Is Ketamine a Future Option?

Few treatments are available for people whose depression doesn't improve after trying multiple therapies. For these "treatment-resistant" patients, an intravenous dose of ketamine, a drug usually used for anesthesia during surgery, might someday be an option.

Small studies suggest that ketamine reduces depression symptoms rapidly and dramatically in people for whom other treatments don't work. Whether these effects last very long is not known, however, because long-term ketamine use has not been studied. The drug also has several potentially serious side effects.

Below, Dr. Karen L. Swartz—author of The Johns Hopkins White Paper Depression and Anxiety—answers questions about using ketamine to treat depression and what researchers still need to learn about it.

Q. What options are available for people with treatment-resistant depression?

A. Someone with depression is considered treatment-resistant if he or she does not improve after taking two or more complete courses of a prescription antidepressant.

For these patients, doctors might prescribe combinations of medications, such as two antidepressants or an antidepressant plus lithium or a neuroleptic medication. Doctors may also recommend a treatment that electrically stimulates the brain, such as electroconvulsive therapy. Even after these treatments, some people still don't get better.

Q. What do researchers know about ketamine and its ability to treat depression?

A. Researchers believe that unlike most antidepressants—which mainly target chemicals called serotonin and norepinephrine—ketamine might relieve depressive symptoms by acting on the neurotransmitter glutamate.

In several randomized, placebo-controlled studies, researchers found that an intravenous infusion of ketamine significantly improved depression symptoms in people with treatment-resistant depression. This improvement typically occurs quite rapidly—within 40 minutes to 1 hour—and lasts for several hours to several days.

Ketamine has also been shown to relieve depression specifically in people who weren't helped by electroconvulsive therapy, and to reduce suicidal thoughts in people with bipolar depression.

It's important to remember that so far, studies of ketamine for depression have been very small and very short, involving fewer than 20 patients who were followed for hours to a few days after receiving just one dose of ketamine. Ongoing ketamine treatment for depression has not been thoroughly evaluated.

In a preliminary study, 10 treatment-resistant patients whose depression improved after a single dose of ketamine received six doses over 12 days. All but one remained depression-free. These results need to be repeated in larger, long-term, randomized controlled studies.

Q. How would ketamine compare with other depression treatments?

A. Advantages include ketamine's quick action and strong effects. Even short-term relief might be desirable for people with long-term depression who haven't improved with other treatments. Doctors might be able to use ketamine to give severely depressed patients temporary relief until a traditional antidepressant begins to work, which can take weeks.

Disadvantages include a number of serious side effects, such as hallucinations, high blood pressure, confusion, fear or anxiety, memory loss and dissociation, which is a feeling of being detached from your body and your surroundings. Less serious side effects include dizziness, nausea and headache.

The doses of ketamine that lowered depression symptoms in studies were smaller than those administered when the drug was used as an anesthetic, and theoretically, this might lower the risk of side effects. Because ketamine is administered intravenously, patients would need to visit a doctor to receive treatment, and may need to do so often if ketamine's benefits are only short-lived.

It is important not to view ketamine as a "miracle treatment." More research is needed to determine how and when it might best be used.

Publication Review By: Karen L. Swartz, M.D.

Published: 19 Jun 2013

Last Modified: 19 Jun 2013