Evidence from multiple studies suggests that an intravenous (IV) infusion of ketamine, a drug that for decades has been used for anesthesia, may rapidly relieve symptoms of major depression, particularly in people who aren’t helped by established treatments. Although ketamine has not been approved by the FDA specifically for treating depression, doctors are permitted to prescribe medications off label at their discretion—and some do so with ketamine.
Now, unregulated ketamine clinics for treating depression have cropped up throughout the United States, raising concern about the absence of standardized treatment guidelines and the lack of proof regarding ketamine’s safety and effectiveness over the long term.
Since 2000, many studies of varying quality have found that ketamine can effectively relieve depression. A meta-analysis published in 2015 in The American Journal of Psychiatry examined 12 ketamine studies. The authors found that a single IV infusion of ketamine could quickly alleviate symptoms of depression when used by itself or in addition to another drug or electroconvulsive therapy (ECT). The analysis indicated that ketamine use in conjunction with ECT was associated with a significantly greater reduction in depressive symptoms after an initial ECT session.
The improvement in depressive symptoms typically occurs within a few hours of receiving an infusion, peaks after one day, and wears off within three to 12 days. A few small reports suggest that repeated infusions can extend the benefits for at least several weeks.
Despite this encouraging initial evidence, all ketamine studies to date have had some substantial limitations: The studies included small numbers of participants and were conducted over short periods of time, so researchers can’t be sure about how effective or safe ketamine is when used for extended periods.
Some researchers believe ketamine for depression might be relatively safe because the dosage used is much lower than the dosage given when the drug is used as anesthesia. But there is no information on the risks of giving people even low doses of ketamine over an extended time.
When ketamine is used to treat depression, the most common side effects are drowsiness, dizziness, poor coordination, and blurred vision. Less common but more serious possible effects include dissociation (an “out-of-body” experience), hallucinations, confusion, delusions, and increased blood pressure. These effects typically peak within two hours of receiving an infusion and subside in four to 24 hours.
The U.S. Drug Enforcement Administration categorizes ketamine as a controlled substance. Some people take ketamine recreationally for its euphoric effects, and ketamine abuse is a widely recognized problem. People who use ketamine recreationally can develop tolerance (meaning they need to take increasingly larger doses of the drug) and possibly psychological dependence.
No guidelines for ketamine and depression
About 60 to 100 ketamine clinics operate within the United States. Some are in a hospital or surgical center, but most (74 percent) are in a doctor’s office. No government agency or medical organization has established guidelines for how doctors should use ketamine to treat depression.
In response to growing use of the drug and safety concerns, the American Psychiatric Association issued a statement on the use of ketamine for treating severe depression. Although not an official guideline, the statement, published in JAMA Psychiatry in 2017, recommended that before treatment, a doctor should:
- Perform a comprehensive assessment of the patient’s depressive symptoms and check for a history of substance abuse or other psychiatric disorders.
- Confirm that standard treatments for depression were not effective for the person.
- Evaluate the individual’s overall health and the possible risks of ketamine treatment for that person.
The statement suggested that a standard dose of 0.5 milligrams per kilogram of a patient’s weight be given as a 40-minute infusion. Some limited evidence suggests that ketamine treatments should be given twice a week for up to four weeks.
There are no training requirements that doctors or other clinicians need to complete before using ketamine to treat people with depression. In some clinics, the treatment may be given by a psychiatrist who routinely evaluates and treats people with depression. That’s not always the case, however. A survey found that 67 percent of clinicians who provide ketamine treatment for depression are psychiatrists, 23 percent are anesthesiologists, 4 percent are emergency medicine physicians, and 4 percent are family doctors.[inset:4663]
Is ketamine right for you?
If you are thinking about ketamine treatment, start by discussing it with your doctor. With an understanding of your overall physical and mental health, your doctor will be able to determine which treatments are best for you and if ketamine might be appropriate. Generally, doctors will consider ketamine only for someone whose depression did not improve after trying several other, more thoroughly studied treatments.
If ketamine is an appropriate option, your doctor may be able to recommend a provider. Be wary of selecting a ketamine clinic by searching online. Several websites provide directories of ketamine clinics or doctors, but it is not clear how the providers included in such directories were evaluated.
Other considerations before starting ketamine treatment are:
- Determine which type of doctor will provide the treatment. Although anesthesiologists may have experience with administering ketamine before surgery, a psychiatrist will be better able to handle a psychiatric emergency if one occurs. Make sure the thorough evaluation described earlier is part of the treatment plan.
- Ensure that the doctor or clinician who provides ketamine will properly monitor you during treatment and will be able to respond quickly if you develop complications. Your blood pressure, heart rate, and oxygen saturation should be checked before, during, and after the infusion. The clinic also should have emergency resources on hand, such as oxygen and medications for rapidly lowering blood pressure.
- Ask about cost. Considered an experimental treatment, ketamine usually isn’t covered by insurance, and most people pay out of pocket. Each infusion can cost $400 to $1,000, and multiple infusions may be needed. An option is to find a clinical trial recruiting people with depression. The National Library of Medicine provides a large database of ongoing studies at ClinicalTrials.gov. Search for “ketamine” and “depression,” and limit the results to studies seeking participants. Your doctor can help determine if a trial is legitimate and appropriate for you. Beware of research trials that require up-front payments; almost all clinical trials are offered free of charge to patients.
Despite promising initial evidence of ketamine’s effectiveness and the growing popularity of ketamine clinics, using ketamine to treat depression has not been thoroughly evaluated in large, long-term studies. With additional research, doctors will learn more about the long-term risks and benefits and which people might benefit the most. Until then, work with your doctor to determine which depression treatments are best for you.
A version of this article first appeared in the UC Berkeley 2019 Depression and Anxiety White Paper.
Also see First Steps for Treating Depression.