Confirmatory efficacy and safety trial of magnetic seizure therapy versus right unilateral ultra-brief electroconvulsive therapy in depression (CREST-MST): a randomised, double-blind, non-inferiority trial in Canada and the USA.

Summary

In a multicenter, randomized, double-blind non-inferiority trial, MST achieved depression remission rates non-inferior to RUL-UB ECT (difference 5.3% favoring ECT; non-inferiority met) while causing substantially fewer autobiographical memory deficits (2.7% vs 17.3%). More ECT recipients discontinued due to non-serious adverse events, supporting MST’s favorable risk–benefit profile.

Key Findings

• MST remission rates were non-inferior to RUL-UB ECT (difference 5.3% favoring ECT; non-inferiority achieved, p=0.048).
• Autobiographical memory worsening was markedly lower with MST (2.7%) than with ECT (17.3%).
• Treatment discontinuations due to non-serious adverse events were more common with ECT (12 vs 3 in MST).

Clinical Implications

MST can be offered as an alternative to RUL-UB ECT, especially for patients prioritizing cognitive preservation or those refusing ECT, with anesthesia teams anticipating similar convulsive therapy workflows but reduced cognitive risks.

Limitations

• Enrollment ended before planned sample size; generalizability limited by predominantly White population
• Short-term outcomes during acute treatment phase; longer-term relapse and cognitive trajectories not reported

Future Directions

Head-to-head cost-effectiveness studies, longer-term cognitive and functional outcomes, and implementation studies to integrate MST into clinical pathways.