The “dissociative anesthetic” ketamine is looking increasingly promising as a safe and effective treatment for intractable depression.
A new randomized study by researchers in the United States has shown that ketamine injections are at least as effective as electroconvulsive therapy (ECT) in treating nonpsychotic forms of major depression.
After starting ECT or ketamine therapy, patients in the study reported an almost immediate improvement in their quality of life. Side effects such as nausea and poor memory were common for both treatments, albeit short-lived.
“Statistically, it was a solid finding showing that ketamine was non-inferior to ECT,” says psychopharmacologist Sanjay Mathew of Baylor College of Medicine.
“This study may give clinicians and patients confidence that ketamine is a reasonable and safe alternative to ECT, at least for the short-term management of treatment-resistant nonpsychotic depression.”
For nearly 80 years, ECT remained the gold standard treatment for severe depression that is unresponsive to other treatments or drug therapies, making ketamine the first real contender ECT faced.
Historically, ketamine has been used in clinical settings for sedation and pain relief because it lulls patients into a trance-like state of euphoria.
However, the psychoactive substance has also shown some notable mental health benefits in recent years.
Clinical studies have shown that a low-dose infusion of ketamine given over about an hour can relieve symptoms of depression for weeks at a time. This is remarkable, given that many antidepressants take about a month to kick in with less potent effects.
The initial studies of ketamine were so promising that in 2019 the United States Food and Drug Administration approved a ketamine-based nasal spray for sufferers of intractable depression and chronic suicidal thoughts.
Previous studies comparing ECT and ketamine have found each therapy safe and effective in treating resistant depression. But while some studies suggest that ECT is “significantly superior” to ketamine when it comes to remission, other studies indicate that ketamine retains 90 percent of the effect seen from ECT treatments.
The latest US study comparing the two treatments used a larger sample size and focused only on non-psychotic forms of depression.
Interestingly, when the researchers randomly divided patients into two treatment groups, ECT or ketamine injections, those assigned to the ECT group dropped out at a higher rate.
This may have to do with the fact that ECT requires general anesthesia, whereas ketamine injections take about 40 minutes and can be given while the patient is awake.
Ultimately, the study saw 158 patients with resistant depression receive three weeks of ECT three times a week and 180 patients receive three weeks of ketamine injections twice a week.
These patients were enrolled for the study at several institutions along the East Coast, including Yale University, Johns Hopkins and Baylor College of Medicine.
Several days after the three-week treatment, the patients filled out questionnaires about their mental health.
The treatment was considered a success when a patient’s depression severity scores decreased by at least 50% from the start of the trial.
Ultimately, 55% of the patients responded to the ketamine treatments, while 41% responded to the ECT treatments.
Moderate to severe side effects were slightly more common in the ECT group at a rate of just over 30%.
“ECT is often used for suicidal patients in hospital settings, so now we need to do a large-scale comparison of ketamine to ECT for our most critically ill and suicidal patients,” says Mathew.
Previous studies have shown that ketamine can rapidly reduce suicidal thoughts in more than two-thirds of patients, suggesting this new form of treatment could save lives.
With so few options available for treating resistant forms of depression, we can’t afford to ignore these clues.
The study was published in NEJ extension.
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