CNECT Blog

"CREST - MST" Study

Thu, 13 Aug 2026 14:12:08 GMT

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

Daniel M. Blumberger et al.

Lancet Psychiatry. 2026;13:376–386.

Research Question

Is magnetic seizure therapy (MST) non-inferior to right unilateral ultra-brief pulse-width electroconvulsive therapy (RUL-UB ECT) for the treatment of major depressive disorder (MDD), while causing fewer cognitive adverse effects?

Study Location

Multicentre randomised controlled trial conducted at three academic centres:

Centre for Addiction and Mental Health (Toronto, Canada)
University of Texas Southwestern Medical Center (Dallas, USA)
University of California, San Diego (USA)

Study Sponsor

· This study was funded by a grant from the NIMH (R01MH112815).

Inclusion Criteria

Participants:

Aged 18 years or older
Diagnosed with non-psychotic major depressive disorder
Baseline Hamilton Rating Scale for Depression (HRSD-24) score ≥21
Considered suitable candidates for convulsive therapy (ECT and MST)
Able to maintain stable antidepressant treatment during the study period

Exclusion criteria

Recent substance dependence in the last 3 months
Significant neurological disease or dementia
Major unstable medical illness
Intracranial metal implants
Requirement for anticonvulsants or high-dose benzodiazepines (>2 mg lorazepam equivalent daily)

How Many Participants

292 participants assessed for eligibility
239 participants randomised
236 participants received treatment
119 participants received RUL-UB ECT
117 participants received MST
219 participants completed a full course of treatment or achieved remission

Study Intervention

Participants were randomly assigned to receive either MST or RUL-UB ECT until remission, withdrawal, or completion of 21 treatments.

MST characteristics

Twin magnetic coils placed over the frontal midline (Fz position)
Stimulation delivered at 100 Hz
Progressive escalation of train duration
Mean number of treatments: 14.2

RUL-UB ECT characteristics

Right unilateral ultra-brief pulse-width stimulation
Treatment administered at six times seizure threshold
Mean number of treatments: 11.4

Follow-Up

Participants were assessed:

At baseline
Every three or four treatments
At treatment completion
Six months after treatment completion

Endpoints

Coprimary outcomes

Remission of depression (HRSD-24)
Worsening of autobiographical memory (25% reduction from baseline on Autobiographical Memory Test [AMT])

Secondary outcomes

Response rates
Suicidal ideation remission
Anxiety symptoms
Quality of life
Subjective adverse effects
Neurocognitive performance
Time to reorientation after treatment

Results

Depression outcomes

Remission rates:
RUL-UB ECT: 27.8%
MST: 22.5%
Absolute difference: 5.3% (non-inferiority margin was 15%)
MST met criteria for non-inferiority.

Response rates

RUL-UB ECT: 48%
MST: 47%

Suicidal ideation remission

RUL-UB ECT: 48%
MST: 48%
Non-inferiority established.

Cognitive outcomes

Autobiographical memory worsened (binary outcome defined as a worsening from baseline of at least 25% in the AMT total score) in:

17.3% of RUL-UB ECT patients
2.7% of MST patients (p = 0.0003)

Compared with ECT, MST was associated with better outcomes in:

Global cognition (MoCA)
Verbal learning and memory
Attention
Executive function
Verbal fluency
Time to reorientation after treatment

Adverse effects

Compared with MST, RUL-UB ECT was associated with higher rates of:

Memory impairment
Jaw pain
Headache
Confusion

However, MST was associated with more post-treatment breathing difficulties.

There were:

13 serious adverse events overall
No treatment-related deaths
No suicide-attempt-related outcomes

Other Relevant Information

Approximately 82% of participants had failed at least two antidepressant trials.
Around one-third had previously received repetitive transcranial magnetic stimulation (rTMS).
Most participants were treated as outpatients.
Participants with psychotic depression were excluded.

Limitations

Target recruitment was not achieved.
The COVID-19 pandemic disrupted recruitment and treatment delivery.
The trial excluded psychotic depression.
Participants were younger than those typically treated with ECT.
Electrode placement was not changed to bilateral treatment in ECT non-responders, reducing generalisability to routine clinical practice.

Summary and Implications

This trial demonstrated that MST produced antidepressant effects that were statistically non-inferior to RUL-UB ECT while causing substantially fewer cognitive adverse effects. Although remission rates (approximately 20-30%) were lower than anticipated in both groups, MST appeared to better preserve autobiographical memory and was associated with reduced transient cognitive side-effects while maintaining efficacy.

The findings suggest that MST could become an important alternative for patients who might otherwise decline ECT because of concerns regarding memory impairment and other cognitive adverse effects. Wider implementation will depend upon regulatory approval, clinician training, and further studies examining long-term outcomes and optimisation of treatment protocols.

Comments

Magnetic seizure therapy (MST) has been in development for over two decades and this study was the largest randomised controlled trial to-date. Rather than passing electrical current diffusely through the brain, MST induces therapeutic seizures using strong focused magnetic stimulation, which results in highly focalised brain stimulation compared with ECT, which instead generally stimulates the whole brain. This approach theoretically can preserve efficacy while reducing cognitive adverse effects, particularly by minimising stimulation of memory related brain regions. The current results suggested broadly similar antidepressant effects of MST compared to right unilateral ultrabrief ECT (RUL UB ECT), the type of ECT which shows the slowest antidepressant effects, though has the best cognitive side-effect profile relative to other types of ECT.

There are several considerations related to this study and its primary findings, both clinically and from a research perspective.

Both ECT and MST were well-tolerated by participants
While the study results support the utility of MST as a potential viable alternative to RUL UB ECT, for example, in people who refuse ECT and are non-psychotic, it does not support the use of MST as an alternative to ECT as treatment is most typically given in clinical practice. This is due to both how ECT was administered (i.e., with no change of electrode placement allowed due to minimal response and treatment continuing to up to 21 treatments) and the study population (mostly outpatients, overall younger relative to a more typical ECT population and all with non-psychotic depression).
The low remission rates with both treatments generally do not support the use of both treatment approaches in this sample with these clinical characteristics (see above).
It is also important to note that while the overall remission rates were broadly similar at post treatment, MST overall required a higher number of required treatments (mean 14.2 MST vs 11.2 ECT treatments) for participants to either achieve remission or complete the entire treatment protocol of up to 21 treatments. Thus, when considering whether to refer patients for MST, clinicians and patients would need to weigh the necessity for speed of antidepressant effects against risk for adverse cognitive effects.
Last, due to the choice of the primary cognitive outcome measure in the study, the Autobiographical Memory Test (AMT), unfortunately, the cognitive results from this study with MST cannot be directly compared with other seminal studies of ECT, which predominantly have used the Columbia Autobiographical Memory Questionnaire – Short Form (C-AMI-SF). Retrograde autobiographical memory side effects are the most persistent adverse cognitive effect of ECT, while other adverse cognitive side effects are mostly transient. To establish whether MST definitively has a more favourable cognitive profile compared to RUL-UB-ECT and other forms of ECT, longer term follow-up data using the C-AMI-SF would be required.

When ECT Becomes Palliative Care: What a Cohort Study Reveals

Wed, 13 May 2026 13:08:02 GMT

Gregg A. Robbins-Welty et al.
Journal of the Academy of Consultation-Liaison Psychiatry. 2025;66:215–223.

DOI: 10.1016/j.jaclp.2024.12.001

“Patients who receive PECT experience reduced suffering and improved QOL. PECT may be helpful in scenarios of life-threatening psychiatric illnesses, terminal medical illnesses with comorbid treatment-refractory psychiatric illnesses, and diagnostic uncertainty with MNCD.”

Research Question

What are the indications, outcomes, and treatment characteristics of palliative electroconvulsive therapy (PECT) in patients with serious medical illness?

Study Location

Single-site retrospective cohort study at Duke University.

Inclusion Criteria

Patients with serious medical illness who:

received an ECT consultation between 2018 and 2023, and
had either palliative care involvement or DNAR status.

How Many Patients

31 patients met inclusion criteria.

21 patients received ECT
10 patients did not proceed with ECT.

Study Intervention

Patients underwent electroconvulsive therapy according to clinical indication.

Common indications included:

Catatonia (64.5%)
Treatment-resistant depressive disorder (35.5%)

ECT characteristics:

Mean acute course: 15 treatments
Mean maintenance course: 26 treatments
Most patients received ECT with palliative intent (81%)
Surrogate decision-makers consented in 76.2% of cases

Medical comorbidities frequently complicated management but often did not preclude ECT.

Follow-Up

Retrospective chart review covering treatment episodes from 2018–2023.

Endpoints

Primary descriptive outcomes included:

Psychiatric symptom improvement
Functional improvement
Cognitive outcomes
Quality of life (QOL)
Safety and complications
Diagnostic clarification

Results

All 21 patients who received ECT experienced psychiatric symptom improvement.
Catatonia patients demonstrated a mean Bush-Francis Catatonia Rating Scale improvement of 17 points (range 8-30; n = 14).
Patients with persistent major neurocognitive disorder (MNCD) demonstrated a mean Montreal Cognitive Assessment (MoCA) improvement of 5 points (range 0-17; n = 8).
Five patients previously diagnosed with were reclassified as depression-related cognitive dysfunction.

ECT improved:

communication (71.4%)
oral intake/hydration (66.7%)
activities of daily living/function (57.1%)
ECT was associated with reversal of life-threatening weight loss in approximately 20% of some patients.
ECT-related complications were uncommon:
one aspiration pneumonia
one episode of bradycardia
No deaths were attributed to ECT.

Other Relevant Information

Many patients had severe medical comorbidities including cancer, heart failure, cirrhosis, COPD, and failure to thrive.
Some patients required ICU-level monitoring during ECT.
Catatonia was frequently under-recognized and misdiagnosed as dementia.
Palliative care consultations were commonly triggered by psychiatric complications such as inability to eat, failure to thrive, or goals-of-care decisions around ECT.
The study highlights the importance of collaboration between consultation-liaison psychiatry and palliative care.

Limitations

Small sample size.
Single-center retrospective design.
Potential selection bias.
Reliance on chart documentation and subjective review of clinical improvement.

Summary and Implications

Palliative ECT appears to be a safe and effective intervention for selected patients with severe psychiatric illness in the setting of serious medical disease. In this cohort, ECT consistently improved psychiatric symptoms, cognition, communication, oral intake, and overall quality of life, while causing few complications.

ECT may also assist diagnostically, particularly in distinguishing depression-related cognitive dysfunction and catatonia from irreversible dementia. The study supports closer collaboration between palliative care and consultation-liaison psychiatry and suggests that ECT should be considered as a palliative intervention when severe psychiatric symptoms contribute substantially to suffering or functional decline.

Comments

Electroconvulsive therapy (ECT) is often framed as a treatment aimed at full remission: for instance, resolving catatonia, lifting severe depression, or stabilizing psychosis. But on medical inpatient units, in the intensive care unit, and alongside palliative care teams, the goal is sometimes different. In such settings, it may be clinically appropriate to prioritize the relief of suffering, restoration of communication, and improvement in eating and drinking. This study addresses that under-discussed clinical reality by describing “palliative ECT” for patients with limited medical prognosis.

Consider ECT as a palliative intervention when the goal is relief of suffering and restoration of function, even if full remission is unlikely. For select patients, ECT may be indicated to improve communication, eating and drinking, basic functioning, and time spent out of the hospital.
When “dementia” is diagnosed in the setting of rapid decline, withdrawal, poor intake, or immobility, keep catatonia and severe depression with cognitive impairment high on the differential—this cohort included multiple cases where cognition improved substantially after ECT.
Medical complexity should trigger careful planning (including higher-acuity monitoring when needed), not automatic exclusion; complications were uncommon and no deaths were attributed to ECT in this series.
Strong collaboration between patients, surrogate decisionmakers, consultation-liaison psychiatry, palliative care, anesthesia, and the ECT service is essential for shared decision-making aligned with patient goals.