Electroconvulsive therapy appears to be more effective than ketamine, according to a randomized controlled trial that examined hospitalized, severely depressed patients. But the findings, published in the International Journal of Neuropsychopharmacology, indicate that both treatment options are relatively safe and valuable tools for treating depression.
Electroconvulsive therapy uses a carefully controlled electrical current to induce controlled epileptic seizure. Ketamine, which is commonly used as general anesthetic, inhibits NMDA (N-methyl-d-aspartate) glutamate receptors in the brain. The drug also has euphoric and dissociative effects, making it a potential drug of abuse. Both treatments have been found to have rapid antidepressant effects.
“As a senior consultant in psychiatry and PhD in pharmacology, I was of course interested and curious about ketamine when the first reports were published about a miraculously fast antidepressant effect, considering that ketamine had a very different mechanism of action compared to all other antidepressants,” said study author Pouya Movahed Rad, a senior consultant and researcher in psychiatry at Lund University.
In the study, hospitalized patients diagnosed with unipolar depression were randomly assigned to receive either electroconvulsive therapy or racemic ketamine infusions. The researchers screened 622 patients for eligibility and included 186 patients who underwent at least one treatment session in the final analyses.
Depression severity was evaluated prior to treatment, 4–5 hours after the first treatment session, the day after each subsequent treatment session, and at follow-ups. A maximum of 12 treatment sessions were administered until maximal antidepressant effect was achieved. At least six sessions on average were required for both treatments to produce a full recovery.
“We did not see the rapid effect of ketamine that other studies have shown. Instead, our results indicate that the effect is cumulative, and increases with the number of treatments. Older people generally responded less well to ketamine, while younger people responded as well to electroconvulsive therapy as to ketamine,” Movahed said.
The researchers found that the remission rate was higher in the electroconvulsive therapy group than the ketamine group. A total of 63% of the patients in the electroconvulsive group recovered after the treatment, compared with 46% among those who received ketamine. During a 12-month follow-up period, 64% of the electroconvulsive therapy group relapsed compared with 70% in the ketamine group.
“If you suffer from severe depression, you should consider and not be afraid of treatment with electroconvulsive therapy. The treatment is safe, incredibly effective and can be life-saving. However, there may be situations where electroconvulsive therapy does not work or cannot be given for various reasons. Then, ketamine can be a suitable alternative,” Movahed told PsyPost.
“Moreover, as a patient and next of kin, you should require that the treatment which is proposed, regardless of whether it is electroconvulsive therapy, ketamine, psychotherapy or common antidepressants should make you well. The goal should be to achieve remission and regain quality of life and function.”
More participants in the ketamine treatment chose to leave the study than those who received electroconvulsive therapy.
“The group we studied had been offered electroconvulsive therapy, but about half of them were now randomized to participate in the intravenous ketamine group. This may have been important because some of the participants chose to discontinue the ketamine treatment prematurely,” Movahed said.
Patients who received electroconvulsive therapy were more likely to report headaches, muscle pain, and amnesia compared to those who received ketamine therapy. Dissociative side effects, anxiety, blurred vision, euphoria, vertigo, and double vision were more common side effects among those in the ketamine group.
“Future studies should investigate if the larger group of less severely depressed patients who gain little benefit from available antidepressants respond as well to ketamine infusions as the current cohort in our study did,” Movahed said. “The role of different variable such as age, cognitive profile, genetics, etc., in predicting response to ketamine and electroconvulsive therapy should also be clarified.”
The study, “Racemic Ketamine as an Alternative to Electroconvulsive Therapy for Unipolar Depression: A Randomized, Open-Label, Non-Inferiority Trial“, was authored by Joakim Ekstrand, Christian Fattah, Marcus Persson, Tony Cheng, Pia Nordanskog, Jonas Åkeson, Anders Tingström, Mats B Lindström, Axel Nordenskjöld, and Pouya Movahed Rad.