Can the Pain Medication Ketamine Also Relieve Depression?

Ketamine, a drug that is used primarily as an anesthetic and pain reliever, may show some promise as a potential treatment for depression, a new study suggests.

Ketamine is not an approved treatment for depression, but the researchers at the University of California, San Diego used a novel approach to study whether the drug exhibits an antidepressant effect: They looked at symptoms of depression reported by people who had been given ketamine as a treatment for chronic pain, and compared them with depression symptoms in people who were given other pain medications, according to the findings published yesterday (May 3) in the journal Scientific Reports.

The analysis found a 50 percent drop in people's reports of their depression-related symptoms with ketamine, compared with the use of other pain medications, said lead study author Ruben Abagyan, a professor of pharmacy at the Skaggs School of Pharmacy and Pharmaceutical Sciences at the University of California, San Diego. [7 Ways Depression Differs in Men and Women]

Ketamine is typically used as an anesthetic in hospital emergency rooms, and is typically given intravenously or intramuscularly, Abagyan told Live Science. It acts quickly to relieve pain, and can produce a trance-like state in patients, he said.

However, oral or intranasal forms of ketamine are also used illegally as a street (or recreational) drug, and are known to cause hallucinations, Abagyan said. The street drug is sometimes called Special K. [7 Odd Hallucinations]

Reverse methodology

Doctors who have used ketamine with their patients who have chronic pain have observed its fast-acting qualities, and a few physicians have experimented with using it intravenously for patients with depression who have not been helped by other treatments, the study authors wrote.

The two to three weeks it takes for other drugs that treat depression to work can be a long time for a patient who has depression accompanied by suicidal thoughts, according to the study authors. Live Science previously reported that ketamine can produce an antidepressant effect within two hours.

There have been a few, very small clinical trials that have suggested that ketamine is an effective approach for people with treatment-resistant depression, bipolar depression and major depression with suicidal thoughts, but there is a lack of evidence from a large-scale clinical trial, Abagyan said.

As a first step toward accumulating statistical evidence of ketamine's possible antidepressant effects on a large-scale population level, the researchers turned to the more than 8 million patient records in the Food and Drug Administration's Adverse Event Reporting System.

Although this large FDA database was designed to collect data from physicians, pharmacists, patients, family members and lawyers on a medication's negative effects after a drug has been approved for use, it also contains information about general side effects and complaints, the study authors said. [7 Bizarre Drug Side Effects]

The researchers used an inverse-frequency methodology, Abagyan said. Instead of looking for an increase in complaints on the harmful effects of a drug, they looked for whether there was a decrease in depression symptoms as the beneficial effects of a drug, he said.  

Unintended effects

The researchers developed a mathematical formula to compare data from about 41,000 patients who used ketamine for chronic pain any time during the first three months of 2004 and the first three months of 2016, with about 239,000 patients who used other pain medications during these same periods.

Besides discovering that ketamine had an antidepressant effect, the results also revealed that the patients who were given ketamine for pain relief were less likely to have constipation, vomiting and nausea, three side effects often linked with the use of opioid drugs for pain. But ketamine did have some negative side effects, such as kidney failure, low blood pressure and fevers.

Ketamine was not the only drug to display some antidepressant effects. The researchers also identified three others drugs that may also have this unintended effect on depression, Abagyan said. These three included Botox, the botulinum toxin often used to improve the look of wrinkles and treat migraines; minocycline, an antibiotic; and diclofenac, a type of nonsteroidal anti-inflammatory drug (NSAID).

Now that there is some large-scale evidence that ketamine and these three other medications might be alternative medications for depression, and because many of the existing treatments for depression have not been satisfactory for some people, it might be time to explore the potential benefits of these approaches by moving toward a clinical trial of them, Abagyan said.

A clinical trial is necessary to establish what dose of ketamine may work for people with depression, and the best method to administer the drug, as well as to figure out the drug's possible mechanism of action, he said. 

Originally published on Live Science.