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

The safety and tolerability of vortioxetine: analysis of data from randomised placebo-controlled trials and open-label extension studies
The safety and tolerability of vortioxetine: analysis of data from randomised placebo-controlled trials and open-label extension studies
The safety and tolerability of vortioxetine in adults with major depressive disorder (MDD) 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 randomised, double-blind placebo-controlled short-term studies in MDD: 6 with an active reference. Symptoms following discontinuation were assessed through the Discontinuation-Emergent Signs and Symptoms (DESS) checklist in 3 studies. Long-term (?52 weeks) tolerability was evaluated in 5 open-label extension studies. 5701 patients 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 to placebo (3.6%), venlafaxine XR (14.2%) or duloxetine (8.8%). Common TEAEs (incidence ?5% and >2x 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 DESS 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 MDD.
major depressive disorder, safety, tolerability, vortioxetine
0269-8811
242-252
Baldwin, David
1beaa192-0ef1-4914-897a-3a49fc2ed15e
Chrones, Lambros
873f83c6-3bf6-4e17-8293-b1a96d64266b
Ioana, Florea
8c58806a-0066-4026-b664-8c6eafbc9c80
Nielsen, Rebecca
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Nomikos, George
a4355132-d746-492a-8910-6baff200469b
Palo, William
ab1a63a3-498a-452b-ae87-4238e09c976b
Reines, Elin
7e81c23d-0bb8-4162-847d-c7c0f25575b9
Baldwin, David
1beaa192-0ef1-4914-897a-3a49fc2ed15e
Chrones, Lambros
873f83c6-3bf6-4e17-8293-b1a96d64266b
Ioana, Florea
8c58806a-0066-4026-b664-8c6eafbc9c80
Nielsen, Rebecca
9659f4de-fa64-4fd4-90a4-74f85a5cf7e3
Nomikos, George
a4355132-d746-492a-8910-6baff200469b
Palo, William
ab1a63a3-498a-452b-ae87-4238e09c976b
Reines, Elin
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Baldwin, David, Chrones, Lambros, Ioana, Florea, Nielsen, Rebecca, Nomikos, George, Palo, William and Reines, Elin (2016) The safety and tolerability of vortioxetine: analysis of data from randomised placebo-controlled trials and open-label extension studies. Journal of Psychopharmacology, 30 (3), 242-252. (doi:10.1177/0269881116628440). (PMID:26864543)

Record type: Article

Abstract

The safety and tolerability of vortioxetine in adults with major depressive disorder (MDD) 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 randomised, double-blind placebo-controlled short-term studies in MDD: 6 with an active reference. Symptoms following discontinuation were assessed through the Discontinuation-Emergent Signs and Symptoms (DESS) checklist in 3 studies. Long-term (?52 weeks) tolerability was evaluated in 5 open-label extension studies. 5701 patients 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 to placebo (3.6%), venlafaxine XR (14.2%) or duloxetine (8.8%). Common TEAEs (incidence ?5% and >2x 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 DESS 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 MDD.

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Accepted/In Press date: 4 January 2016
e-pub ahead of print date: 9 February 2016
Published date: 23 February 2016
Keywords: major depressive disorder, safety, tolerability, vortioxetine
Organisations: Clinical & Experimental Sciences

Identifiers

Local EPrints ID: 385947
URI: https://eprints.soton.ac.uk/id/eprint/385947
ISSN: 0269-8811
PURE UUID: 1065168a-010b-4b5a-a9b4-66961817dc39

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Date deposited: 26 Jan 2016 15:16
Last modified: 09 Jan 2018 18:15

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Contributors

Author: David Baldwin
Author: Lambros Chrones
Author: Florea Ioana
Author: Rebecca Nielsen
Author: George Nomikos
Author: William Palo
Author: Elin Reines

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