Professor Paul Fitzgerald
Monash Alfred Psychiatry Research Centre
Monash University School of Psychology and Psychiatry
beyondblue Victorian Centre of Excellence
Project completion year
Electroconvulsive therapy (ECT) remains the only established therapy for the large percentage of patients with depression who fail to respond to standard treatments. It is commonly used but has substantial problems, including the occurrence of cognitive side effects that are often highly distressing for patients.
The development of a new treatment with similar efficacy but which minimises these side effects would have great clinical value. One highly promising possibility is magnetic seizure therapy (MST). MST involves replacing the electrical stimulation used in ECT with a magnetic stimulus. This appears to be able to produce similar clinical effects but without the disabling cognitive side effects related to ECT. The researchers had previously completed an open label pilot study of MST, which clearly indicated antidepressant effects and no MST-related cognitive side effects. This pilot study aimed to directly compare the clinical response to MST in patients with TRD to that achieved with ECT.
Additionally, the aim of the study was to continue to investigate the safety of the procedure especially in relation to memory and cognitive side effects. Should MST be shown to have similar efficacy to ECT but with reduced side effects, it is envisioned that it could rapidly replace ECT in clinical practice throughout Australia, and indeed internationally, with substantial ongoing benefits to patients. Due to the rarity of the equipment available so far, MST research is only being undertaken in a handful of places internationally and the team of researchers are the only group to do so in Australia.
The study involves a randomised double-blind clinical trial with two treatment arms. This means that patients are randomly assigned to receive a treatment course of MST or ECT. Patients and raters do not know which type of treatment is being received. Other parameters of the trial include:
- subjects have moderate or severe depression
- patients will be between the ages of 18 and 75
- a total of 60 patients will undertake a treatment course of between nine and 15 treatments
- baseline and end-point assessments will be undertaken to investigate efficacy and will include clinical assessments, cognitive assessments and neurophysiological assessment
- response in the clinical trial will be assessed with standard instruments. MST or ECT to be administered three times per week using standard equipment and techniques. The primary outcome is the percentage of patients meeting response criteria on depression severity rating scales.
The aim this project was to, via an open label pilot trial, investigate the clinical response to MST in patients with treatment-resistant depression who would otherwise have been referred for ECT.
A total of 13 participants with Major Depressive Disorder were enrolled in the study, full data was available for 12 participants. Following a course of MST, five of the 12 participants met full response criteria (reduction of 50 per cent on their depression rating scale), four more participants had a reduction of between 20 and 50 per cent, and three participants were non-responders.
No evidence was found of any impairment of cognition, in particular memory, despite the conduct of a neuropsychological battery of greater breadth than is typically used in ECT research. In regards to immediate post MST effects, the patients awoke from the anaesthetic fully oriented in a manner notably different from what it typically seen post ECT.
Finally, 10 of the enrolled patients also underwent pre- and post-PET scans to investigate changes in brain metabolism following MST. Areas of increased metabolism after treatment were seen in the Basal Ganglia (specifically the Globus Pallidus, Substanita Nigra, Putamen), the Orbital Frontal Cortex, Medial Frontal Cortex and Dorsolateral Prefrontal Cortex. There were more regions with increased activity in the left hemisphere than the right. There were no regions of decreased metabolism.
The PET results indicate primarily that MST-affected brain regions are implicated in depression, more specially regions that are consistent with the Limbic-Cortical Dysregulation Model of depression. In particular, the most replicated finding in depression treatment studies was found to be an increase in metabolism in frontal brain regions.
There were also some differential findings in brain activation between responders and non-responders, which may be indicative of a restoration of balance in responders, rather than the increases in brain activation seen across the board in non-responders. However, the sample sizes are too low to make firm conclusions at this stage.
Implications for policy and practice
The positive findings of the pilot study provide clear impetus for the research to move to the next stage required in the assessment of the efficacy of this novel treatment, i.e. a randomised controlled trial of MST vs ECT.