2023-10-25 22:21:00
Image of ketamine, the anesthetic that took an interesting turn in psychiatric research since the early 2000s
(HealthDay News) – The recreational drug ketamine has received much attention for its potential to help people with severe, persistent depression who have not responded to other treatments. But a new study has found that the drug’s effect might be in the minds of the patients who take it.
Stanford Medicine researchers administered ketamine or a placebo to 40 patients with depression who were already receiving anesthesia while undergoing surgery. Importantly, none of the patients or their doctors knew whether they had received the drug or the placebo.
What the team found was a surprise: People in both groups reported a large improvement in depression symptoms. “What we expected was that the patients who received the placebo… would continue not to improve long following their procedure and infusion and that the patients who received ketamine would improve,” said the study’s lead author, Dr. Theresa Lii, a postdoctoral fellow. at the Heifets Laboratory at Stanford Medicine in California.
”That’s what we predicted. And actually, what really surprised us is that everyone improved,” Lii said. One explanation might be that something more nebulous, perhaps a person’s hope and expectations, play a role in the drug’s success, the authors suggested.
Patients assessed using the Montgomery-Åsberg depression rating scale, a key instrument in research (Europa Press)
Ketamine is an anesthetic developed in the 1960s. In the early 2000s, a psychiatrist began testing the drug on patients with treatment-resistant depression and these patients quickly went into remission, Lii said. ”Since then, research has taken off in the field of psychiatry, really trying to replicate the near-miracle of ketamine in resistant depression,” Lii said.
Lii and Dr. Boris Heifets, assistant professor of anesthesiology, perioperative and pain medicine, wondered whether giving ketamine might help patients undergoing surgery feel less depressed following their procedures. The researchers also thought the surgery aspect might be a way to actually test ketamine blindly.
Among the ways the researchers assessed what happened, they used what’s called the Montgomery-Åsberg Depression Rating Scale. They assessed patients one day following treatment using this scale and found that depression scores decreased, on average, by half. That finding persisted during the two-week follow-up.
This means that the patients later had depression that might be classified as mild, compared to the debilitating depression they felt before their surgeries. The researchers do not believe that surgery and general anesthesia were the reasons for the change, as previous studies have not seen an improvement in depression due to surgery. Instead, they credit the role of positive expectations and the care they received from their clinical team.
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Patients who had greater improvement in depression scores were more likely to think they had received ketamine, implying that they expected to improve. The authors noted that this result might be called hope, placebo effect, or expectancy bias. ”It’s not a trivial thing to take someone who has been poorly served by the mental health system and give them hope that something good might happen, and then give them an experience to tie it to,” Heifets said.
With the results and design of the study, it doesn’t definitively answer the question of whether there was any real effect of ketamine or if it was all a placebo effect. But the placebo effect isn’t necessarily what the average person might think it is, Lii explained.
”I think a more technical term, but one that’s not as stigmatizing, is something we often refer to as non-specific effects. And that covers a wide range of things,” Lii said. It may be the expectations that patients have. It may involve the interactions a participant has with their care team. And all of that can lead to people feeling better, she added.
Ketamine is a drug that is not without risk, and there has been a proliferation of unsupervised prescribing of the drug, Heifets said. What this trial shows is that a key to success with ketamine is these non-drug factors, such as setting expectations and close clinical monitoring, she added. Heifets said there may be some physiological reaction between hope and ketamine. That may involve the brain’s opioid receptors, which are involved in pain processing, according to the researchers.
The relationship between hope, expectation and response to treatments, a connection still under study (Illustrative Image Infobae)
The trial results also suggested that the antidepressant response is not really linked to the psychic experience of the drug, said study co-author Dr. Alan Schatzberg, a professor of psychiatry and behavioral sciences at Stanford Medicine. “I think that’s very important,” Schatzberg said. That patients who felt their depression was reduced assumed they received ketamine shows that expectancy bias is critical, he said.
The findings were published Oct. 19 in the journal Nature Mental Health. ”I think I’m actually happy to know that the more we see our patients and interact with patients, if that’s actually the cause of the confusion in this data, then I’m happy that you say that the more we take care of our patients, the more they get better ” said Dr. Lisa Harding, an intervention psychiatrist at Depression MD in Connecticut.
Harding does a lot of work with ketamine for those with treatment-resistant depression and suicidal ideation specifically. She did not participate in this investigation. Harding also noted that the general public thinks of a sugar pill when they hear the word placebo, but that there are many non-medical interventions that can change a person’s mood. ”And it’s not that there’s no effect happening,” Harding said. “Something has happened.”
Harding said it should be a lesson that no ketamine care should be given in isolation. ”I think that’s the main lesson of this study, that the treatment environment matters, the experience of the staff around the treatment is what matters,” Harding said. Research has shown that regarding a third of patients treated with antidepressants will not respond to them, she added. Ketamine acts on the brain in a different way than antidepressants. “I tell patients that instead of working on the juice of the circuit, we are working on the circuit itself,” Harding explained.
More information The US National Institutes of Health has more information regarding ketamine for depression.
SOURCES: Theresa Lii, MD, postdoctoral fellow, Stanford Medicine, Calif.; Boris Heifets, MD, PhD, assistant professor, anesthesiology, perioperative and pain medicine, Stanford Medicine, Calif.; Alan Schatzberg, MD, professor, psychiatry and behavioral sciences, Stanford Medicine, Calif.; Lisa Harding, MD, psychiatrist, Depression MD, Milford, Conn.; Nature Mental Health, October 19, 2023.
*Cara Murez. Health Day Reporters © The New York Times 2023
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