A new study suggests that, for some patients, the 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 the two treatments.
Patients who do not respond to at least two antidepressants — in regards to a third clinically depressed patients – have a condition that clinicians call ‘treatment resistant’. Their options for relief are limited. Doctors generally recommend up to 12 sessions of ECT, which have a long-established effectivenessbut is stained with the stigma of historical abuse and scary Hollywood pictures of people tied to tables, writhing in pain. Today’s ECT is much safer and performed under general anesthesia, but the procedure remains underutilized.
The study, published Wednesday in the New England Journal of Medicine, found that ketamine, when given intravenously, was at least as effective as ECT in patients with treatment-resistant depression who do not have psychosis. (For people with psychosis, even very low doses of ketamine can make psychotic-like symptoms worse.)
“The results were very surprising to us,” said Dr. Amit Anand, lead author of the study and a professor of psychiatry at Harvard Medical School who studies mood disorders at Mass General Brigham. His team initially speculated that ketamine would be nearly as effective as ECT. Instead, Dr. Anand said, they found ketamine worked even better than that.
This is important in part because some patients are uncomfortable with the potential side effects of ECT, such as temporary memory loss, muscle pain, or weakness. (In rare cases, this can cause permanent memory gaps.)
The study, which was sponsored by the Cleveland Clinic Foundation, shows that ketamine is easier to administer, with fewer adjustments during treatment and fewer patients dropping out, Dr. Anand said. “More importantly, it shows that ECT, as expected, is associated with memory problems, whereas ketamine is not.” Intravenous ketamine also has side effects, like dissociationbut it’s “usually not an unpleasant experience for patients,” Dr. Anand said.
Previous studies have shown that both treatments can be effective in patients with difficult-to-treat depression, but research has 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.”
“It’s this kind of rigorous, randomized, realistic pragmatic data that is robust and very clinically meaningful,” said Dr. McIntyre.
The researchers randomly assigned intravenous ketamine or ECT to 365 patients. Almost half received ketamine twice a week while the others received electric shock therapy three times a week. At the end of the three-week treatment, 55% of patients in the ketamine group and 41% of patients in the ECT group reported a 50% or greater reduction in symptoms.
Six months later, the quality of life scores of the two groups were similar.
One limitation of the study was that the number of ECT treatments may not have been enough because the treatment period was only three weeks, said Dr. Daniel F. Maixner, ECT program director. to Michigan Medicine at the University of Michigan, which was not affiliated with the study.
Study subjects began their ECT course by receiving electrical currents to one side of the brain, which may take 10 or 12 sessions, as opposed to the nine used in the study, he added. .
“If there’s more improvement to be had, you keep going,” Dr. Maixner said.
Patients starting bilaterallystimulating both sides at the same time, often need fewer sessions. If patients had had more ECT sessions, a greater proportion of them might have responded to treatment, Dr. Anand said, but it also likely would 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, continuing treatment carries additional risks. With ketamine, for example, longer treatment “increases the likelihood of both drug dependence and cognitive adverse effects, including dissociation, paranoia and other psychotic symptoms,” wrote Dr. Robert Freedman, professor of psychiatry at the University of Colorado, in a editorial published with the study.
Earlier 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 hospitalized patients as well as patients with psychotic depression, for whom the ECT appears to be particularly effective.
Researchers and clinicians use off-label intravenous ketamine 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. Among clinicians, intravenous ketamine is widely regarded as as effective or more than esketamine for treatment-resistant depression, Dr. Anand said.
Unfortunately, because intravenous ketamine is a generic drug, “it’s unlikely anyone will try to get FDA approval to make it more reimbursable for insurers,” he added.
Later this year, Dr. Anand and his colleagues will recruit patients for a larger study comparing ECT to intravenous ketamine in 1,500 severely suicidal and depressed patients, most of whom are likely to be hospitalized. They will also look at how the effects differ across age groups, Dr Anand said.
Dr Maixner, of Michigan Medicine, said research suggests that intravenous ketamine, which he has also used to treat patients, may have emerging and significant benefits for difficult-to-treat depression, which “offers options to people”.