title: Vortioxetine for major depressive disorder: a systematic review of the efficacy and safety profile for this newly approved antidepressant - what is the number needed to treat, number needed to harm and likelihood to be helped or harmed?
abstract: OBJECTIVE
  To describe the efficacy and safety of vortioxetine for the treatment of major depressive disorder (MDD).
  
  
  METHODS
  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.
  
  
  METHODS
  All available clinical reports of studies were identified.
  
  
  METHODS
  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.
  
  
  RESULTS
  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.
authors.affiliation: New York Medical College, Valhalla, NY, USA.
authors.forename: L
authors.initials: L
authors.lastname: Citrome
mesh_terms: D000328:Adult; D000368:Aged; D000928:Antidepressive Agents / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics; D001835:Body Weight / Q000187:drug effects; D002986:Clinical Trials as Topic; D003865:Major Depressive Disorder / Q000188:drug therapy*; D004334:Drug Administration Schedule; D005221:Fatigue / Q000139:chemically induced; D006801:Humans; D008875:Middle Aged; D061366:Numbers Needed To Treat; D064406:Patient Harm / Q000706:statistics & numerical data; D010879:Piperazines / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics; D055502:Secondary Prevention; D012735:Sexual Dysfunction, Physiological / Q000139:chemically induced; D013405:Suicide / Q000706:statistics & numerical data; D013440:Sulfides / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics; D016896:Treatment Outcome; D000078784:Vortioxetine
chemical_list: D000928:Antidepressive Agents; D010879:Piperazines; D013440:Sulfides; D000078784:Vortioxetine