The role of Ketamine in treatment-resistant Obsessive Compulsive Disorder

Federico Motta
Università degli Studi di Milano-Bicocca


Obsessive-compulsive disorder (OCD) is a relatively common and frequently debilitating neuropsychiatric disorder that affects approximately 1–3% of the general population, it is characterized by recurrent persistent thoughts (obsessions) and repetitive compulsory behaviours (compulsions).
Ketamine, an antagonist of NMDA receptor, is a glutamatergic modulator and its s-enantiomer Esketamine has been used and approved by the FDA and EMA for treatment-resistant depression (TRD). Over the last decade, the role of Ketamine has been investigated both in animals and humans and the aim of this current brief review is to expose the encouraging findings on the use of Ketamine in OCD.

The papers were selected among PubMed, SCOPUS and Google Scholar with key words as: “Ketamine”,“OCD”, “obsessive compulsive disorder”, “obsessions”, “compulsions”, “mice”, from 2010 to 2020. Most of the studies on animal models tried to mirror OCD symptoms and phenotypes with different models: genetic, pharmacology and behavioural.
In the study performed by Cristiana Luz Tosta et al, the animal disease model showed that mice treated with a single systemic administration of S-ketamine reverted the behavioural animal model; displacing a significant decrease of objects buried which are considered to mime OCD repetitive thoughts and compulsions.
Currently, there are few human studies focused on the effect of ketamine infusion on OCD severity assessed by specific psychiatric scales, mostly Yale-Brown Obsessive Compulsive Scale (Y-BOCS) and Obsessive Compulsive Visual Analogue Scale (OCD-VAS) and Clinical Global Impression Scale (CGI).
In the first human trial performed by Bloch et al, an infusion of ketamine was administered in 10 subjects with treatment-resistant OCD and it showed to be effective in reducing Y-BOCS, OCD-VAS, CGI scores after one hour from the infusion but it did not seem to persist after the dissipation of the acute effects.
The second study performed by Rodriquez et al, included 15 participants in a double-blind and randomized trial. The clinical improvement was assessed with YBOCS and OCD-VAS during each infusion and daily for one week.
The results highlighted that the group treated with Ketamine showed a reduction of both OCD-behaviours and scales scores right after the administration and, in contrast with the first study, persistently for one week. The control group received saline solution and it did not show any variation in the scales scores.
In general, the use of Ketamine showed a rapid and significant decrease of animal model related tasks and of OCD symptoms in humans.
Since the results are promising, the application of Ketamine in resistant-OCD needs to be further investigated by new approaches (i.e. hIPCs disease modelling and other animal modelling disease) to fully understand the mechanisms of action. Moreover, other human trials should be performed with larger samples of patients, repetitive administrations and long-term observation.

1- Cristiana Luz Tosta, et al. S-ketamine reduces marble burying behaviour: Involvement of ventromedial orbitofrontal cortex and AMPA receptors. Neuropharmacology, 2019
2- Michael H. Bloch et al, Effects of Ketamine in Treatment-Refractory Obsessive-Compulsive Disorder. Biol Psychiatry, 2012
3- Rodriquez et al, Randomized Controlled Crossover Trial of Ketamine in Obsessive-Compulsive Disorder: Proof-of-Concept. Neuropsychopharmacology, 2013

The role of Ketamine intreatment-resistant Obsessive-Compulsive Disorder – Federico Motta (Università degli Studi di Milano-Bicocca)