Ketamine likely does not worsen psychotic symptoms, contrary to assumption

Ketamine did not appear to worsen psychotic symptoms among predisposed patients, according to results of a systematic review published in Journal of Clinical Psychiatry.

“The potential schizophrenia-like effects of ketamine have led to exclusion of patients with depression with current or past psychotic symptoms in the majority of studies investigating the antidepressant potential of ketamine,” Jolien K. E. Veraart, MD, of the department of psychiatry at the University of Groningen in the Netherlands, and colleagues wrote. “This exclusion has important clinical implications, as psychotic symptoms are common in depressed patients (psychotic symptoms were present in a median proportion of 19% in studies including both in and outpatients or only outpatients and 42% in studies including only inpatients). Psychotic symptoms occur especially in more severe depression, which is associated with poorer treatment outcome and higher relapse rates.”

Because of the common occurrence of psychotic features among patients with treatment-resistant depression, as well as treatment-resistant depressive symptoms among patients with schizophrenia, the researchers sought to determine whether ketamine administration actually increases risk for psychosis. They searched two databases from inception to March 2020 without date or language restrictions for studies on ketamine treatment for depression or negative symptomatology among patients with a history of psychosis or current psychotic symptoms. They used the terms ketamine and psychosis, as well as psychotic or schizo, and filtered for human studies.

Veraart and colleagues included nine reports of pilot studies and care reports with 41 total patients. Study data suggested that short-term ketamine treatment for depression, as well as for negative symptoms, among patients with a history of psychosis or current psychotic features was generally safe and effective, with mild and self-limiting side effects. They observed no psychotic exacerbation among patients in the included cases, with some cases featuring improvement in or disappearance of comorbid psychotic symptoms after ketamine or esketamine administration for depression.

“These observations may serve as an important first step toward broadening the indication for ketamine treatment studies,” the researchers wrote. “Further randomized controlled trials are needed to assess the efficacy and tolerability of repeated ketamine and esketamine treatment in depressed patients with vulnerability to psychosis.”