PMID- 24688759
OWN - NLM
STAT- PubMed-not-MEDLINE
DCOM- 20140624
LR  - 20220321
IS  - 2045-1253 (Print)
IS  - 2045-1261 (Electronic)
IS  - 2045-1253 (Linking)
VI  - 4
IP  - 2
DP  - 2014 Apr
TI  - Ketamine as the prototype glutamatergic antidepressant: pharmacodynamic actions, 
      and a systematic review and meta-analysis of efficacy.
PG  - 75-99
LID - 10.1177/2045125313507739 [doi]
AB  - The burden of depressive disorders and the frequent inadequacy of their current 
      pharmacological treatments are well established. The anaesthetic and 
      hallucinogenic drug ketamine has provoked much interest over the past decade or 
      so as an extremely rapidly acting antidepressant that does not modify 'classical' 
      monoaminergic receptors. Current evidence has shown several ways through which it 
      might exert therapeutic antidepressant actions: blockade of glutamatergic NMDA 
      receptors and relative upregulation of 
      alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) subtypes may alter 
      cortical connectivity patterns; through intracellular changes in protein 
      expression, including the proteins mammalian target of rapamycin (mTOR) and 
      brain-derived neurotrophic factor (BDNF); and alteration of intracellular 
      signalling cascades. The clinical evidence demonstrates rapid improvements in 
      mood and suicidal thinking in most participants, although study numbers have 
      generally been small and many trials are unblinded and methodologically weak. 
      There is a small body of work to suggest ketamine might also augment 
      electroconvulsive therapy and potentially have a role as a surgical anaesthetic 
      in depressed patients. A major problem is that the effects of ketamine appear 
      temporary, disappearing after days to weeks (although longer benefits have been 
      sustained in some), and attempts to circumvent this through pharmacological 
      augmentation have been disappointing thus far. These exciting data are providing 
      new insights into neurobiological models of depression, and potentially opening 
      up a new class of antidepressants, but there are significant practical and 
      ethical issues about any future mainstream clinical role it might have.
FAU - Caddy, Caroline
AU  - Caddy C
AD  - Cognition Schizophrenia and Imaging Laboratory, Department of Psychosis Studies, 
      the Institute of Psychiatry, King's College London, UK.
FAU - Giaroli, Giovanni
AU  - Giaroli G
AD  - Cognition Schizophrenia and Imaging Laboratory, Department of Psychosis Studies, 
      the Institute of Psychiatry, King's College London, UK and North East London NHS 
      Foundation Trust, London, UK.
FAU - White, Thomas P
AU  - White TP
AD  - Cognition Schizophrenia and Imaging Laboratory, Department of Psychosis Studies, 
      the Institute of Psychiatry, King's College London, UK.
FAU - Shergill, Sukhwinder S
AU  - Shergill SS
AD  - Cognition Schizophrenia and Imaging Laboratory, Department of Psychosis Studies, 
      the Institute of Psychiatry, King's College London, UK and South London and 
      Maudsley NHS Foundation Trust, London, UK.
FAU - Tracy, Derek K
AU  - Tracy DK
AD  - Consultant Psychiatrist, Oxleas NHS Foundation Trust, Princess Royal University 
      Hospital, Orpington, BR6 8NY, UK and Cognition Schizophrenia and Imaging 
      Laboratory, Department of Psychosis Studies, the Institute of Psychiatry, King's 
      College London, UK.
LA  - eng
GR  - G0901868/MRC_/Medical Research Council/United Kingdom
PT  - Journal Article
PT  - Review
PL  - England
TA  - Ther Adv Psychopharmacol
JT  - Therapeutic advances in psychopharmacology
JID - 101555693
PMC - PMC3952483
OTO - NOTNLM
OT  - antidepressant
OT  - glutamatergic
OT  - ketamine
COIS- Conflict of interest statement: Derek Tracy has received honoraria for 
      educational talks from Lilly UK and Roche UK. Sukhwinder Shergill has received 
      grant support from clinical trials from GlaxoSmithKline, Roche, Abbvie and 
      Envivo, and has served as consultant, scientific advisor and had speaking 
      engagements for Sunovion, Roche and Dainippon Sumitomo Pharma.
EDAT- 2014/04/02 06:00
MHDA- 2014/04/02 06:01
PMCR- 2014/04/01
CRDT- 2014/04/02 06:00
PHST- 2014/04/02 06:00 [entrez]
PHST- 2014/04/02 06:00 [pubmed]
PHST- 2014/04/02 06:01 [medline]
PHST- 2014/04/01 00:00 [pmc-release]
AID - 10.1177_2045125313507739 [pii]
AID - 10.1177/2045125313507739 [doi]
PST - ppublish
SO  - Ther Adv Psychopharmacol. 2014 Apr;4(2):75-99. doi: 10.1177/2045125313507739.