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LogoKeyPointsBox.pngThe combination of jaundice and cystitis in a young patient should make you think of chronic ketamine abuse

Has analgesic properties as well as being an intravenous anaesthetic agent with very little risk of respiratory depression. Not used much in adults in the UK, although a commonly used anaesthetic agent in developing countries and in onsite emergency trauma treatment. It produces a dissociated state where the patient can still respond. Can be useful in the paediatric population as the airway reflexes are said to be less suppressed.

It is psycho-active leading to both recreational use (which runs the risk of inducing a severe cystitis) and attempts to use it as a rapidly acting agent in refractory depression[1][2][3]. Individual response in this last indication shows marked variability and may be related to differential metabolism between individuals[4]. The best evidence is for the dose 0.5mg/kg intravenously.[5]

Clinical Use


  • Anaesthesia - induction and maintenance


In clinical use it is usually given intravenously, but in 'recreational use' is often taken orally.

Clinical Issues


Cautions and Interactions

Side effects

  • Hypersalivation (sometimes co-administered with anti-cholinergics, typically anti-muscarinics such as atropine).
  • Muscle movements
  • Tachycardia
  • Hypertension
  • Hallucinations
  • Nightmares
  • Bladder symptoms with chronic use including ulcerative‎ cystitis[6]
  • Hepatic derangement on chronic use

Special advice

  • Abuse potential
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It has been reclassified from Class C to Class B under the Misuse of Drugs Act 1971


The drug is a racemic mixture. It blocks glutamatergic NMDA receptors.(S)-ketamine has a threefold higher affinity for the NMDA receptor than (R)-ketamine)[7]. There is upregulation of α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) subtypes with intracellular changes in protein expression, including the proteins mammalian target of rapamycin (mTOR) and brain-derived neurotrophic factor (BDNF). It actually interacts at multiple sites in the central nervous system, including NMDA and non-NMDA glutamate receptors, nicotinic and muscarinic cholinergic receptors, and adrenergic and opioid receptors( μ- and δ-opioid receptors but not κ-opioid receptors)[8].


  1. Diazgranados N, Ibrahim L, Brutsche NE, Newberg A, Kronstein P, Khalife S, Kammerer WA, Quezado Z, Luckenbaugh DA, Salvadore G, Machado-Vieira R, Manji HK, Zarate CA. A randomized add-on trial of an N-methyl-D-aspartate antagonist in treatment-resistant bipolar depression. Archives of general psychiatry. 2010 Aug; 67(8):793-802.(Link to article – subscription may be required.)
  2. Zarate CA, Brutsche NE, Ibrahim L, Franco-Chaves J, Diazgranados N, Cravchik A, Selter J, Marquardt CA, Liberty V, Luckenbaugh DA. Replication of ketamine's antidepressant efficacy in bipolar depression: a randomized controlled add-on trial. Biological psychiatry. 2012 Jun 1; 71(11):939-46.(Link to article – subscription may be required.)
  3. Caddy C, Giaroli G, White TP, Shergill SS, Tracy DK. Ketamine as the prototype glutamatergic antidepressant: pharmacodynamic actions, and a systematic review and meta-analysis of efficacy. Therapeutic advances in psychopharmacology. 2014 Apr; 4(2):75-99.(Link to article – subscription may be required.)
  4. Villaseñor A, Ramamoorthy A, Silva Dos Santos M, Lorenzo MP, Laje G, Zarate C, Barbas C, Wainer IW. A pilot study of plasma metabolomic patterns from patients treated with ketamine for bipolar depression: evidence for a response-related difference in mitochondrial networks. British journal of pharmacology. 2014 Apr; 171(8):2230-42.(Link to article – subscription may be required.)
  5. Xu Y, Hackett M, Carter G, Loo C, Gálvez V, Glozier N, Glue P, Lapidus K, McGirr A, Somogyi AA, Mitchell PB, Rodgers A. Effects of Low-Dose and Very Low-Dose Ketamine among Patients with Major Depression: a Systematic Review and Meta-Analysis. The international journal of neuropsychopharmacology / official scientific journal of the Collegium Internationale Neuropsychopharmacologicum (CINP). 2015 Nov 17.(Epub ahead of print) (Link to article – subscription may be required.)
  6. Peng TR, Lee MC, Wu TW, Lan CC. Suspected ketamine-associated lower urinary tract symptoms. Urology journal. 2014 Mar-Apr; 11(2):1508-10.(Epub)
  7. Höffken O, Haussleiter IS, Westermann A, Lötsch J, Maier C, Tegenthoff M, Schwenkreis P. Influence of (S)-ketamine on human motor cortex excitability. Experimental brain research. 2013 Mar; 225(1):47-53.(Link to article – subscription may be required.)
  8. Pacheco DD, Romero TR, Duarte ID. Central antinociception induced by ketamine is mediated by endogenous opioids and μ- and δ-opioid receptors. Brain research. 2014 Mar 24.(Epub ahead of print) (Link to article – subscription may be required.)
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