Ketamine Restores Ability to Experience Pleasure in Depressed Patients Within Minutes

Ketamine Psychonaught / Wikimedia Commons

There are many faces to depression: sadness, hopelessness, trouble sleeping, lack of motivation, an inability to experience pleasure.

That last one has a medical name—anhedonia—and people experiencing it often no longer enjoy activities that used to bring happiness. Anhedonia is not found just in depression; it can be an important part of other disorders, including schizophrenia, obsessive-compulsive disorder and addiction.

In a study published this month in Translational Psychiatry, researchers have found that a drug called ketamine can help quickly reverse anhedonia in patients with treatment-resistant bipolar depression (also known as manic-depression or bipolar disorder).

Ketamine has previously been shown to help rapidly reverse other aspects of depression in a number of studies; doctors use the drug to treat patients at several hospitals around the country, although it remains illegal to possess without a prescription and hasn't yet been approved by the Food and Drug Administration for psychiatric purposes. On the party drug circuit it's sometimes called "Special K" and is abused for its anaesthetic and hallucinogenic effects.

The researchers found that a single injection of ketamine led to a significant improvement in normal pleasure-seeking behavior in as little as 40 minutes, and this dramatic improvement lasted as long as two weeks for some of the 36 participants.

"There aren't really any treatments for anhedonia, even in treatment-resistant depression," so it's a big deal to find something that acts in this way, said study author Dr. Carlos Zarate, chief of the experimental therapeutics and pathophysiology branch at the National Institute of Mental Health in Bethesda, Maryland.

Dr. Sanjay Mathew, a psychiatrist at the Baylor College of Medicine who has studied ketamine for treating depression but who wasn't involved in the study, concurred with that assessment, saying he wasn't aware of anything that works in this way, and so rapidly.

Shortly before and after the injections, patients underwent PET scans, which measure brain activity. Zarate and his colleagues found that ketamine increased activity in a part of the brain called the dorsal anterior cingulate cortex, implicated in "guiding reward-based decision making." It also helps different parts of the brain communicate, and Zarate refers to it as a "brain circuit."

This imaging finding "gives us a better sense of the neurobiology of anhedonia," Mathew told Newsweek. Knowing that this part of the brain is involved in anhedonia may help scientists better understand related syndromes in which this condition plays a part, and to develop new treatments for them, he said.

The finding adds to ketamine's already-impressive track record for tackling treatment-resistant depression. Several previous studies, for instance, have found that the drug can reduce the likelihood of suicide and suicidal thoughts amongst depressed patients.

Other researchers are continuing to look into how ketamine works, exactly, but it is known that it modifies how the brain processes a neurotransmitter called glutamate, Zarate said. This, in turn, affects how different parts of the brain communicate with one another. Whereas other antidepressant drugs such as Prozac work by altering levels of neurotransmitters like serotonin, ketamine has a more immediate and direct effect, Zarate said.

"The important thing to me is that ketamine doesn't just lead to improvement on this one scale [of anhedonia] but leads to an improvement in the actual brain circuit," as seen in the PET imaging, Zarate added. "And that's pretty interesting."