A growing number of psychiatrists have begun to offer Ketamine, a powerful anesthetic associated with dissociative symptoms, as an off-label treatment for depression in patients who have not responded to other, more traditional treatments. (JAMA Psychiatry. March 2017). A number of small well-controlled studies have found that ketamine can relieve and even eliminate depressive states and suicidal depression in a matter of hours in these otherwise non responders. Ketamine can be administered safely, via infusion, by anesthesiologists with close monitoring in a hospital or surgical setting. Because of the potential for adverse reactions, a much needed consensus statement from the American Psychiatric Association task force offers some welcome guidance and recommendations for clinicians.

What is Ketamine?

Ketamine was developed more than 50 years ago as an anesthetic. Ketamine is a safe, effective, fast acting anesthetic with a good safety profile. It is approved for anesthesiology use on both pediatric and adult patients as well as animals. Ketamine is a dissociative anesthetic which describes its attractiveness as a drug of abuse. It was a popular club drug called “Special K” during the Rave movement and currently the number one club drug in Asia today.

Depression is a Major Public Health Problem

Considering that that up to one-third of patients with major depression fail to respond to available treatments, and many more experience only a partial response, psychiatrists and researchers have been looking for improved treatment options. SSRIs, while offering less side effects and more safety over the tricyclics, do not help everyone. Moreover, current treatment regimens have not significantly reduced suicide, disability and despair caused by depression. Remember, the mortality rate for untreated or under-treated depression among adults is over 15%. Accordingly, the need for new, novel effective treatments has never been greater. With the exception of Transcranial Magnetic Stimulation (TMS), the FDA has not approved any new treatment modalities for depression. This is why we are cautiously hopeful regarding the potential of ketamine as a bonafide treatment for major depression.

Ketamine is delivered as a low dose intravenous infusion of 0.5mg/kg over forty minutes. The results are often dramatic. However, a single infusion may last for only one week. Psychiatrists are hoping to extend the benefit by giving repeated infusions. Cognitive impairment from the acute dissociative state, as well as transient hypertension, that can be mediated with clonidine, are a concern, and the long term risks remain unknown. Still, the findings are remarkable. Small clinical studies indicate more than 70 percent of patients with treatment-resistant depression experience significant relief with ketamine infusion therapy. In addition, the fact that ketamine’s mechanism of action and efficacy may open a door to a new treatment targets as a novel and effective treatment for depression. Yet, perhaps the most exciting aspect is the nearly instantaneous response, whereas the therapeutic benefit of most current treatments can take at least three weeks—usually longer for most SSRIs. With proper training, emergency room physicians can administer ketamine in patients who present with high suicidality, thereby expediting a transition from the emergency department to a psychiatric treatment setting.

Safety Precautions

Because ketamine is a powerful anesthetic, caution is warranted. Respiratory function, CO2 levels, along with vital signs should be monitored during infusion. Those administering ketamine, preferably an anesthesiologist or interventional psychiatrist with training in advanced cardiac life support, can reduce the risk of adverse reactions, as cardiovascular and respiratory emergencies can occur. Because each patient is unique, a thorough work up prior to infusion provides valuable information regarding risks, dosage and treatment frequency to maximize response and minimize adverse events.

Why Does This Matter?

As stated, the suicide rate for depressed adults is now over 15% and survey data shows that as many as 20% of high school students are depressed and have considered or attempted suicide. So far, the best available evidence suggests that Ketamine produces a very strong and rapid antidepressant effect. Ketamine may be a harbinger of newer and more effective treatments for depression. As a result, some of the elite psychiatric training programs are offering Fellowships in Interventional Psychiatry with specific training in TMS and Ketamine infusion.

The lack of data on long-term efficacy and safety is of concern and demands caution. Clearly more research is needed to address these gaps in knowledge and to provide additional safety guidelines for clinicians.