An expert consensus statement aimed at helping physicians safely and appropriately administer the anesthetic ketamine (Ketalar, Par Sterile Products) for the treatment of severe depression and other mood disorders has been issued, at least in part in response to the growing and ungoverned off-label use of the drug by ketamine clinics throughout the United States.
"There is clear evidence that the use of ketamine for the treatment of mood disorders is increasing rapidly around the country, and there was a need for some guidance around what we know so, at a minimum, there will be some information out there for clinicians who are interested in either referring people or using the treatment themselves," the statement's lead author, Gerard Sanacora, MD, PhD, professor of psychiatry and director of the Yale Depression Research Program, New Haven, Connecticut, told Medscape Medical News.
"The reality is that this is a unique situation where we have a tremendously promising treatment. We use it a lot, and I believe this really is a transformative change in the field, but we do have to appreciate the limits of the knowledge that we are working with right now," he added.
The consensus statement was published online March 1 in JAMA Psychiatry.
The most robust evidence supporting the use of ketamine in psychiatric disorders is in the treatment of major depressive episodes in the absence of psychiatric features.
"Even these data are limited by the fact that most of those studies evaluated efficacy only during the first week following a single infusion of ketamine," the authors caution.
The authors state that physicians may consider the use of ketamine provided they conduct a comprehensive evaluation to confirm that the patient meets the appropriate diagnostic criteria for depression, that they ensure that the patient has undergone an adequate trial of other US Food and Drug Administration–approved antidepressant therapies, and that they rule out any history of substance abuse or psychotic disorders.
Expert committee members also "strongly encourage" physicians to obtain a baseline urine toxicology screen to ensure the patient-reported substance use history is accurate.
Written informed consent should also be obtained for each ketamine candidate. In addition, physicians need to discuss the potential risks associated with ketamine use and the limits of information supporting its benefits with all patients deemed to be appropriate candidates for ketamine treatment.
"What we did was summarize the current literature so everybody would know what it is and then make our best guess as to what the minimal requirements are to use the drug," Charles Nemeroff, MD, professor and chairman, Department of Psychiatry and Behavioral Sciences, Leonard M. Miller School of Medicine, University of Miami, Florida, told Medscape Medical News.
Dr Nemeroff is also a member of the consensus writing committee as well as the American Psychiatric Association Council of Research Task Force on Novel Biomarkers and Treatments that asked experts to prepare recommendations on ketamine use based on available evidence.
Blood pressure can spike in response to a ketamine infusion in some patients. Although data suggest that ketamine seems to be relatively safe at a standard intravenous dose of 0.5 mg/kg per 40 min, "patients should be in a facility where you can monitor blood pressure and there's a physician present who is trained to deal with a medical catastrophe should one occur," said Dr Nemeroff.
Committee members also caution that some patients may experience transient dissociative or psychotomimetic effects in response to ketamine infusion. Physicians also need to be prepared to treat emergency behavioral problems should they arise.
Physicians should also be capable of evaluating patients for the presence of suicidal ideation prior to discharging patients home. Adequate follow-up and a long-term plan to manage the patient's depression are mandatory.
The consensus authors also strongly advise physicians to adopt a standard operating procedure for the delivery of ketamine treatments. Such a procedure should include at minimum the following:
Confirmation of the preprocedural evaluation and informed consent
Baseline assessment of vital signs (blood pressure, heart rate, oxygen saturation or end-tidal CO2)
Incorporation of a "time-out" interlude during which the name of the patient and correct dosing parameters are confirmed
Ongoing assessment of the patient's physiologic and mental status during the infusion process
Experts also caution that the benefits of giving repeated infusions of ketamine are as yet poorly defined.
Small case series suggest that ketamine can be given more than once, but to date, most studies have investigated the effects of treatment of less than 1 month's duration.
Probably the best evidence to date suggests that giving the drug twice a week for up to 4 weeks is efficacious, but the authors caution that patients still need to be monitored closely using a rating instrument to objectively assess any change in the patient's mood and that the physician reevaluate the risk of continuing treatment against potential benefit.
Experts also strongly recommend that the benefit of each ketamine infusion be weighed against the potential risks associated with long-term exposure to the drug. They note that the paucity of information on the long-term use of ketamine is one of the major drawbacks to its use.
Given its potential for abuse, "clinicians should be vigilant about assessing the potential for patients to develop ketamine use disorder," they write, "[and] the number and frequency of treatments should be limited to the minimum necessary to achieve clinical response."
Experts also recommend that ketamine be discontinued if dosing cannot be tapered to a minimum of one dose per week by the second month of treatment, the goal being to eventually discontinue treatment altogether.
"A really important part of these recommendations is to make sure people fully understand what the risks and benefits are to treatment so that they are able to make an informed decision based on knowing what the risk-benefit ratio is," Dr Sanacora noted.
"My personal view is that ketamine is an incredibly promising treatment, but we do have some concerns about its use, and if ketamine is going to be offered, it should be done in a way that provides the highest level of safety available," Dr Sanacora said.
Dr Nemeroff agreed, adding that he is not at all opposed to the use of ketamine for treatment-resistant depression but that he would like practitioners to proceed with caution if they do decide to offer it.
"This is the number one drug of abuse in Asia, so I think one has to be thoughtful about who you are going to prescribe it to and ask important questions, such as, 'Have patients been adequately treated with other approved treatments? Have they been screened for substance and alcohol abuse?' " he said.
"So while I think ketamine is very exciting and that we should follow up on it, we need a better database, because the one we have now is inadequate."
The original article contains a full listing of the authors' financial relationships with industry.
JAMA Psychiatry. Published online March 1, 2017. Abstract
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Cite this: New Guidance on Ketamine for Mood Disorders - Medscape - Mar 02, 2017.