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Open Access Highly Accessed Review

Neuroinflammation and psychiatric illness

Souhel Najjar*, Daniel M Pearlman, Kenneth Alper, Amanda Najjar and Orrin Devinsky

Journal of Neuroinflammation 2013, 10:43  doi:10.1186/1742-2094-10-43

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Anti-inflammatory compounds, such as ketamine and palmitoylethanolamide as antidepressants

jan keppel hesselink   (2013-07-29 15:15)  institute neuropathic pain email

New therapies based on new ideas concerning the pathogenesis of a number of psychiatric disorders are highly needed. This article therefore is quite important to provoke original lines of thinking and to outline new research paths.

Ketamine, in this thought provoking article, correctly has been pointed out to have anti-depressant activity. Ketamine also has a number of anti-inflammatory effects not mentioned by the authors, which further supports its use in psychiatric disorders, in so far as neuro-inflammation plays a role.

Clinically relevant concentration of ketamine can inhibit TNF-alpha and IL-6 gene expressions in an in vitro model for inflammation (Toxicol Appl Pharmacol. 2008 Apr 1;228(1):105-13).

Intraoperative administration of ketamine also significantly inhibits proinflammatory cytokines, such as the early postoperative IL-6 inflammatory response (Anesth Analg. 2012 Oct;115(4):934-43)

Ketamine also inhibits on LPS-induced astrocytes activation (Cell Physiol Biochem. 2012;30(3):609-17). Overactive glia plays a well known role in chronic pain. In addition to this role glia activation can be found in stress and anxiety (Brain Behav Immun. 2013 Mar;29:136-46), as well as in bipolar disorders.

Based on ketamine's anti-inflammatory actions we use succesfully ketamine as a topical compounded 10% cream in CRPS type 1, a distinct neuro-inflammatory disorder (J Pain Res. 2013 Mar 21;6:239-45). This cream has been used in addition to oral use of palmitoylethanolamide (PEA), a endogenous anti-inflammatory agent, available as a nutraceutical (The Open Pain Journal, 2012, 5, 12-23)

PEA also proved to have anti-depressant efficacy in the classical rat forced swimming model (Pharmacol Rep. 2011;63(3):834-9). In a recent paper using a number of animal anxiety and depression models PEA showed clear anxiolytic effects (CNS Neurol Disord Drug Targets. 2013 Jul 10).

The idea that a number of psychiatric disorders might have a neuro-inflammatory pathogenesis is quite important, as it might open the door for new treatment modalities, such as ketamine and palmitoylethanolamide, perhaps as adjuncts to classical anti-depressants, This is of great importance, since the efficacy of antidepressants since the 80s of last century has not been increased compared to the gold standard antidepressant drugs such as amitriptyline, despite many thousands of clinical trials.

The same holds trough for anti-psychotic drugs, were haloperidol and clozapine remain the gold standards.

If we start looking into the pharmacological profiles of drugs useful to treat psychiatric disorders, neuro-inflammation inhibitors might become a new generation of treatments for such disorders.

Competing interests

None declared

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