Confirmatory Efficacy and Safety Trial of Magnetic Seizure Therapy Versus Right Unilateral Ultra-Brief Electroconvulsive Therapy in Depression

Overview

Magnetic seizure therapy (MST) is an emerging form of convulsive treatment for severe depression. Like electroconvulsive therapy (ECT), it induces a controlled therapeutic seizure, but it uses a magnetic field rather than electrical current to stimulate the brain. The hope has been that MST could preserve the strong antidepressant effects of ECT while reducing memory and other cognitive side effects.

This confirmatory trial, called CREST-MST, compared MST with right unilateral ultra-brief pulse-width electroconvulsive therapy (RUL-UB ECT), a form of ECT already designed to reduce cognitive burden. The study was conducted in Canada and the United States and focused on whether MST could achieve similar remission rates while causing less worsening of autobiographical memory.

Why this study matters

Major depressive disorder can be disabling, persistent, and life-threatening. For people who do not respond to medications or psychotherapy, convulsive therapies remain among the most effective options. However, many patients hesitate to choose ECT because of concerns about memory loss, confusion, and stigma.

MST was developed to address this problem. Because magnetic stimulation can be targeted more precisely than electrical stimulation, it may trigger seizures in a way that spares memory-related brain regions. If MST works as well as ECT but with fewer cognitive harms, it could become an important first-line convulsive treatment for selected patients with depression.

Study design

This was a multisite, randomized, double-blind, parallel-group, non-inferiority trial. In practical terms, participants were randomly assigned to receive either MST or RUL-UB ECT, and neither the participants nor the assessors knew which treatment they were receiving. The goal was not to prove that MST was better than ECT, but rather that it was not unacceptably worse in antidepressant effectiveness while offering safety advantages.

The trial took place at three academic centers. Adults aged 18 years and older with major depressive disorder were enrolled and treated until they achieved remission, withdrew, or completed up to 21 treatments.

MST was delivered using a twin coil placed in a midline frontal position. This placement was chosen to induce seizures while aiming to minimize stimulation of brain regions important for autobiographical memory. The comparison treatment, RUL-UB ECT, is a modern ECT technique that uses a right unilateral electrode placement and an ultra-brief pulse width to reduce cognitive adverse effects compared with older ECT methods.

Outcomes measured

The study had two primary outcomes.

The first was remission from depression, measured with the 24-item Hamilton Rating Scale for Depression, a widely used clinician-rated scale. Remission means symptoms improved to the point that the person no longer met the threshold for a current depressive episode.

The second was worsening of autobiographical memory, measured with the Autobiographical Memory Test (AMT). Autobiographical memory refers to memory for personal life events, such as specific experiences, places, and people from one’s own past. This type of memory can be especially important to patients, because problems in this area can affect identity, daily functioning, and quality of life.

The study defined clinically meaningful memory worsening as a 25% reduction in AMT performance, which corresponded to about one standard deviation decline.

Participants

Between June 26, 2018, and March 1, 2024, 292 participants were enrolled, and 239 were randomly assigned to treatment. Three withdrew before treatment began. Enrollment ended before reaching the originally intended sample size.

In the RUL-UB ECT group, the mean age was 45.5 years, 80% were White, 55% were female, and 45% were male. In the MST group, the mean age was 44.5 years, 85% were White, 60% were female, and 40% were male. The study population therefore mainly reflected middle-aged adults with treatment-resistant major depression in academic treatment settings.

Main findings

The antidepressant results showed that MST was non-inferior to RUL-UB ECT. Remission occurred in 22.5% of the MST group and 27.8% of the RUL-UB ECT group. The difference favored ECT by 5.3 percentage points, but this difference remained within the study’s predefined non-inferiority margin of 15 percentage points. Statistically, this meant MST met the main criterion for being considered similarly effective for remission of depression.

The cognitive findings were especially notable. Worsening autobiographical memory occurred in 17.3% of participants receiving RUL-UB ECT, compared with only 2.7% of those receiving MST. This difference was statistically significant and strongly favored MST.

In addition, fewer participants stopped treatment because of non-serious adverse events in the MST group than in the RUL-UB ECT group. Specifically, 12 participants in the ECT group and 3 in the MST group withdrew for this reason. This suggests that MST may be better tolerated overall, although both treatments can still cause short-term adverse effects that require monitoring.

Interpretation of the results

The key message from this trial is that MST appears to provide antidepressant efficacy that is close enough to RUL-UB ECT to meet non-inferiority criteria, while causing less worsening of autobiographical memory. That combination is clinically important because it addresses one of the biggest barriers to use of convulsive therapy: fear of cognitive side effects.

For patients with severe major depressive disorder, especially those who are reluctant to undergo ECT because of memory concerns, MST may offer a more acceptable alternative. The results also support the idea that convulsive therapies are not a single uniform treatment; rather, their methods of seizure induction and brain targeting can meaningfully change the balance between benefit and harm.

Clinical significance

In real-world practice, treatment choice for severe depression often involves weighing speed of response, likelihood of remission, and potential cognitive effects. ECT remains one of the most effective options, particularly when depression is severe, psychotic, suicidal, or medication-resistant. However, its use is sometimes limited by patient reluctance and concerns about memory.

This trial suggests that MST could be considered as a first-line convulsive therapy in major depressive disorder, especially for patients who refuse RUL-UB ECT or are highly concerned about cognitive adverse effects. While MST is not yet as widely available as ECT, and implementation depends on specialized equipment and expertise, these findings strengthen the case for broader development and clinical adoption.

It is also important to note that the lower memory burden does not mean zero cognitive risk. Any convulsive treatment can still involve transient confusion, headache, muscle discomfort, or short-term memory difficulties. Careful pre-treatment counseling, anesthesia support, and post-treatment monitoring remain essential.

Study limitations

Several limitations should be kept in mind. First, the trial ended before reaching its planned sample size, which can reduce statistical precision. Second, the study was conducted at academic centers, so results may not fully generalize to community settings. Third, the sample was predominantly White, meaning more diverse populations need to be studied.

Also, while non-inferiority was demonstrated for remission, the remission rates in both groups were not especially high, which suggests there is still room to improve treatment protocols, patient selection, or seizure dosing strategies. Longer-term outcomes, including durability of remission and long-term cognitive effects, remain important questions.

What patients and clinicians should take away

For patients living with severe depression, this study offers cautious optimism. MST may become a valuable option when standard treatments have failed or are not acceptable. It seems to preserve much of the antidepressant power of ECT while offering a more favorable cognitive profile.

For clinicians, the study provides stronger evidence that MST is not merely experimental, but a potentially practical therapeutic alternative. The data support discussing MST with patients who want an effective convulsive treatment but are worried about autobiographical memory loss.

Conclusion

In this confirmatory randomized trial, magnetic seizure therapy achieved non-inferior antidepressant efficacy compared with right unilateral ultra-brief ECT and showed substantially less worsening of autobiographical memory. These findings suggest a more favorable risk-benefit balance for MST in major depressive disorder.

As availability expands and more data accumulate, MST may join the treatment landscape as an important option for people with difficult-to-treat depression, particularly for those seeking effective treatment with less concern about cognitive side effects.