Ketamine May Offer Quick, Effective Relief For Major Depression

At any given time, about 1 in 10 people in North America and similar numbers in Europe suffers from clinical depression, and the overwhelming majority of these patients are given antidepressants of the selective serotonin reuptake inhibitor (SSRI) class — such as Prozac.

However, a drug that is used for anesthesia in hospitals and as an illegal hallucinogen at raves and on the street may offer an answer for hard-to-treat cases of depression in which other medications have proven to be ineffective.

Mayo Clinic Researchers Investigate Ketamine for Depression

Researchers at the Mayo Clinic recruited patients whose depression had not responded to other medications to participate in a clinical trial involving ketamine, a pain killing drug that is also known as "special K" on the streets, where it is sold as a recreational drug.

Ketamine relieves pain. In large doses, it can cause hallucinations, elevated blood pressure, bronchodilation, and a condition known as dissociative anesthesia, in which sight and sound are distorted and the user may experience dream-like states or trances, the loss of sensation without the loss of consciousness. The Mayo researchers tested the drug to see if smaller doses could relieve refractory, treatment-resistant depression.

Volunteers with refractory depression were given intravenous infusions of the drug for 100 minutes twice a week until their depression symptoms lifted or they had had four treatments. Half of the volunteers were essentially depression-free in two weeks or less while on this experimental treatment regimen. Two of the volunteers for the study remained depression-free for an entire month without taking any additional medications.

An "Evanescent" Response

Dr. Timothy Lineberry, medical director of the Mayo Hospital Psychiatric Clinic and one of the principal researchers in the study, refers to the ketamine treatment as inducing an "evanescent" (bubbly) response.

Because ketamine is readily available, doctors have a lot of experience in dealing with it, and the potential for physical addiction is low, more and more psychiatrists are prescribing the medication "off-label" (its use for treating depression is not approved by the FDA) for patients who have depression that does not respond to other medications.

At the Mayo Clinic, ketamine is not yet the standard treatment for refractory depression. In particular, it is not prescribed for patients who have had prior problems with "party drugs," or for alcoholics. However, pharmaceutical giant Johnson & Johnson is developing a new form of the drug for depression treatment.

Ketamine Taken Through The Nose

Johnson & Johnson has been developing a drug called esketamine that will be taken through the nose. Right now, the clinical trials are using intravenous (IV) esketamine, but the final form of the drug will be administered as a nose drop.

The Johnson & Johnson researchers hope that the nasal formula will minimize some of the more prominent side effects of ketamine, such as hallucinations and anxiety. But for both ketamine and the new drug esketamine there remain some serious, unanswered questions.

As an update, as of 2022, eskamine is widely prescribed to patients suffering from treatment-resistant depression. When other antidepressants fail to improve a person's symptoms of depression, and even when depressed patients suffer from acute suicidal thoughts, esketamine is now prescribed routinely, with good results.

Are ketamine and esketamine appropriate treatments for patients at risk for suicide?

Doctors hope that the fast-acting nature of ketamine and esketamine may make them especially appropriate for sufferers of major depressive disorders who are identified as at-risk for suicide. The major problem for profoundly depressed people seeking relief with ketamine now is that since the drug is used off-label, it is not covered by insurance plans, and each treatment costs thousands of dollars that the patient has to pay out of pocket. Because the drug wears off in a few days to a few weeks, the expensive treatment has to be repeated over and over again. Catastrophic medical bills are also depressing.

What are the long-term effects of ketamine and esketamine?

Another unanswered question for ketamine and esketamine researchers is how these medications affect the course of depressive illnesses over the long-term. Are users of the medication at greater risk for relapse? For "highs" or hypomanic episodes as they rebound from depression? Is it possible to become habituated to the drug so that it loses its effectiveness over time? When the need is immediate and desperate, the doctor may use ketamine anyway, but the wisdom of long-term use is not established,.

Can ketamine or esketamine used to treat depression induce the dreaded "K-hole" side effect?

When taken in large doses, ketamine can induce an out-of-body experience commonly called the "K-hole," in which the user has a sensation of floating, separation from the body, or being dead. There is no way to resist this experience with mental effort, and there are no medications that can stop the experience before the drugs wear off. Whether there is a risk for this side effect when the drugs are used for treating depression remains to be determined.

A more recent study at the Baylor School of Medicine in Houston and the Mt. Sinai School of Medicine in New York City, however, produced even more excitiing results. In this study, most participants in the study experienced complete relief from depression after just one 40-minute IV, and 46% were depression-free a week later.

Just remember that the effects of ketamine are unpredictable. Drug pushers who sell special K at parties don't pay careful attention to dosing, expiration dates, or purity of the drug, and it is far too easy to overdose when taking the drug in an illicit setting.