Ketamine is a substance with general anesthetic action, derived from phencyclidine (with action in about 30-45 minutes and with fewer side effects), which causes dissociative anesthesia , with some important uses in the medical field. In fact, ketamine is used in anesthesia, obstetrics, pediatric analgesia and also in the veterinary field. Ketamine (like memantine and riluzole) is a substance that acts on the glutamma system and has an antagonistic action of glutamergic NMDA receptors. It also acts on the catecholaminergic and cholinergic brain neurotransmission pathways. The effects of ketamine are dependent on the dosage used, the route of intake used and other pharmacokinetic and pharmaceutical parameters. In particular, Ketamine would cause dissociative anesthesia, through a depression of the thalamo-cortical system and an activation of the limbic system. At low, sub-anesthetic dosages, ketamine causes strong visual-auditory hallucinations and dissociative experiences defined as Near Death Experiences or mind-body dissociation. At high dosages it determines an anesthetic effect (from the technical data sheet the average dose necessary to obtain 5-10 minutes of surgical anesthesia and 2 mg / kg).
Ketamine is used as a substance of abuse and is known by various names such as “Special K”, “K”, “Valium for cat”, is inserted for its dissociative and euphoric action within hallucinogenic substances. The substance produces psychedelic effects of detachment from the body, ranging from “near-death” hallucinations to real states of mind-body dissociation, and other physical symptoms (represented by an increased activity of the sympathetic system).
In the medical-psychiatric field , it seems that ketamine and other drugs active on the glutamma system may play a role in the improvement of depressive symptoms .. In particular ketamine, memantine (NMDA receptor antagonists), and riluzole (another substance active on the glutamma system), could play an important role in the treatment of bipolar and unipolar depression. In fact, the intravenous administration of a single infusion of ketamine seems to be capable of inducing a rapid and robust antidepressant action (within minutes) (Diazgranados N et al., 2010). Riluzole has been shown to be useful in treatment-resistant unipolar depression in two open-label studies (Mathew SJ et al., 2008). Memantine in augmentation has been shown to have an antimanic and mood stabilizing effect with an excellent safety and tolerability profile (Anand A and coll., 2012; Koukopoulos A and coll., 2012).But what would these drugs add compared to previous antidepressants? The importance of drugs active on the glutamergic system would consist in the fact that the blocking of NMDA receptors could prevent and suppress mania (Koukopoulos A et al., 2010), while for the other classical antidepressants the antidepressant action induces mania and rapid cycling through the sensitization of dopaminergic D2 receptors (sensitization linked to the stimulation of NMDA receptors).
In conclusionketamine is a substance that can be used in the medical field, at the discretion of the specialist, and only when there are clear clinical indications (in the near future the indication for forms of depression resistant to drug treatment for ketamine will probably become available) .
For bibliographic references:
- 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 Jr. A randomized add-on trial of an N-methyl-D-aspartate antagonist in treatment-resistant bipolar depresion. Arch Gen Psychiatry. 2010 Aug;67(8):793-802.
- Koukopoulos A, Reginaldi D, Serra G, Koukopoulos A, Sani G, Serra G. Antimanic and mood-stabilizing effect of memantine as an augmenting agent in treatment-resistant bipolar disorder. Bipolar Disord. 2010 May;12(3):348-9.
- Papolos DF, Teicher MH, Faedda GL, Murphy P, Mattis S. Clinical experience using intranasal ketamine in the treatment of pediatric bipolar disorder/fear of harm phenotype. J Affect Disord 2013; 147(1-3):431-6.
- Post RM. Promising avenues of therapeutics for bipolar illness. Dialogues Clin Neurosci. 2008;10(2):193-201.
- Sienaert P, Lambrichts L, Dols A, De Fruyt J. Evidence-based treatment strategies for treatment-resistant bipolar depression: a systematic review.Bipolar Disord. 2013 Feb;15(1):61-9.
