What Is Ketamine?
Ketamine (Ketalar) is widely known as a quick-acting prescription sedative used in humans for minor surgery and in animals as a tranquilizer. It has also garnered a reputation as a party drug (dubbed Special K or vitamin K), because when it’s taken illegally and recreationally at high doses, ketamine causes hallucinations similar to those experienced with LSD. While there was some consideration of ketamine’s antidepressant potential back in the 1970s when it was first approved by the U.S. Food and Drug Administration (FDA), it wasn’t until the mid-1990s that the depression-treatment lightbulb truly turned on. At that time, Yale University researchers noted that chronically depressed patients experienced rapid relief from symptoms after taking ketamine. This observation then spurred a placebo-controlled study published in 2000 in Biological Psychiatry, which found that individuals experienced significant improvements in depressive symptoms within just 72 hours of receiving a ketamine infusion. “The discovery of ketamine’s rapid-onset antidepressant properties is perhaps the most important breakthrough in the treatment of depression in 60-odd years,” says Gerard Sanacora MD, PhD, a professor of psychiatry at the Yale University School of Medicine and the director of the Yale Depression Research Program in New Haven, Connecticut.
How Does Ketamine Work?
Unlike traditional antidepressants that affect the release of neurotransmitters, such as serotonin, norepinephrine, and dopamine, it’s thought that ketamine may act more directly on parts of the brain that are commonly associated with depression, notes Steve Levine, MD, a psychiatrist and CEO of Actify Neurotherapies in Princeton, New Jersey, a national mental health treatment practice that offers ketamine therapy. Further, he explains, there is particular interest in ketamine’s ability to target a glutamate receptor in the brain, which stimulates production of proteins that affect the brain’s ability to change. It’s possible that this more direct mechanism of action explains the more rapid onset of action, as opposed to weeks or months with traditional antidepressants such as selective serotonin reuptake inhibitors (SSRIs), which need to build up in your system in order to impact depression. “Since improvements with ketamine can be seen within four hours of initial dosing, the treatment may be especially effective in rapidly reducing suicidal ideations,” says Dr. Sanacora. In addition to the fast-acting nature of ketamine, it also has the potential for long-lasting effects, even though the drug itself does not linger in the body for long. “This is actually one of the most exciting aspects of ketamine,” says Sanacora. “However, it is important to note that for many people, some level of repeated dosing does seem to be required to maintain the benefit.” And that benefit is promising: Seventy to 85 percent of patients with severe depression who have tried ketamine treatment say that it’s effective, notes research out of Baylor College of Medicine in Houston.
What Exactly Does Ketamine Treatment Entail?
First, patients should meet with a board-certified psychiatrist for a full consultation and evaluation. “If treatment is deemed appropriate, each session lasts approximately two hours,” notes Dr. Levine. This consists of:
Meeting with the psychiatrist before starting that day’s sessionA 40-minute ketamine infusionAbout 45 minutes of recovery timeA second meeting with the psychiatrist
“Talk therapy along with ketamine is very important,” says Levine. “During the IV infusion, patients are awake, but can feel floaty, disconnected, and have a heightened perceptual experience” (meaning it can feel trippy). But as long as patients are well-prepared for the experience, they tend to tolerate it well. “By the time they leave the office, they’re back to how they felt when they walked in, and hopefully they’ll start to see the benefits in the hours to days after,” he says. Typically, there’s an induction or acute phase of ketamine treatment in which patients undergo three sessions in the first week, two in the second week, and then begin tapering off. “We’ll go to once weekly for the next three weeks, then wait two weeks for the next treatment, then wait three weeks, then at least a month,” says Levine. If someone requires ongoing maintenance treatment, the average time between treatments is one month. Soon, however, there may be another option: a ketamine nasal spray. Janssen Pharmaceutical Companies, part of Johnson & Johnson, has recently submitted a new drug application to the FDA for the use of esketamine (a component of ketamine) in a nasal spray for treatment-resistant depression in adults. The drug has been granted the “breakthrough therapy designation” by the FDA, meaning it’s been fast-tracked for approval. (At the same time, the injectable drug rapastinel — from Allergan — has also been fast-tracked. While this medicine is chemically different from ketamine, it works in a similar fashion.) “Although it will initially be reserved for those who have tried other first-line treatments, once approved, these drugs certainly have the potential to move up the chain to first-line depression treatment in the future,” says Levine.
Is Ketamine Safe?
Ketamine side effects are typically limited to the time of infusion and include:
Dissociative or hallucinogenic experienceBlurry visionMild nauseaBriefly elevated blood pressureHeadache
There is the potential for bladder, liver, or cognitive damage with the high-dose, frequent use seen in substance abusers, but these effects have not been reported with the doses and frequency typically used to treat depression, notes Levine. There is potential for abuse and addiction with ketamine. “That’s one of the reasons it’s extremely important to carefully screen and select appropriate patients and restrict access to ketamine to a controlled medical setting, meaning no take-home medicine,” says Levine. Under these conditions, the risk of abuse is quite low.
Who’s the Best Candidate for Ketamine Therapy?
Typically, appropriate candidates have tried — and not responded to — at least two other trials of treatment. “In general, we do not treat those with schizophrenia; current manic episodes as part of a bipolar disorder; clinically significant substance abuse; or unstable cardiovascular disease,” says Levine. Potential candidates include those with:
DepressionBipolar depressionPTSDOCDSome pain disorders like fibromyalgia
“While there are some compelling reasons to consider ketamine in the postpartum period for depression, as of yet, we do not have direct studies of that at this point,” says Levine.
Is Ketamine a Cure for Depression?
“For most people, ketamine therapy does not appear to be a curative treatment,” notes Sanacora. “In other words, despite evidence showing that improvement in depressive symptoms can last several days after a single treatment — or even several weeks to months following a series of treatments — most patients require some ongoing treatment, sometimes with other forms of antidepressant treatment, too.”
