History of Psychosis May Not Exclude Ketamine for Depression

Megan Brooks

February 09, 2017

Preliminary evidence from two case reports suggests that a history of psychosis should not exclude a patient with severe depression from receiving ketamine in a clinical setting, researchers say.

"There are some real concerns about whether ketamine should be used in people with psychotic disorders, based mainly on early studies suggesting that some of the immediate effects of ketamine can actually mimic some of the symptoms of psychosis," Gerard Sanacora, MD, PhD, professor of psychiatry, Yale University, New Haven, Connecticut, noted in an interview with Medscape Medical News.

Recently, however, there have been a few reports in the literature demonstrating that ketamine can be used safely and effectively in patients with severe depression and psychotic features.

In a report published online January 23 in Biological Psychiatry, Dr Sanacora and colleagues describe "encouraging" long-term results in two patients with psychotic symptoms complicating severe depressive episodes who have been maintained on monthly infusions of ketamine.

In these two patients, "we saw an antidepressant effect but not any worsening of perceptual or cognitive effects that could be related to psychosis," said Dr Sanacora.

One patient was a 52-year-old woman with a long history of unipolar depression and psychotic features who presented with depressive symptoms, auditory hallucinations, and paranoid delusions and who reported considering suicide.

A lack of response to multiple and varied medications led to an initial trial of ketamine (0.5 mg/kg continuous infusion over 40 min).

During the infusion, the patient reported mild dissociative symptoms, fatigue, and a mild headache. After the infusion, the patient experienced dramatic improvement in her mood, and her auditory hallucinations and paranoia ceased. During the course of the treatment, Hamilton Depression Rating Scale (HAM-D) scores were reduced from 19 to 9, the researchers report.

The patient subsequently received 12 ketamine infusions over the course of 1 year. She missed treatment for 2 months, owing to a hip arthroplasty, which lead to relapse, but she recovered quickly after receiving two treatments within a 1-week interval. The patient is now maintained on monthly treatments of ketamine. Her Quick Inventory of Depressive Symptomatology (QIDS) score at the start of ketamine treatment was 36 and has decreased to 6.

The other patient was a 55-year-old woman with a long and severe history of schizoaffective disorder who presented with depressive symptoms and severe suicidal ideation. The patient was withdrawn, whispering, catatonic, and responding to internal stimuli. She had a history of self-harm, medication overdoses, and a violent psychotic episode in which she set her home on fire in response to command hallucinations.

The decision was made to try ketamine infusion (0.5 mg/kg over 40 min), the researchers say, owing to the severity of past depressive episodes and the fact that the patient had previously been given ketamine as the anesthetic agent in conjunction with electroconvulsive therapy (ECT), which had a strong antidepressant effect, although no seizure was induced.

After the initial infusion, the patienet's mood improved dramatically, and she was free of psychotic symptoms, report the researchers. After receiving five ketamine infusions over time, her medication was adjusted, and the patient was discharged without suicidal ideations and with significantly improved mood. HAM-D scores went from 29 to 8 during the course of treatment.

This patient has remained stable with monthly ketamine infusions for a period of 1 year. Her QIDS score has also dropped dramatically since starting treatment.

Cautionary Notes

"Ketamine in general is being used quite a bit in the open-label setting for antidepressant effects. There are an increasing number of centers and clinicians around the country that are beginning to offer it," Dr Sanacora told Medscape Medical News. It is now "fairly well established" that ketamine causes a transient antidepressant response in about 50% to 70% of patients, he noted.

Far less is known about ketamine's use in the setting of psychotic symptoms. The data on repeated long-term ketamine use in these two patients with psychotic features complicating severe depression are "reassuring to the field," write Dr Sanacora and colleagues. Both patients treated with ketamine have had long-term improvement in depression, and the agent has not induced psychotic symptoms.

Nevertheless, until more data are gathered, Dr Sanacora urged caution in using ketamine in the setting of psychotic symptoms.

"It's not out of the question" to try ketamine in a patient with psychotic features "as long as there is safety criteria built in from the very beginning," he told Medscape Medical News. "It really should only be used after more established treatments, including an atypical antipsychotic, or even probably ECT.

"The population with major depression and psychotic features is a very difficult population to treat," he added, "and if ketamine could have some benefit, that would be a very helpful."

Dr Sanacora has relationships with several pharmaceutical companies, including Alkermes, AstraZeneca, BioHaven Pharmaceuticals, and Naurex. The original article contains a complete list of such relationships.

Biol Psychiatry. Published online January 23, 2017. Abstract


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