Intravenous ketamine is effective for treating depression but is inferior to electroconvulsive therapy (ECT), new research suggests.
In the first head-to-head trial, ECT was more effective than intravenous ketamine in hospitalized patients with severe depression, with higher remission rates and a greater reduction in symptoms.
However, ketamine led to remission in nearly half of participants and is a “valuable” option for treating severe depression, particularly in younger patients, the investigators noted.
The high rate of remission for ketamine infusion “indicates that it definitely can be used in a clinical setting, but it is more probable that a patient will achieve remission with ECT compared to ketamine,” principal investigator Pouya Movahed Rad, MD, PhD (pharmacology), senior consultant and researcher in psychiatry, Lund (Sweden) University, said in an interview.
Results of the KetECT study were recently published online in the International Journal of Neuropsychopharmacology.
Primary focus on remission
The parallel, open-label, noninferiority study included 186 patients aged 18-85 years who were hospitalized with severe unipolar depression and had a score of at least 20 on the Montgomery-Åsberg Depression Rating Scale (MADRS).
Participants were randomly allocated (1:1) to thrice-weekly infusions of racemic ketamine (0.5 mg/kg over 40 minutes) or ECT. All patients continued to take their antidepressant medication during the study. The primary outcome was remission, defined as a MADRS score of 10 or less.
Results showed the remission rate was significantly higher in the ECT group than in the ketamine group (63% vs. 46%, respectively; P = .026). The 95% confidence interval of the difference in remission rates was estimated between 2% and 30%.
Both ketamine and ECT required a median of six treatment sessions to induce remission.
Post-hoc analysis indicated that age was a factor in the findings. In the ECT group, remission was significantly more likely in older patients (51-85 years), compared with younger patients (18-50 years), with remission rates of 77% and 50%, respectively.
But the opposite was true in the ketamine group, with significantly higher remission rates in younger versus older patients (61% vs. 37%).
The study results also support the safety and efficacy of ketamine in patients with psychotic depression, which was present in 15% of patients in the ECT group and 18% of those in the ketamine group.
In this subgroup, half of patients with psychotic depression remitted after ketamine, with no indications of adverse reactions particular for these patients. The remission rate with ECT was 79%.
During the 12-month follow-up period, rate of relapse among remitters was similar at 64% in the ECT group and 70% in the ketamine group (log rank P = .44).
Let the patient decide
As expected, ECT and ketamine had distinct side effect profiles. Subjectively reported prolonged amnesia was more common with ECT and reports of dissociative side effects, anxiety, blurred vision, euphoria, vertigo, and diplopia (double vision) were more common with ketamine.
“Dissociative symptoms were, as expected, observed during treatment with ketamine, but they were brief and in the majority of cases mild and tolerable,” Dr. Movahed Rad said.
The investigators noted that participating study sites all had long-time experience with ECT but no experience administering ketamine.
“Staffs, and some patients, were familiar with side effects common to ECT but were less prepared for the adverse psychological effects of ketamine. This, and knowing ECT was available after the study, probably contributed to the higher dropout rate in the ketamine group,” they wrote.
If both ECT and ketamine are available, “the patient’s preference should, of course, be taken in account when choosing treatment,” said Dr. Movahed Rad.
“ or other somatic risk factor. Patients who have not responded to ECT or have had unacceptable side effects should be offered ketamine infusion and vice versa,” he added.