title: The role of ketamine in treatment-resistant depression: a systematic review.
abstract: BACKGROUND
  At least 10-20% of the patients suffering from depression meet criteria for treatment-resistant depression (TRD). In the last decades, an important role of glutamate in mood modulation has been hypothesized and ketamine, a non noncompetitive antagonist of the N-methyl-D-aspartate (NMDA) receptors, has been demonstrated to be effective in both MDD and TRD. However, concerns emerged about the optimal dosage, and frequency of administration of this treatment.
  
  
  METHODS
  aiming to systematically review the current literature focusing on the main pharmacological properties and impact of ketamine in TRD, a detailed literature search in PubMed/Medline and ScienceDirect databases was conducted. Twenty-four manuscripts including a total of 416 patients fulfilled inclusion criteria.
  
  
  RESULTS
  Most studies demonstrated that the NMDA antagonist ketamine has rapid antidepressant effects in TRD patients, confirming the active role of glutamate in the pathophysiology of this complex condition. Ketamine has been demonstrated to be rapidly effective and was associated with a significant clinical improvement in depressive symptoms within hours after administration. Also, ketamine was also found to be effective in reducing suicidality in TRD samples.
  
  
  CONCLUSIONS
  The long-term efficacy of ketamine has not been investigated by most studies. The psychotomimetic properties may complicate the application of this pharmacological agent.
  
  
  CONCLUSIONS
  Ketamine may be considered a valid and intriguing antidepressant option for the treatment of TRD. Further studies are needed to evaluate its long-term antidepressant efficacy in patients with TRD.
authors.affiliation: Department of Neurosciences, Mental Health and Sensory Organs - Sant'Andrea Hospital, Sapienza University of Rome, Italy.
authors.forename: Gianluca
authors.initials: G
authors.lastname: Serafini
authors.affiliation: University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.
authors.forename: Robert H
authors.initials: RH
authors.lastname: Howland
authors.affiliation: Department of Neurosciences, Mental Health and Sensory Organs - Sant'Andrea Hospital, Sapienza University of Rome, Italy.
authors.forename: Fabiana
authors.initials: F
authors.lastname: Rovedi
authors.affiliation: Department of Neurosciences, Mental Health and Sensory Organs - Sant'Andrea Hospital, Sapienza University of Rome, Italy.
authors.forename: Paolo
authors.initials: P
authors.lastname: Girardi
authors.affiliation: Department of Neuroscience, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health, Section of Psychiatry, University of Genova, Genova, Italy.
authors.forename: Mario
authors.initials: M
authors.lastname: Amore
keywords: Antidepressant effect; NMDA receptors; ketamine; pharmacological properties; treatment-resistant depression.