Novel Convulsive Therapy May Cut Suicidal Thoughts in Bipolar Disorder

Fran Lowry

June 04, 2019

SCOTTSDALE, Arizona — Magnetic seizure therapy (MST), a novel convulsive therapy, is effective in treating depression and suicidal thoughts in patients with treatment-resistant bipolar disorder (BD), new research suggests.

In an open-label study, response and remission rates with MST were particularly robust for suicidality, producing remission or clinically significant responses sooner than it did for depressive symptoms.

MST also appears to have a more benign effect on cognitive function than conventional electroconvulsive therapy (ECT).

Dr Victor Tang

"Magnetic seizure therapy is exciting because we are trying to capitalize on what we already know is a very successful treatment for major depression and suicidality, which is electroconvulsive therapy," lead author Victor Tang, MD, Centre for Addiction and Mental Health (CAMH), University of Toronto, Canada, told Medscape Medical News.

Tang noted that ECT "is probably the best antidepressant we have" and one of the main options when patients are treatment resistant to usual therapies with medication or psychotherapy.

"We know ECT is effective, but we are also hopeful that MST will be found to be just as effective but have better acceptability because it has fewer side effects, especially those affecting cognition. Also, there might be less stigma, and other things that people fear about ECT," he said.

The study findings were presented here at the American Society of Clinical Psychopharmacology (ASCP) 2019 annual meeting.

Milder, Fewer Side Effects

ECT applies electrical stimulation through the scalp and the skull.

"The problem with that is you have to really crank up the electrical energy so that it can pass through the skull and into the brain. And because it hits the skull, the skull makes the electricity basically go all over the brain," Tang said.

The benefit of MST is that it is able to skip the skull and can stimulate a specific area of the brain directly, he noted.

"So, while both MST and ECT produce this electrical generalized seizure, with MST, most of the energy is concentrated in one area, such as the cortex, where you want it to be; but it avoids those deeper structures, like the hippocampus, that affect memory and cognitive function," said Tang.

In the open label study, 26 patients with treatment-resistant BP received up to 24 MST treatments in either the frontal (n = 20) or vertex (n = 6) position.

An adequate trial of MST was deemed to be eight treatments, and the full treatment protocol was to receive MST treatments until remission or up to 24 weeks, whichever came first.

The 24-item Hamilton Depression Rating Scale (HAMD-24) was used to assess  remission or response to treatment. Suicidality was assessed with both the Scale for Suicidal Ideation (SSI) and item 3 of the HAMD-24, which reports on suicidal intent.

Remission of depression was defined as a posttreatment HAMD-24 score of 10 or less and at least a 60% decrease in HAMD-24 scores from baseline on two consecutive ratings. Response was defined as at least 50% reduction of depressive symptoms on the HAMD-24 on two consecutive ratings.

Remission of suicidal ideation was defined as a final score of zero on the SSI or HDRS-24, item 3. Only patients with baseline suicidal ideation were included in this analysis.

Patients were assessed at baseline, after every three treatments, and at the end of the treatment course.

Significantly Reduced Symptoms

Patients, on average, showed a significant reduction in their HAMD-24 scores, Tang reported.

In those who completed an adequate trial of eight MST treatments, the remission rate was 23.1% and the response rate was 38.5%. Among those who completed the full protocol, results were even better: their remission rate was 30% and their response rate was 50%.

"This is exciting because most of the time, when people are treatment resistant and are on their 3rd or 4th medication, at that point they really have a 10% or less chance of getting anything from it, so this would definitely be a step up and a good potential  alternative to ECT," Tang said.

MST was even more effective for suicidality, the study investigators found.

SSI remission was seen in 47% of adequate trial completers and 57% of per-protocol completers. The mean number of treatments needed to reach remission from suicidal ideation was 11 and ranged from 2 to 20. By contrast, a mean of 17 treatments was needed to achieve remission or response for treatment resistant depression.

"So it looks like there might be even more of a specific effect for suicidality above depressive symptoms," noted Tang.

The researchers also discovered that coil placement during MST was critical. Overall, frontal placement was significantly better than vertex placement.

For example, among adequately-treated patients, the remission rate was 30% for frontal placement but zero for vertex placement. For full-protocol patients, response rate for frontal placement was 45% vs 17% for vertex placement.

No patients receiving fewer than eight MST treatments had a response or remission in their depression or suicidality, Tang said.

Coil Placement Matters

Commenting on the findings for Medscape Medical News, Zhi-De Deng, PhD, from the National Institute of Mental Health, Bethesda, Maryland, noted the importance of the placement of the coil.

Deng, who was not involved in the research, also said that MST is an experimental technique, with many different parameters to tweak.

Dr Zhi-De Deng

"There is the frequency, or how fast you apply these magnetic pulses. There are also differences in coil placement, as shown in this study. As it turns out, where you place the coil is important, because none of the patients who received vertex placement in the adequate trial group showed remission of their depressive symptoms," Deng said.

"But, they did find that MST relieved suicidal ideation," Deng continued, "and it seems to be efficacious in relieving depressive symptoms in treatment resistant bipolar disorder. The question is: how quickly does it do that?"

In general, full remission with MST requires several more treatment sessions compared with ECT, which typically needs to be given in 10 to 12 treatment sessions, Deng noted.

"The mean number of treatments needed to achieve response and remission with MST  is close to 18. This might make a difference when it comes to suicidal ideation. With ECT, the mean number of treatments needed for SI remission is about 7. So we're looking at 3 weeks vs 2 weeks of treatment until remission. That week may or may not make a difference when it comes to acute suicidal ideation," he said.

MST has a better side effect profile, and this makes it attractive to study, Deng noted.

"You don't stimulate so deep in the brain, and that gives it a better cognitive side effect profile. Time to orientation after treatment is shorter; you get less memory side effects with MST compared to ECT. In terms of speed of response, it's a little bit slower, and yet with an adequately dosed treatment course, you can achieve similar effects to ECT. It's just slightly slower and that may or may not matter in this context of suicidal ideation," he said.

Currently, a multicenter trial is underway comparing ECT and MST head-to-head.

"The goal would be to show that MST is non-inferior to ECT in terms of efficacy for treatment of depression," Deng said. "Eliminating the cognitive side effects of ECT has been a main goal of research. It looks like MST does have a better safety profile."

The study was sponsored by the Temerty and Grant families, and through the Centre for Addiction and Mental Health Foundation and the Campbell Institute. Tang and Deng have disclosed no relevant financial relationships.

American Society of Clinical Psychopharmacology (ASCP) 2019: Abstract 3001798. Presented May 29, 2019.

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