Can ketamine help prevent suicide?
At the Yale Depression Research Program, a clinical trial is underway to help answer that question. It is testing the ability of esketamine, a drug very similar to ketamine, to alleviate suicidal thinking in severely depressed patients.
Ketamine, an NMDA receptor antagonist drug, has been shown to dramatically improve symptoms of major depression. Gerard Sanacora MD, PhD, director of the Yale Depression Research Program and the principal investigator for the Yale site in this national, multi-site study, says the current research has the potential to change the way people are treated in emergency rooms and other settings "in the very near future."
"If it works," he explains, "it will have a profound impact on our ability to help people are who suicidal."
Suicide and depression
Suicide, a significant public health problem in the United States, is closely linked with mental health conditions. Among people who die by suicide, depression is the most prevalent mental health problem. (For additional facts and figures about suicide in the United States, click here.) The current study is limited to patients with diagnosed major depression; participation is by invitation only. For more information, visit clinicaltrials.gov.
Using ketamine to treat depression
The Yale Depression Research Program is affiliated with the Clinical Neuroscience Research Unit (CNRU), Connecticut Mental Health Center's umbrella organization for translational research. In the late 1990s, Yale researchers at the CNRU made the first observation that ketamine, an anesthetic agent, helped depressed patients feel better.
"Unexpectedly, a single dose of ketamine produced a rapid, robust antidepressant response in several patients," recalls Dr. Sanacora. "It started as early as a few hours after the drug was given and lasted for days, or even weeks."
Recently, several ketamine researchers noted independently that people taking the drug showed a large improvement in one main symptom: suicidal thinking. The current study will investigate the effectiveness of a form of ketamine, esketamine, when used intra-nasally for patients with suicidal thoughts or behavior. Ketamine was originally approved by the FDA in the 1970s, primarily for pediatric anesthesia. Its use in depression is still experimental. The suicide prevention study is funded by Jansen Pharmaceuticals.
"It's an exciting study for several reasons," notes Dr. Sanacora. "People with suicidal thoughts are almost always excluded from depression studies because enrolling them has been considered too high risk," he explains.
"This is the first study I am aware of specifically examining a rapid treatment option for patients in an acute suicidal crisis."
"The hope," he continues, "is that we can treat these patients and shorten hospitalization, or possibly avoid hospitalization altogether. The goal is to get people out of their immediate crisis and reduce the risk of self-harm."
A long-term investment in research
Science has always been a fundamental part of the work of Connecticut Mental Health Center (CMHC). A community mental health center jointly run by the Yale University Department of Psychiatry and the State of Connecticut Department of Mental Health & Addiction Services, CMHC was established in 1966 with a tripartite mission in clinical care, education, and research.
Over the years, neurobiological research into the mechanisms of mental illness and potential treatments has involved many people based at CMHC—scientists, doctors, nurses, patients, and others. The long-term commitment of Yale researchers and the State of Connecticut, says Dr. Sanacora, has enabled researchers to reach the point "where we now have actual treatments, coming out of the science, that are having a direct impact on people's lives."
In addition to the suicide prevention study, Dr. Sanacora's program recently received approval for another ketamine study, this one designed to determine the "dose response curve" (appropriate doses) for individuals being treated with the drug. Funded by the National Institute of Mental Health (NIMH), it involves five different sites in the U.S. including the Yale Depression Research Program.
What to do if you're concerned
In his many years of practicing psychiatry, Dr. Sanacora has lost very few patients to suicide, but it has happened. "It's a terrible tragedy for the families and for everybody involved," he says. "Unfortunately, there are many people who aren't being adequately treated, or who are not receiving a significant benefit from their current treatments. These people are at very high risk, and it's difficult to predict whether they are, or will become, suicidal."
The best predictor of a suicide act, he says, is whether a person is talking about suicide or has recently attempted suicide.
Unfortunately, many people with suicidal thoughts do not disclose their thoughts to friends, family, or health professionals, making prevention extremely challenging.
For concerned individuals who suspect that someone they know may be having suicidal thoughts, Dr. Sanacora offers this advice: "If a friend, relative, or acquaintance is talking about hurting themselves, that should be taken very seriously. If this is the case, you should inform whomever you need to inform, including their doctor or clinician, to insure the individual is receiving the care they need. If the situation appears urgent, you should get the person to an emergency room or equivalent setting as soon as possible."
While health care professionals are bound by privacy laws not to reveal patient information without consent, friends and family members are free to inform a provider about a patient's health and wellbeing without violating any laws.
"We need to approach this problem from every angle," says Dr. Sanacora. "We need more providers who know how to work with and are comfortable treating suicidal patients. We also need to raise public awareness and reduce the myths and stigma surrounding suicide. I hope our current studies will contribute to the growing body of knowledge about depression and suicide prevention."