You obtain consent for general anesthesia from your patient with treatment-resistant major depression undergoing electroconvulsive therapy (ECT). Afterward, the patient asks about a ketamine infusion instead of ECT. According to a recent noninferiority trial comparing interventions for treatment-resistant major depression (without psychosis), which of the following outcomes is MOST likely in patients who receive ketamine infusion compared with those who receive ECT?

  • □ (A) Lower posttreatment memory function
  • □ (B) Noninferior treatment response
  • □ (C) Fewer dissociative events

Depression occurs in 21 million American adults and, unfortunately, antidepressant treatment proves to be inadequate for approximately one-third of patients. The term treatment-resistant major depression refers to the situation when a patient has been unresponsive to treatment with two or more antidepressants. Options for treatment-resistant major depression include ECT and ketamine infusion (typically 0.5 mg/kg). ECT requires general anesthesia, has a negative social stigma attached to it, and may lead to cognitive impairment. Ketamine infusion can result in cognitive effects, which has limited its use. In particular, ketamine is not administered to patients who suffer from major depression with psychotic features. Due to curiosity about the comparable effectiveness of ECT to ketamine, investigators recently conducted a noninferiority trial to investigate the issue.

This prospective randomized trial was conducted at five sites and compared a three-week treatment of ketamine (two treatments per week, 0.5 mg/kg of ketamine administered) to ECT (three times per week using right unilateral lead placement). Patients were 21 to 75 years of age, had a diagnosis of major depression without psychotic features with inadequate response to two or more antidepressants, and had no contraindications to ECT or ketamine. The primary outcome was a response to treatment, defined as a 50% or greater decrease in depressive symptoms (as determined by a reduction in scores on the Quick Inventory of Depressive Symptomatology-Self-Report, QIDS-SR-16). All patients with an initial response to treatment received six months of follow-up treatment. Secondary outcomes included other treatment-response scale measurements, memory function, cognitive symptoms, and quality of life.

Initially, 403 patients were enrolled (ketamine group, n=200; ECT group, n=203), but 38 patients either never started treatment or had no posttreatment assessment (five from the ketamine group, 33 from the ECT group). Therefore, the modified intention-to-treat population included 365 patients (ketamine group, n=195; ECT group, n=170). The attrition seen in this trial was anticipated and thus was accounted for in the statistical power analysis. Baseline characteristics were not found to be different between groups. A response to treatment occurred in 55.4% of ketamine-treated patients versus 41.2% of ECT-treated patients (difference, 14.2 percentage points; 95% CI, 3.9-24.2), which fell within the noninferiority margin of –10 percentage points. Memory function post treatment was lower and cognitive symptoms were more frequent in the ECT group. Quality of life was not found to be different between groups. Reported dissociative events were more frequent in the ketamine group.

In conclusion, this recent noninferiority study comparing ketamine to ECT for treatment-resistant major depression (without psychosis) found ketamine to be a noninferior intervention. There was significant but expected attrition, which occurred more in the ECT group. ECT led to greater memory loss, and ketamine was associated with more episodes of dissociation.

Answer: B