OBJECTIVE: To describe the efficacy and safety of vortioxetine for the treatment 
of major depressive disorder (MDD).
DATA SOURCES: 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.
STUDY SELECTION: All available clinical reports of studies were identified.
DATA EXTRACTION: 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.
DATA SYNTHESIS: 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.
CONCLUSIONS: 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.