Magnetic seizure therapy (MST) matched electroconvulsive therapy (ECT) in treating major depression, while offering a cognitive safety advantage.

In the first noninferiority study comparing the two approaches, 28% of patients receiving right unilateral ultra-brief ECT (RUL-UB ECT) achieved remission vs 23% of those receiving MST, meeting criteria for noninferiority. About half of the patients in both groups showed a meaningful clinical response, in what was largely a treatment-resistant population.

MST was also noninferior to RUL-UB ECT for remission of suicidal ideation. In addition, MST participants experienced fewer cognitive side effects — a typical concern for those undergoing ECT.

“This is a very difficult to treat patient population meaning that have already failed numerous trials of antidepressant medications and other neuromodulation modalities. And so the fact that the RUL-UB ECT comparison group is almost identical in terms of response — that is 50% improvement in depressive symptoms — is a signal that this treatment is as effective,” study investigator Zafiris Daskalakis, MD, PhD, professor and chair of the Department of Psychiatry and Dr Igor and JoAnn Grant Endowed Chair at UC San Diego School of Medicine, told Medscape Medical News.

The study was published online on April 15 in The Lancet Psychiatry.

ECT Side Effects a Concern for Patients

ECT is considered the gold standard for severe, treatment-resistant depression. However, patient concerns about cognitive side effects — particularly memory loss — remain a major barrier.

MST is a new form of convulsive therapy that uses a magnetic field rather than an electrical current, which may allow for more targeted brain stimulation. Previous research indicates that MST is linked to antidepressant effects and few cognitive side effects.

In the largest randomized trial of MST to-date, the investigators included 239 patients with major depressive disorder (MDD) who were randomized to receive treatment with RUL-UB ECT (mean age, 46 years; 80% White individuals; 55% women) or MST (mean age, 45 years; 85% White individuals; 60% women). Participants were enrolled in the trial from 2018 to 2024.

Exclusion criteria included substance misuse in the past 3 months, urgent medical illness, primary diagnosis of obsessive-compulsive disorder or posttraumatic stress disorder, probable neurologic disorder, or substantial cognitive impairment.

MST was delivered using the MagPro XP with a twin coil in a midline frontal position. RUL-UB ECT was delivered using the MECTA spECTrum 5000Q or the SigmaStim Sigma.

Participants received up to 21 treatment sessions or until they achieved remission. Both participants and outcome assessors were blinded to the treatment assignment.

Remission was classed as a Hamilton Rating Scale for Depression 24-item (HRSD) total score ≤ 10 and 60% reduction from baseline scores on two consecutive assessments. The noninferiority margin was a 15% absolute difference in remission rates.

Autobiographical memory was a coprimary cognitive outcome measure, defined as a 25% reduction on the autobiographical memory test.

Secondary outcomes included response on the HRSD (≥ 50% reduction in total score from baseline), the Scale for Suicidal Ideation, Brief Symptom Inventory Anxiety section, Clinical Global Impressions-Improvement Scale, Quality of Life Enjoyment and Satisfaction Questionnaire, and the Columbia ECT Subjective Side- effects Schedule.

Additional outcomes including cognitive function, memory, processing speed, verbal fluency, and executive function were also assessed. The investigators conducted an intention to treat (ITT) sensitivity analysis using logistic regression where early dropouts were included.

Significantly Less Memory Loss

Results showed there was a 5% difference in remission rates, with 28% of RUL-UB ECT participants achieving remission compared with 23% of MST participants. MST was noninferior to ECT (P = .048; 95% CI, -4·4 to 14·9). In the ITT analysis, the difference in remission rates was 4%, favoring ECT.

Although the margin was wide for remission, Daskalakis noted the number of patients who achieved better than 50% efficacy between the two treatments was nearly identical, suggesting similar overall clinical benefit.

Adverse events occurred more often in the ECT group, although most were mild in both groups. During the study, 12 participants in the ECT group and three in the MST group withdrew due to nonserious adverse events.

ECT participants experienced worse autobiographical memory (17.3%) compared with 2.7% of MST participants (P = .0003). For secondary cognitive outcomes, ECT participants generally scored worse while MST patients remained stable or improved.

Remission of suicidality was 48% in both the ECT and MST groups, meeting criteria for noninferiority (P = .033). Secondary HRSD-24 response rates likewise supported noninferiority, reinforcing the primary findings. 

“Collectively, the overall risk-benefit profile of MST supports its consideration as a first-line convulsive therapy in MDD, particularly in those who refuse RUL-UB ECT,” the investigators concluded.

Future research will examine MST in patients with psychotic depression and explore the neural mechanisms underlying its efficacy and cognitive effects, Daskalakis said.

Study limitations included failure to reach the planned sample size of 260 participants and insufficient power to evaluate sex or gender differences.

‘A Reasonable Second Choice’

However, the noninferiority margin for depression remission should be interpreted with caution, Sarah Kayser, PD Dr med, Department of Psychiatry and Psychotherapy at the University of Tübingen in Tübingen, Germany, noted in an accompanying editorial.

While a margin of 15% is clinically substantial, the upper bound of the CI is close to this margin at 14.9%, which leaves “little margin between statistical acceptance and clinical concern.”

“If confirmed in clinical practice, MST could represent a step toward reconciling therapeutic potency with cognitive safety — and restoring meaningful patient choice to a treatment long defined by its tradeoffs,” Kayser and colleagues wrote.

Mark George, MD, a psychiatrist and professor of psychiatry and neurology at the Medical University of South Carolina in Charleston, South Carolina, echoed Kayser’s concern, noting that the large margin also gives him pause.

While George is not entirely convinced of the noninferiority result, he said the findings suggest that MST may be a good option for some patients.

“What they’re saying is maybe it’s not something that we would use instead of the standard, but in patients who were saying I don’t want [ECT] because of cognitive concerns, it seems like a reasonable second choice and I agree with that,” he told Medscape Medical News.

He also questioned the low rates of ECT response as past studies have shown rates of 60% and above. The authors noted that the remission rate may be lower than expected because they excluded patients with psychotic depression and the average patient age was lower than in previous trials.

The study was supported by the National Institutes of Mental Health. The equipment used in the study was supplied by Magventure. George declared having no relevant disclosures.