Delusions are defined as fixed false beliefs that are not within normal parameters of society, culture, or religion that can be part of psychotic or mood disorders. They can be difficult to treat and, for some inpatient individuals, persistent delusions can make safe discharge impossible. Ketamine is a dissociative agent that has shown promise in treating mood disorders. Despite this, clinicians hesitate to prescribe this when a patient presents with any type of psychotic symptom. There is proof that ketamine is safe to use with psychotic symptoms, and there is growing evidence that it may be a suitable treatment alternative for delusions resistant to other psychopharmacology.

A literature review using articles from multiple databases was conducted to gather supporting evidence on the use of ketamine in the context of psychosis. Since there has not been a reported conducted study specifically for ketamine and delusions, a look into its use for psychosis was done to find links between the neurobiology of delusions and the mechanism of action of ketamine.

Current literature does not demonstrate that ketamine within a therapeutic setting exacerbates psychotic symptoms in those with depression or bipolar disorder, regardless of the presence of psychotic features, nor does it reveal that predisposed patients experience lasting psychotic effects. Furthermore, although ketamine is often used to model schizophrenia, brain connectivity seen during ketamine-induced delusions is opposite to the connectivity seen in delusions in the context of chronic schizophrenia. Regardless of connectivity patterns, ketamine appears to act upon many of the same mechanisms that underlie delusions. There is evidence delusions are characterized by low belief flexibility, high prediction error, and high aberrant salience. An animal model of stress-induced cognitive dysfunction found that ketamine corrected the cognitive flexibility deficits. Ketamine has been shown to alter prediction error in those suffering from major depressive disorder, resulting in greater optimism bias when patients update maladaptive beliefs post-ketamine administration. In respect to aberrant salience, neural networks affecting this include midbrain dopaminergic neurons and their projections to striatal and frontal cortical regions. Studies have shown this effect was reduced by ketamine-induced plasticity in the orbitofrontal cortex.

Psychotic symptoms may not be an absolute contraindication for ketamine treatment. In fact, ketamine could be beneficial in the treatment of various mental illnesses with psychotic features that are not amenable to classical treatment. The dissociative properties may jump-start treatment while waiting for antipsychotics to work. This could significantly reduce hospital stays, especially for patients in long-term facilities.

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