ECT and MST Trials Show Cognitive Safety Advantage for MST

Key Takeaways

• In the larger randomized trial, MST was non-inferior to right unilateral ultra-brief pulse ECT for major depressive disorder.
• In the smaller bipolar pilot, symptom improvement was broadly similar, while MST showed less autobiographical memory worsening, faster reorientation, and fewer acute safety signals.
• Investigators linked MST’s overall risk-benefit profile to patients reluctant to undergo ECT because of cognitive concerns, while findings from the bipolar pilot remained preliminary.

Clinically meaningful autobiographical memory worsening occurred in 2.7% of MST patients and 17.3% of ECT patients in the 239-patient major depression trial. Both convulsive therapies also meaningfully reduced depressive symptoms. A Brain & Behavior Research Foundation summary paired those results with a smaller bipolar depression pilot, where the balance between antidepressant benefit and cognitive tolerability was also central.

The bipolar depression study was a double-blinded pilot that recruited 55 patients, with 27 randomized to ECT and 28 to MST. Analyzable data were available for 45 participants, and the cohort included 35 patients with bipolar I disorder and 20 with bipolar II disorder. Treatment continued until remission, dropout, or a maximum of 21 sessions, and investigators described the group as relatively young with substantial treatment resistance. The sample was too small to establish MST noninferiority statistically.

Depressive symptoms improved with both treatments, and remission occurred in 6 of 20 patients receiving ECT and 5 of 25 receiving MST. Clinically significant autobiographical memory worsening affected 6 of 22 ECT recipients and 2 of 28 MST recipients, while reorientation averaged 19 minutes after ECT and 7 minutes after MST. Both treatments also reduced suicidal ideation, but four serious adverse events occurred only in the ECT group, which also had more early dropouts. In this pilot, the cognitive and short-term tolerability pattern favored MST even as antidepressant effects appeared broadly similar.

The larger CREST-MST trial enrolled 239 patients across three academic centers in Canada and the U.S. and compared MST with right unilateral ultra-brief pulse ECT. In major depressive disorder, MST was non-inferior to ECT, with remission rates of 22.5% for MST and 27.8% for ECT. MST also outperformed ECT on global cognition, verbal learning, verbal fluency, executive function, time to reorientation, and subjective cognitive complaints. The randomized trial showed a pattern of comparable antidepressant effect with lower cognitive burden for MST.

Investigators interpreted the overall risk-benefit profile in relation to patients who refuse ECT because of cognitive concerns. They also noted that some patients with a strong preference for MST declined participation because randomization could assign them to ECT. Across the two studies, MST was associated with lower cognitive burden, while antidepressant outcomes were not uniformly superior to ECT.