Caution for Ketamine use in treating Depression ...and other off label uses

Treating Depression | With increasing off-label use of ketamine in patients with severe depression and other psychiatric disorders,

an expert group of the American Psychiatric Association (APA) has published a consensus statement to help guide safe and appropriate use of the anesthetic.
A growing body of research shows that ketamine can produce rapid and robust antidepressant effects in patients with treatment-resistant mood and anxiety disorders, Dr. Gerard Sanacora of Yale University School of Medicine in New Haven, Connecticut, and colleagues note in their report, online in JAMA Psychiatry.

“Despite the relatively small sample sizes, lack of longer-term data on efficacy, and limited data on safety provided by these studies,” this has led to an uptick in use of ketamine as an off-label treatment for mood and other psychiatric disorders, they point out,

“While ketamine may be beneficial to some patients with mood disorders, it is important to consider the limitations of the available data and the potential risk associated with the drug when considering the treatment option,” they write.

Currently, there are no clearly established indications for use of ketamine in the treatment of psychiatric disorders, but the most robust data supporting ketamine’s clinical benefit is in the setting of severe treatment-refractory major depression without psychotic features, Dr. Sanacora and colleagues say.

• Before initiating ketamine therapy, clinicians should do a thorough pre-treatment evaluation including other medical, psychological or social factors that may alter the risk-benefit ratio of the treatment and affect the patient’s capacity to provide informed consent, they advise.

Clinicians providing ketamine therapy should be prepared to manage potential cardiovascular and respiratory events should they occur and evaluate the patient for potential behavioral risks, including suicidal ideation, before discharge to home. Treating clinicians should also be able to ensure that rapid follow-up evaluations of patients’ psychiatric symptoms can be provided as needed, they further suggest.

While there is a growing number of reports examining the effects of various doses and rates of ketamine infusion, there is currently “insufficient information to allow any meaningful analysis of any specific dose or route of treatment compared with the standard dose of 0.5 mg/kg per 40 minutes IV,” the group says.

• They “strongly” advise against prescribing ketamine for at-home self-administration. “It remains prudent to have all doses administered with medical supervision until more safety information obtained under controlled situations can be collected,” they say, adding that the data on repeated infusions of ketamine remain limited.

“To help best ensure patient safety and to minimize risks, it is strongly advised that site-specific standard operating procedures be developed and followed for the delivery of ketamine treatments for major depressive episodes,” the authors recommend.

Summing up, Dr. Sanacora and colleagues say, “The rapid onset of robust, transient antidepressant effects associated with ketamine infusions has generated much excitement and hope for patients with refractory mood disorders and the clinicians who treat them. However, it is necessary to recognize the major gaps that remain in our knowledge about the longer-term efficacy and safety of ketamine infusions. Future research is needed to address these unanswered questions and concerns.”

The co-authors of an invited commentary say there is “little doubt that ketamine is having a major effect on psychiatry” and this “much-needed” consensus will help guide its clinical use.

“The consensus statement by Sanacora and colleagues, however, provides a sobering cautionary guide, especially as we move toward attempting to sustain the gains achieved by acute doses of ketamine. This consensus statement will not be the final word on this topic, and similar considerations will be needed for other novel treatments,” write Dr. Charles Zorumski and Dr. Charles Conway of Washington University School of Medicine in St. Louis, Missouri.

The consensus authors also “highlight the importance of enrolling patients in systematic studies to advance the field, rather than simply using ketamine in open and uncontrolled ways.

• We strongly endorse the authors’ call for a registry of patients treated with ketamine to allow coordinated data collection and to provide a monitor about ketamine use,” Drs. Zorumski and Conway say.

Note: Several consensus authors disclosed financial relationships with various pharmaceutical companies.

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