PMID- 29736744
OWN - NLM
STAT- MEDLINE
DCOM- 20190617
LR  - 20190617
IS  - 1179-1934 (Electronic)
IS  - 1172-7047 (Linking)
VI  - 32
IP  - 5
DP  - 2018 May
TI  - Antidepressant Efficacy and Tolerability of Ketamine and Esketamine: A Critical 
      Review.
PG  - 411-420
LID - 10.1007/s40263-018-0519-3 [doi]
AB  - Ketamine and its enantiomer S-ketamine (esketamine) are promising candidates to 
      produce a rapid-onset antidepressant effect in treatment-resistant depression. 
      Ketamine causes continued blockade of the glutamate N-methyl-D-aspartate (NMDA) 
      receptor, though this might not primarily mediate the antidepressant effect. 
      Alternative hypotheses include selectivity for the NMDA receptor subtype 
      containing the NMDA receptor subunit 2B (NR2B), inhibition of the phosphorylation 
      of the eukaryotic elongation factor 2 (eEF2) kinase, increased expression of 
      brain-derived neurotrophic factor (BDNF) and tropomyosin receptor kinase B 
      (TrKB), and activation of the mammalian target of rapamycin (mTOR) signaling 
      pathway, alongside other independent actions attributed to the ketamine 
      metabolism to R-hydroxynorketamine (R-HNK). The enantiomer S-ketamine 
      (esketamine) displays approximately fourfold greater affinity for the glutamate 
      NMDA receptor in vitro than R-ketamine. Proof-of-concept single-dose and 
      repeat-dose studies with intravenous ketamine show a significant antidepressant 
      and probably antisuicidal effect in the short term, with response rates over 60% 
      as early as 4.5 h after a single dose, with a sustained effect after 24 h, and 
      over 40% after 7 days. This response can be further sustained over several weeks 
      with repeated doses (two to three doses per week). Tolerability seems acceptable 
      in the short term, with transient elevation of blood pressure and mild and 
      transient dissociative and psychotomimetic effects. Intranasal esketamine has 
      shown a comparable antidepressant effect, which has resulted in the US FDA 
      granting the drug a "breakthrough therapy" designation, and theoretically it may 
      offer an improved tolerability profile. However, major concerns remain regarding 
      an effective protocol to maintain the clinical antidepressant effect of ketamine 
      seen with acute administration and the safety of ketamine and esketamine in the 
      long term, specifically related to potential neurocognitive and urologic 
      toxicity, together with the potential induction of substance use disorders. 
      Ketamine and esketamine are not currently approved treatments for depression, but 
      the clinical use of ketamine is increasing in a variety of practice settings 
      internationally.
FAU - Molero, P
AU  - Molero P
AUID- ORCID: 0000-0002-9287-9635
AD  - Department of Psychiatry, Instituto de Investigacion Sanitaria de Navarra 
      (IdiSNA), University Clinic of Navarra, 31008, Pamplona, Spain. pmolero@unav.es.
FAU - Ramos-Quiroga, J A
AU  - Ramos-Quiroga JA
AD  - Department of Psychiatry, Hospital Universitari Vall d'Hebron, CIBERSAM, 
      Barcelona, Catalonia, Spain.
AD  - Department of Psychiatry and Forensic Medicine, Universitat Autonoma de 
      Barcelona, Barcelona, Catalonia, Spain.
FAU - Martin-Santos, R
AU  - Martin-Santos R
AD  - Department of Psychiatry and Psychology, Hospital Clinic, IDIBAPS, CIBERSAM, 
      Institute of Neuroscience, University of Barcelona, Barcelona, Spain.
FAU - Calvo-Sanchez, E
AU  - Calvo-Sanchez E
AD  - Department of Psychiatry, Hospital Universitari Vall d'Hebron, CIBERSAM, 
      Barcelona, Catalonia, Spain.
AD  - Department of Psychiatry and Forensic Medicine, Universitat Autonoma de 
      Barcelona, Barcelona, Catalonia, Spain.
FAU - Gutierrez-Rojas, L
AU  - Gutierrez-Rojas L
AD  - Psychiatry and Neurosciences Research Group (CTS-549), Institute of 
      Neurosciences, University of Granada, Granada, Spain.
FAU - Meana, J J
AU  - Meana JJ
AD  - Department of Pharmacology, University of the Basque Country, UPV/EHU, CIBERSAM, 
      Leioa, Bizkaia, Spain.
AD  - Biocruces Health Research Institute, Barakaldo, Bizkaia, Spain.
LA  - eng
PT  - Journal Article
PT  - Review
PL  - New Zealand
TA  - CNS Drugs
JT  - CNS drugs
JID - 9431220
RN  - 0 (Antidepressive Agents)
RN  - 50LFG02TXD (Esketamine)
RN  - 690G0D6V8H (Ketamine)
SB  - IM
MH  - Animals
MH  - Antidepressive Agents/*adverse effects/pharmacology/*therapeutic use
MH  - Humans
MH  - Ketamine/*adverse effects/pharmacology/*therapeutic use
EDAT- 2018/05/08 06:00
MHDA- 2019/06/18 06:00
CRDT- 2018/05/09 06:00
PHST- 2018/05/08 06:00 [pubmed]
PHST- 2019/06/18 06:00 [medline]
PHST- 2018/05/09 06:00 [entrez]
AID - 10.1007/s40263-018-0519-3 [pii]
AID - 10.1007/s40263-018-0519-3 [doi]
PST - ppublish
SO  - CNS Drugs. 2018 May;32(5):411-420. doi: 10.1007/s40263-018-0519-3.