The safety and tolerability of vortioxetine: Analysis of data from randomized placebo-controlled trials and open-label extension studies

Abstract

The safety and tolerability of vortioxetine in adults with major depressive disorder was assessed. Tolerability was based on the nature, incidence and severity of treatment-emergent adverse events (TEAEs) during acute (6/8) week treatment in 11 randomized, double-blind placebo-controlled short-term studies in major depressive disorder: six with an active reference. Symptoms following discontinuation were assessed through the Discontinuation-Emergent Signs and Symptoms checklist in three studies. Long-term (⩽52 weeks) tolerability was evaluated in five open-label extension studies. Patients (n =5701) were acutely treated with either placebo (n=1817), vortioxetine (5–20mg/day; n=3018), venlafaxine XR (225mg/day; n=113) or duloxetine (60mg/day; n=753). The withdrawal rate due to TEAEs during treatment with vortioxetine (5–20mg/day) was 4.5–7.8%, compared with placebo (3.6%), venlafaxine XR (14.2%) or duloxetine (8.8%). Common TEAEs (incidence ⩾5% and >2 × placebo) with vortioxetine (5–20mg/day) were nausea (20.9–31.2%) and vomiting (2.9–6.5%). For vortioxetine (5–20mg/day), the incidence of TEAEs associated with insomnia was 2.0–5.1% versus 4.0% for placebo, and with sexual dysfunction 1.6–1.8% versus 1.0% for placebo. Discontinuation symptoms as assessed by the mean Discontinuation-Emergent Signs and Symptoms total score after abrupt discontinuation were comparable to placebo in the first and second week. Vortioxetine had no effect relative to placebo on clinical laboratory parameters, body weight, heart rate or blood pressure. Vortioxetine showed no clinically relevant effect on ECG parameters, including the QTcF interval. In long-term treatment, no new types of TEAEs were seen; the mean weight gain was 0.7–0.8kg. Thus, vortioxetine (5–20mg/day) appears safe and generally well tolerated in the treatment of major depressive disorder.

Vortioxetine-induced nausea and its management

“…For vortioxetine, the most common treatment-emergent adverse events leading to withdrawal was nausea. Nausea was most often transient, with a median duration of 9-16 days, for doses from 5 to 20 mg/day [4]. The rates of serious adverse events were similar at all dosing levels when compared to the SNRI group.…”

Guidelines of the Polish Psychiatric Association – Wroclaw Division, the Polish Society of Family Medicine and the College of Family Physicians in Poland for diagnosis and treatment of depressive disorders in primary health care

“…as research suggest, patients' expectations for the behavior of a physician are different. according to zimmer- Paroxetine 20 mg [76] moclobemide 300 mg (i-mao-a) [77] sertraline 50 mg [78] trazodone 150 mg (sari) [79] Venlafaxine 75 mg (snri) [80] amitriptyline 75 mg (tCa) [81] Clomipramine 150 mg (tCa) [82] opipramol 200 mg (tCa) [83] doxepine 100 mg (tCa) [84] Vortioxetine 10 mg (sms) [85] Bupropion 150 mg (ndri) [86] man et al, the importance of patients' expectations is as follows: 1) the presence of mental health symptoms (e.g. optimism, vigor, self-confidence); 2) sense of normality; 3) return to normal functioning at work, home; 4) the feeling of emotional control; 5) relationships with family and friends and the ability to enjoy them; 6) the lack of symptoms of depression -as the last element of the psychopathological picture [87].…”

Panic psychosis: paroxysmal panic anxiety concomitant with auditory hallucinations in schizophrenia

“…Veras et al 2 described a cognitiveaffective link between panic attacks and psychosis, pointing to the influence of the experience of helplessness on the symptoms of psychotic patients who experience highly intense auditory hallucinations and panic attacks. Freeman & Fowler 3 and Ruby et al 4 described the importance of traumatic events as a common etiological element and connector between anxiety and psychosis. An important psychological contribution to psychiatric disorders is impaired psychological development during childhood.…”