Electroconvulsive therapy (ECT) is the gold standard treatment for resistant depression, but results of a new randomized, head-to-head trial suggest intravenous ketamine is at least as effective and has fewer side effects.
“The take-home message right now is that if somebody is being referred for ECT, the treating clinician should think of offering ketamine first,” study investigator Amit Anand, MD, professor of psychiatry, Harvard Medical School, Boston, Massachusetts, told Medscape Medical News.
The study was published online May 24 in The New England Journal of Medicine.
“Gold Standard”
More than one third of cases of depression are treatment resistant, said Anand, who is also director of Psychiatry Translational Clinical Trials at Mass General Brigham. He noted that ECT has been the “gold standard for treating severe depression for over 80 years.”
He added that although ECT is very effective and is fast acting, “it requires anesthesia, can be socially stigmatizing, and is associated with memory problems following the treatment.”
An anesthetic agent, ketamine has been shown to have rapid antidepressant effects and does not cause memory loss or carry the stigma associated with ECT, he added. For these reasons, the investigators examined whether it may be a viable alternative to ECT.
To date, no large, head-to-head trials have compared ECT to intravenous ketamine. A recent meta-analysis showed that ECT was superior to ketamine for major depression, but the total number of patients included in the analysis was small, Anand said.
In addition, most of the participants in that trial were drawn from a single center. Approximately 95 patients were enrolled in each arm of the trial, which included some participants with features of psychosis. “ECT is very effective for depression associated with psychotic features, which may be one reason ECT had a better response in that trial,” said Anand.
The investigators compared ECT to ketamine in a larger sample that excluded patients with psychosis. They randomly assigned 403 patients at five clinical sites in a 1:1 ratio to receive either ketamine or ECT (n = 200 and 203, respectively; 53% and 49.3% women, respectively; aged 45.6 ± 14.8 and 47.1 ± 14.1 years, respectively).
Patients were required to have had an unsatisfactory response to two or more adequate trials of antidepressant treatment.
Prior to initiation of the assigned treatment, 38 patients withdrew, leaving 195 in the ketamine group and 170 in the ECT group.
Treatment was administered over a 3-week period, during which patients received either ECT three times per week or ketamine (.5 mg/kg of body weight) twice per week.
The primary outcome was treatment response, defined as a decrease of ≥50% from baseline in the16-item Quick Inventory of Depressive Symptomatology-Self-report (QIDS-SR-16). Secondary outcomes included scores on memory tests and patient-reported quality of life.
Patients who had a response were followed for 6 months after the initial treatment phase.
More Research Needed
Following the 3-week treatment period, a total of 55.4% patients who received ketamine and 41.2% of patients who underwent ECT responded to treatment, which translates into a difference of 14.2 percentage points (95% CI, 3.9 – 24.2; P <.001) ― a finding that fell within the noninferiority threshold set by the investigators.
ECT was associated with decreased memory recall after the 3 weeks of treatment, with a mean (SD) decrease in the T-score for delayed recall on the Hopkins Verbal Learning Test–Revised of -.9 (1.1) in the ketamine group vs -9.7 (1.2) in the ECT group (difference, -1.8 points [-2.8 to -.8]).
Remission, determined on the basis of QIDS-SR-16 score, occurred in 32% of the ketamine group and in 20% in the ECT group. Similar findings were seen on the Montgomery-Åsberg Depression Rating Scale.
Both groups showed significant improvements in quality of life, with changes of 12.3 and 12.9 points, respectively, on the 16-item Quality-of-Life Scale.
“ECT was associated with musculoskeletal adverse events, whereas ketamine was associated with dissociation,” the investigators note.
During the 6-month follow-up period, there were differences in relapse rates between the groups (defined as QIDS-SRS-16 score 11):
| Month | Ketamine group | ECT group |
|---|---|---|
| 1 | 19.0% | 35.4% |
| 3 | 25.0% | 50.9% |
| 6 | 34.5% | 56.3% |
ECT has been shown to be…
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