Ketamine for Depression: A Perspective from the US

Ketamine evokes rapid and robust antidepressant effects, according to doctors

A new consensus statement reviews preliminary evidence that the dissociative anesthetic ketamine (Ketalar, JHP Pharmaceuticals) can evoke "rapid and robust" antidepressant effects in patients with mood and anxiety disorders who were previously resistant to treatment, and offers considerations to facilitate appropriate patient selection and safe medication administration.


The consensus statement was developed by the American Psychiatric Association () Council of Research Task Force on Novel Biomarkers and Treatments. Lead author, Gerard Sanacora, MD, PhD, Yale University School of Medicine (pictured), and colleagues on the Task Force note that reports of the unique drug effect combined with frequent media coverage has generated a substantial demand for treatment access without the availability of usage guidelines or scrutiny by the FDA.

"The relatively unique nature of this situation presents an urgent need for some guidance on the issues surrounding the use of ketamine treatment in mood disorders," Sanacora and colleagues indicate.

In accompanying commentary, Charles Zorumski, MD and Charles Conway, MD, Center for Brain Research in Mood Disorders, Department of Psychiatry, Washington University School of Medicine, St Louis, Missouri, opined, "There is little doubt that ketamine is having a major effect on psychiatry.

"If clinical studies continue to support the antidepressant efficacy of ketamine," Zorumski and Conway added, "psychiatry could enter an era in which drug infusions and deliveries with more rapid responses become common."

Anticipating that possibility, the consensus statement recommends development of clinical credentialing for ketamine administration for the treatment of mood disorders. Clinicians should be prepared, the statement indicates, to manage cardiovascular events, as well as emergency behavioral situations, including suicidal ideation.

Treatment settings should have the means for monitoring basic cardiovascular and respiratory function, and to rapidly address and stabilize a patient if the need presents, the statement recommends. Standard operating procedures should include ongoing assessment of the physiological and mental status during infusion, including respiration and cardiovascular function, and the level of consciousness. The statement also recommends that these procedures delineate criteria for stopping the infusion, and include a plan for managing treatment-emergent events.

Patient selection for the treatment should follow from careful consideration of the risks and benefits, according to the statement, within the context of the severity of depression, duration of current episode, treatment history and urgency for treatment. In addition, there should be an assessment of other medical, psychological or social factors that could alter the risk to benefit ratio or affect the capacity to provide informed consent.

The consensus statement indicates there are insufficient data to recommend dosage variance, except for high body mass index, from the most commonly used dosage of 0.5mg/kg by intravenous infusion over 40 minutes. Although a few case series have tested repeated administrations to extend therapeutic drug effect, which can recede within a week after a single administration, the statement notes that effects from long-term exposure are unknown.

"The scarcity of this information is one of the major drawbacks to be considered before initiating ketamine therapy for patients with mood disorders and should be discussed with the patient before beginning treatment," Sanacora and colleagues indicate.


The consensus statement by the Council of Research Task Force on Novel Biomarkers and Treatments was published in the April issue of JAMA Psychiatry. A Consensus Statement on the Use of Ketamine in the Treatment of Mood Disorders.