In the Journals

Researchers offer consensus on ketamine for mood disorders

A recent consensus statement in JAMA Psychiatry reviewed available research on the use of ketamine for psychiatric indications and provided recommendations for clinicians considering or currently administering ketamine.

“Reports of ketamine’s unique antidepressant effects, combined with frequent media coverage promulgating the potential benefits of ketamine treatment, have generated substantial interest and optimism among patients, families, patient advocacy groups, and clinicians alike. This interest has led to a rapidly escalating demand for clinical access to ketamine treatment and an increasing number of clinicians willing to provide it,” Gerard Sanacora, MD, PhD, of Yale University School of Medicine, and colleagues wrote. “However, many in the field suggest that caution should be used with this approach, as the numbers of patients included in these published studies and case series remain relatively small, and ketamine treatment for mood disorders has not been tested in larger-scale clinical trials to demonstrate its durability and safety over time.”

Further, ketamine has yet to undergo FDA review or approval for treatment of mood disorders and there are no published guidelines or recommendations for clinician training requirements to be completed before administering ketamine.

To provide a consensus on the use of ketamine for mood disorders, researchers reviewed current research.

The strongest data available supported the use of ketamine for treatment of major depressive episodes without psychotic features associated with major depressive disorder. However, these data are limited because most studies only evaluated efficacy during the first week following a single ketamine infusion, according to researchers.

Although a dosage of 0.5 mg/mg per 40 minutes IV has “proven to be relatively safe to date,” some acute effects on cardiovascular function and behavior have been noted.

Therefore, researchers suggested that a facility in which ketamine is used to treat mood disorders should have the means to monitor basic cardiovascular and respiratory function.

Regarding administration procedures, researchers found limited data on the use of different delivery routes and doses of ketamine.

They recommended a standard pre-dosing procedure include informed consent, baseline vital signs assessment of blood pressure, heart rate and oxygen saturation or end-tidal CO2, criteria for acceptable baseline vital signs before medication initiation, and a “time-out” procedure that confirms name of patient and correct dosing parameters.

Standard operating procedures should also include ongoing assessments of physiological and psychological status during the infusion process, according to researchers.

Findings from follow-up assessments on benefits of repeated ketamine infusions and efficacy of long-term repeated administration are limited.

The researchers advised clinicians to be vigilant of the known potential for abuse of ketamine and to employ close clinical follow-up with intermittent urine toxicology to ensure abuse does not develop.

“Although economic factors make it unlikely that large-scale, pivotal phase 3 clinical trials of racemic ketamine will ever be completed, there are several studies with federal and private foundation funding aiming to address some of these issues,” the researchers wrote. “It is imperative that clinicians and patients continue to consider enrollment in these studies when contemplating ketamine treatment of a mood disorder. It is only through these standardized clinical trials that we will be able to collect the data necessary to answer some of the crucial questions pertaining to the efficacy and safety of the drug.”

In addition, the researchers suggested developing a coordinated system of data collection for all individuals receiving ketamine for mood disorders to add to the knowledge base. – by Amanda Oldt

Disclosure: Sanacora reports receiving consulting fees from Allergan, Alkermes, AstraZeneca, BioHaven Pharmaceuticals, Hoffman La-Roche, Johnson & Johnson (Janssen), Merck, Naurex, Servier Pharmaceuticals, Taisho Pharmaceuticals, Teva, and Vistagen Therapeutics; receiving research contracts from AstraZeneca, Bristol-Myers Squibb, Eli Lilly & Co, Johnson & Johnson (Janssen), Hoffman La-Roche, Merck & Co, Naurex, and Servier; free medication for a NIH-sponsored study by Sanofi; holding shares in BioHaven Pharmaceuticals Holding Company; and being a co-inventor on patent No. 8778979. Please see the study for a full list of relevant financial disclosures.

A recent consensus statement in JAMA Psychiatry reviewed available research on the use of ketamine for psychiatric indications and provided recommendations for clinicians considering or currently administering ketamine.

“Reports of ketamine’s unique antidepressant effects, combined with frequent media coverage promulgating the potential benefits of ketamine treatment, have generated substantial interest and optimism among patients, families, patient advocacy groups, and clinicians alike. This interest has led to a rapidly escalating demand for clinical access to ketamine treatment and an increasing number of clinicians willing to provide it,” Gerard Sanacora, MD, PhD, of Yale University School of Medicine, and colleagues wrote. “However, many in the field suggest that caution should be used with this approach, as the numbers of patients included in these published studies and case series remain relatively small, and ketamine treatment for mood disorders has not been tested in larger-scale clinical trials to demonstrate its durability and safety over time.”

Further, ketamine has yet to undergo FDA review or approval for treatment of mood disorders and there are no published guidelines or recommendations for clinician training requirements to be completed before administering ketamine.

To provide a consensus on the use of ketamine for mood disorders, researchers reviewed current research.

The strongest data available supported the use of ketamine for treatment of major depressive episodes without psychotic features associated with major depressive disorder. However, these data are limited because most studies only evaluated efficacy during the first week following a single ketamine infusion, according to researchers.

Although a dosage of 0.5 mg/mg per 40 minutes IV has “proven to be relatively safe to date,” some acute effects on cardiovascular function and behavior have been noted.

Therefore, researchers suggested that a facility in which ketamine is used to treat mood disorders should have the means to monitor basic cardiovascular and respiratory function.

Regarding administration procedures, researchers found limited data on the use of different delivery routes and doses of ketamine.

They recommended a standard pre-dosing procedure include informed consent, baseline vital signs assessment of blood pressure, heart rate and oxygen saturation or end-tidal CO2, criteria for acceptable baseline vital signs before medication initiation, and a “time-out” procedure that confirms name of patient and correct dosing parameters.

Standard operating procedures should also include ongoing assessments of physiological and psychological status during the infusion process, according to researchers.

Findings from follow-up assessments on benefits of repeated ketamine infusions and efficacy of long-term repeated administration are limited.

The researchers advised clinicians to be vigilant of the known potential for abuse of ketamine and to employ close clinical follow-up with intermittent urine toxicology to ensure abuse does not develop.

“Although economic factors make it unlikely that large-scale, pivotal phase 3 clinical trials of racemic ketamine will ever be completed, there are several studies with federal and private foundation funding aiming to address some of these issues,” the researchers wrote. “It is imperative that clinicians and patients continue to consider enrollment in these studies when contemplating ketamine treatment of a mood disorder. It is only through these standardized clinical trials that we will be able to collect the data necessary to answer some of the crucial questions pertaining to the efficacy and safety of the drug.”

In addition, the researchers suggested developing a coordinated system of data collection for all individuals receiving ketamine for mood disorders to add to the knowledge base. – by Amanda Oldt

Disclosure: Sanacora reports receiving consulting fees from Allergan, Alkermes, AstraZeneca, BioHaven Pharmaceuticals, Hoffman La-Roche, Johnson & Johnson (Janssen), Merck, Naurex, Servier Pharmaceuticals, Taisho Pharmaceuticals, Teva, and Vistagen Therapeutics; receiving research contracts from AstraZeneca, Bristol-Myers Squibb, Eli Lilly & Co, Johnson & Johnson (Janssen), Hoffman La-Roche, Merck & Co, Naurex, and Servier; free medication for a NIH-sponsored study by Sanofi; holding shares in BioHaven Pharmaceuticals Holding Company; and being a co-inventor on patent No. 8778979. Please see the study for a full list of relevant financial disclosures.