseline visits, was conducted.. TESD incidence, relative to placebo, generally increased with vortioxetine dose with vortioxetine 5 mg non-inferior to placebo. Vortioxetine 10, 15, and 20 mg did not meet the non-inferiority criterion, but no dose had a significantly higher risk of developing TESD versus placebo. Changes in ASEX individual item scores supported the similarity of vortioxetine doses to placebo. Significantly higher TESD risk occurred with duloxetine 60 mg/day versus placebo and versus vortioxetine 5 or 10 mg. The sensitivity analysis was generally consistent with the primary analysis. Rates of spontaneously reported sexual adverse events were low.. Vortioxetine was associated with rates of TESD that were not significantly different from placebo in short-term clinical trials.

Topics: Adult; Anxiety Disorders; Depressive Disorder, Major; Female; Humans; Male; Middle Aged; Piperazines; Randomized Controlled Trials as Topic; Selective Serotonin Reuptake Inhibitors; Sexual Dysfunction, Physiological; Sexual Dysfunctions, Psychological; Sulfides; Vortioxetine