INTRODUCTION: Vortioxetine is a structurally novel medication that has recently 
been approved for treatment of major depressive disorder (MDD). This medication 
is a serotonin reuptake inhibitor that also has a number of other potentially 
relevant effects on serotoninergic receptors, which may differentiate the drug's 
effects from those of current first-line antidepressants, such as selective 
serotonin reuptake inhibitors (SSRIs) and serotonin norepinephrine reuptake 
inhibitors (SNRIs).
AREAS COVERED: This article will review the basic clinical pharmacology of 
vortioxetine, summarize the major clinical trials that were performed prior to 
approval by the US Food and Drug Administration (FDA), discuss relevant 
post-marketing studies of this drug, and offer expert commentary on the 
significance of this new agent in clinical practice. Pre-approval studies were 
identified as all randomized, placebo-controlled studies of vortioxetine listed 
on clinicaltrials.gov. Other referenced studies were identified via a MEDLINE 
database literature search in August 2015 using the key search terms, 
vortioxetine and Lu AA21004, combined with additional terms that included 
pharmacological profile, pharmacokinetics, drug interactions, adverse effects, 
side effects, safety, major depression, and major depressive disorder. We 
identified relevant systematic reviews, meta-analyses, randomized trials and 
preclinical studies of importance.
EXPERT OPINION: Results of placebo-controlled trials suggest efficacy and an 
overall safety profile comparable to existing first-line antidepressants. The 
most common side effects are nausea, vomiting and constipation. Results of 
several studies indicate that vortioxetine may have therapeutic effects on 
cognition (e.g., memory and executive functioning) that exceed that of standard 
antidepressants. Disadvantages include cost and the current paucity of long-term 
efficacy data from large clinical trials. The authors suggest that vortioxetine 
is currently a good second-line antidepressant option and shows promise, pending 
additional long-term data, to become a first-line antidepressant option.