A new study suggests that, for some patients, anesthetic ketamine is a promising alternative to electroconvulsive therapy, or ECT, currently one of the fastest and most effective therapies for patients with difficult-to-treat depression.
The study is the largest direct comparison of both treatments.
Patients who don't respond to at least two antidepressants — about one-third of clinically depressed patients — have a disease doctors call "treatment-resistant."
Your options for relief are limited.
Doctors typically recommend up to 12 sessions of electroconvulsive therapy, which has long been proven effective but is tainted by the stigma of its historical misuse and terrifying Hollywood images of people tied to tables, writhing in agony.
Current electroconvulsive therapy is much safer and performed under general anesthesia, but it remains underutilized.
Ketamine a drug used as an antidepressant, Photo: npr.org
The study, published recently in The New England Journal of Medicine, found that ketamine, administered intravenously, was at least as effective as ECT in patients with treatment-resistant depression who do not suffer from psychosis.
(For people with psychosis, ketamine, even at very low doses, can worsen psychosis-like symptoms.)
Hypothesis
"We were very surprised by the results," said Dr. Amit Anand, the study's senior author and a professor of psychiatry at Harvard Medical School who studies mood disorders at Mass General Brigham.
His team had initially hypothesized that ketamine would be almost as effective as electroconvulsive therapy.
However, according to Anand, they found that ketamine was even more effective.
This is important, in part because some patients are uncomfortable with the possible side effects of ECT, such as temporary memory loss, muscle pain, or weakness.
(Rarely, it can cause permanent gaps in memory.)
The study, sponsored by the Cleveland Clinic Foundation, shows that ketamine is easier to administer.
"More importantly, it shows that ECT, unsurprisingly, is associated with memory problems, whereas ketamine is not."
Intravenous ketamine also has side effects, such as dissociation, but this "is not usually an unpleasant experience for patients," Anand says.
Previous studies have shown that both treatments can be effective in patients with difficult-to-treat depression, but those investigations have primarily looked at the two therapies independently.
Dr. Roger S. McIntyre, a professor of psychiatry and pharmacology at the University of Toronto who is not affiliated with the study, called it "groundbreaking."
"This is this kind of rigorous, randomized, real-world pragmatic data, which is robust and very clinically significant," McIntyre said.
The researchers randomly assigned intravenous ketamine, or ECT, to 365 patients.
Nearly half received ketamine twice a week, while the rest received ECT three times a week.
At the end of three weeks of treatment, 55% of patients in the ketamine group and 41% of those in the electroconvulsive therapy group reported a reduction in symptoms of 50% or more.
Six months later, the quality of life scores of both groups were similar.
One limitation of the study is that the number of ECT treatments may not have been enough, as the treatment period was only three weeks, according to Dr. Daniel F. Maixner, director of Michigan Medicine's ECT program at the University of Michigan, who was not involved in the study.
Treatment
Study subjects began ECT treatment by receiving electrical currents on one side of the brain, which may require 10 or 12 sessions, compared with the nine used in the study, he added.
"If there's more improvement, it continues," Maixner said.
Patients who start bilaterally, stimulating both sides at the same time, usually need fewer sessions.
If patients had completed more ECT sessions, it's possible that a higher proportion of them would have responded to treatment, Anand said, but that would also likely have caused more side effects.
A small number of patients in both groups — less than 33% — went into remission, meaning they had only mild depressive symptoms.
This suggests that additional treatments would be needed for patients to maintain relief.
However, continued treatment carries additional risks.
With ketamine, for example, longer treatment "increases the likelihood of both drug dependence and cognitive adverse effects, such as dissociation, paranoia and other psychotic symptoms," Dr. Robert Freedman, a professor of psychiatry at the University of Colorado, wrote in an editorial published with the study.
Previous evidence suggests that remission rates from ECT may be much higher – often at least 60% – but these studies may have included a higher percentage of hospitalised patients, as well as people with psychotic depression, for whom ECT appears to be particularly effective.
Researchers and doctors use intravenous ketamine off-label because it has not been approved by the Food and Drug Administration for the treatment of mood disorders, unlike its cousin esketamine, also known as Spravato, which is administered nasally.
Later this year, Anand and colleagues will recruit patients for a larger study comparing electroconvulsive therapy with intravenous ketamine in 1,500 depressed and acutely suicidal patients.
Maixner, of Michigan Medicine, said research suggests that intravenous ketamine, which he has also used to treat patients, may have some emerging and strong benefits for difficult-to-treat depression, which "gives people options."
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