Chapter 15. Ketamine

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This activity invites you to test the claim that ketamine, sometimes sold illegally as the street drug "Special K," is a promising treatment for depression. First, you’ll hear three audio clips from a radio show that interviewed a patient who benefited from ketamine and a scientist who studies ketamine. You will then examine the current evidence about the effectiveness of ketamine as a treatment for depression, and consider alternative explanations for these findings. Finally, you will evaluate sources for information about how well ketamine works as an antidepressant.

Can a street drug treat depression? In the chapter on therapies, you learned about a promising new treatment for depression, an experimental drug called ketamine (Singh & others, 2017; Loo, 2018). Ketamine is used legally as an anesthetic, but it is better known as the illegal party drug Special K. More recently, people suffering from depression have been treated with lower doses of the drug with surprisingly successful results. For many people, ketamine reduces symptoms of depression very quickly, but its use is controversial (Zarate & others, 2006).

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Let’s explore the controversy surrounding ketamine. We’ll start by playing you audio clips from a news show on National Public Radio. First, you’ll hear from Christopher Stephens (pictured below), a 28-year-old special-education assistant and martial arts instructor who lives in northern California. Stephens tells reporter Jon Hamilton that he had tried about ten different antidepressants or anti-anxiety drugs; many had negative side effects and none reduced his depression. In fact, his depression become so deep, Stephens started considering suicide. Let’s listen.

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As you learned in the chapter on therapies, many antidepressants affect serotonin, and some affect both serotonin and norepinephrine. But Dr. Zarate, the brain scientist to whom Stephens was referred, has a different idea. Let’s hear again from reporter John Hamilton talking about Dr. Zarate.

Let’s listen to another audio clip. This one discusses the evidence for ketamine as an antidepressant. It begins with Dr. Zarate.

In these early studies, ketamine relieved depression within hours for many people suffering from depression. Unfortunately, ketamine can have serious side effects. For example, the table below lists side effects reported in one study of ketamine as an antidepressant (aan het Rot & others, 2010). We pick up the audio clip with Dr. Zarate again.

Let’s look at one of the ketamine experiments. Dr. Zarate led a study of 18 patients who were diagnosed with major depression and had been treated unsuccessfully with antidepressants at least twice (Zarate & others, 2006). Through random assignment, Dr. Zarate placed these 18 patients in one of two groups—9 received ketamine and 9 received a placebo. The study was double-blind; neither the patients nor their doctors knew which they had received.

Following treatment, the researchers measured patients’ levels of depression. The researchers’ operational definition of depression was the patients’ scores on a standardized test of depression symptoms.

Dr. Zarate’s study found “dramatic” results (Zarate & others, 2006). Less than two hours after treatment, patients who received ketamine were significantly less depressed, on average, than those who received placebo. More than a third of the ketamine patients maintained this improvement, compared with the placebo group, for a week or longer. You can see Zarate’s results in the graph here. The shaded portion indicates where the two groups were significantly different. Remember, this is based on just one dose of ketamine. This study, and others, do indeed support the effectiveness of ketamine as an antidepressant, at least in the short term (Singh & others, 2017). And a short-term success might give patients a chance to get a longer-term treatment started with antidepressants that can take weeks to begin working.

Is ketamine really a fast-acting antidepressant? Or is there another explanation? Maybe it’s a placebo effect—and we don’t mean the actual placebo. We’ll explain. People who take ketamine almost certainly feel its effects. And the researchers used a saline solution as the placebo, which would not have a noticeable effect. So, Dr. Zarate’s study may not have been truly “double-blind”: Both the participants and the clinicians probably realized exactly who received ketamine or a placebo, which may have affected each participant’s response.

Instead of saline solution as a placebo, other researchers suggest using “an active control,” a substance with noticeable effects. They could use, for example, a substance similar to ketamine, such as another anesthetic, that doesn’t affect the glutamate system (aan het Rot & others, 2010). This would make it more difficult for the participants and researchers to know who was in the ketamine condition or in the control condition.

Ketamine has received a lot of press for its potential as a fast-acting antidepressant. And research does seem to support its effectiveness, at least as a short-term solution (Andrade, 2017). The problem is that ketamine is not approved for use as an antidepressant by the U.S. Food and Drug Administration (FDA) and is still considered experimental as a treatment for depression. So, there are currently no federal guidelines for its use (Ryan, 2017). Moreover, most of the evidence for ketamine as a treatment for depression is based largely on “testimonial and anecdote” (Stix, 2013). In the words of one researcher, “enthusiasm for ketamine as an antidepressant has run ahead of the evidence” (Andrade, 2017).

Ketamine is legitimately prescribed as an anesthetic, though, so physicians may legally prescribe it “off label” to people suffering from depression. This allows pop-up clinics to offer off-label ketamine prescriptions at hundreds of dollars a dose, which are usually not covered by insurance (Pollack, 2014).

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Pop-up clinics offering off-label ketamine to treat depression have become a lucrative business, and advertising encourages the use of ketamine for this purpose. Just look at the mock ad below, which is based on real ads for ketamine clinics. Ads like this often provide vague or misleading information about ketamine. Read the ad, and then read the text in the accompanying bubbles to learn how each of the ad’s statements is potentially problematic.

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You just read about several ways in which important information was not provided by the mock ad for a ketamine clinic. The bottom line is that the people who run the clinic may have conflicts of interest. Those who run the clinics may be motivated by the desire to help patients, or they may be motivated by the desire to make money. In the meantime, research continues, and one day ketamine or a new drug aimed at the glutamate system may become available as a treatment for depression. In the meantime, if you or a loved one is diagnosed with depression, think like a scientist as you consider possible treatments.

Here’s one final word about using ketamine for treating depression: We do not endorse the off-label use of ketamine for treating depression, particularly because there is currently little information on its long-term effects (Loo, 2018; Schwartz & others, 2016). And the street drug version of ketamine can be downright dangerous. If you are suffering from depression, seek reputable mental and physical healthcare providers.

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