vortioxetine and Fatigue

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

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

Vortioxetine has reduced depressive symptoms in adults with major depressive disorder (MDD) in multiple clinical trials.. The aim of this study is to evaluate the efficacy, safety, and tolerability of vortioxetine 15 and 20 mg vs placebo in adults with MDD.. Patients were randomized 1:1:1:1 to vortioxetine 15 mg, vortioxetine 20 mg, duloxetine 60 mg (active reference), or placebo. The primary efficacy endpoint was mean change in Montgomery-Åsberg Depression Rating Scale (MADRS) total score at week 8 (MMRM). Safety/tolerability assessments included physical examinations, vital signs, laboratory evaluations, electrocardiograms, adverse events (AEs), Columbia-Suicide Severity Rating Scale, Arizona Sexual Experiences Scale, and Discontinuation-Emergent Signs and Symptoms checklist.. Six hundred and fourteen patients were randomized. Mean changes in MADRS scores were -12.83 (±0.834), -14.30 (±0.890), -15.57 (±0.880), and -16.90 (±0.884) for placebo, vortioxetine 15 mg (P = .224), vortioxetine 20 mg (P = .023), and duloxetine 60 mg (P < .001) (P vs placebo), respectively. AEs reported by ≥5 % of vortioxetine patients included nausea, headache, diarrhea, dizziness, dry mouth, constipation, vomiting, insomnia, fatigue, and upper respiratory infection. Treatment-emergent sexual dysfunction, suicidal ideation or behavior, and discontinuation symptoms were not significantly different between vortioxetine and placebo.. Vortioxetine 20 mg significantly reduced MADRS total scores after 8 weeks of treatment. Both vortioxetine doses were well tolerated.. ClinicalTrials.gov identifier NCT01153009; www.clinicaltrials.gov/ .

Topics: Adolescent; Adult; Aged; Antidepressive Agents; Depressive Disorder, Major; Dose-Response Relationship, Drug; Double-Blind Method; Duloxetine Hydrochloride; Electrocardiography; Fatigue; Female; Humans; Male; Middle Aged; Piperazines; Psychiatric Status Rating Scales; Selective Serotonin Reuptake Inhibitors; Sleep Initiation and Maintenance Disorders; Suicidal Ideation; Sulfides; Vortioxetine; Young Adult