NEW YORK CITY— “When we talked about brain stimulation in psychiatry, we used to mean one thing—electroconvulsive therapy. It was the only tool we had available. However, in recent years, advances have allowed us to stimulate the brain in a more focal fashion than is possible with electroconvulsive therapy,” said Sarah H. Lisanby, MD, Associate Professor of Psychiatry at Columbia University in New York City.

One such method is magnetic seizure therapy, which performs convulsive therapy using rapidly alternating strong magnetic fields. According to Dr. Lisanby, magnetic seizure therapy offers greater control of intracerebral current intensity than electroconvulsive therapy. Dr. Lisanby reviewed her recent study of the safety and feasibility of magnetic seizure therapy in patients with major depression at the 157th Annual Meeting of the American Psychiatric Association.

Indeed, Dr. Lisanby’s study found that compared with electroconvulsive therapy, magnetic seizure therapy seizures had shorter duration, lower ictal EEG amplitude, and less postictal suppression. The study investigators noted that patients had fewer subjective side effects and recovered orientation more quickly with magnetic seizure therapy than with electroconvulsive therapy. Magnetic seizure therapy was also found to be superior to electroconvulsive therapy on measures of attention, retrograde amnesia, and category fluency.

IMPROVING ON ECT

As she explained, magnetic seizure therapy uses “high-intensity repetitive transcranial magnetic stimulation (rTMS), which is used to induce focal seizures from target regions of the superficial cortex. It is done in an electroconvulsive therapy suite, and patients undergo anesthesia, in a similar fashion to electroconvulsive therapy.” Her randomized, within-subject, double-blind study enrolled 10 patients (three male; mean age 46.7) with a major depressive episode. Two seizures were induced with both magnetic seizure therapy and electroconvulsive therapy in each of the 10 patients during a four-treatment course of convulsive therapy; magnetic seizure therapy was administered via a round coil placed on the vertex. A neuropsychological battery and side-effects rating scale were administered before and after each session.

According to Dr. Lisanby, the goal of magnetic seizure therapy is to take what is good about electroconvulsive therapy—that it is the most tested antidepressant treatment—and try to reduce its side effects by focusing the seizure in the parts of the brain that researchers believe are central to antidepressant response; also, it may be possible to eliminate spikes in the regions that may be contributing to side effects, in particular, the temporal lobe.

TARGETED TREATMENT

“So why do we think we need a new seizure treatment? My answer is: Clinically, first of all, although electroconvulsive therapy is our most effective antidepressant treatment, it does have drawbacks in terms of side effects—in particular, the most serious side effect that patients are concerned about is amnesia. Secondly, even though it is our most effective treatment, not everyone responds. Unfortunately, the response rate is not 100%, so any attempts to refine treatment to enhance efficacy could have some clinical value. Scientifically,” she continued, “a focal model of seizure induction allows us to probe systematically what aspects of the seizure may be pointing to that response in the brain.”

THE GOALS OF MAGNETIC SEIZURE THERAPY

The first goal is to maximize response to magnetic seizure therapy based on changes seen in electroconvulsive therapy. “Our hypothesis is that by charting the initiation to the cerebral cortex we may be able to do just that,” she said. Her team found that most reductions occur in the anterior prefrontal cortex and are associated with response to electroconvulsive therapy. Topographical changes show that the prefrontal cortex is associated with antidepressant response to electroconvulsive therapy. “Therefore, we can make the [magnetic seizure therapy] seizure have more of a targeted impact on blood flow and function in the cerebral cortex,” Dr. Lisanby said, and this may be a means of preserving and possibly enhancing any antidepressant effects typically seen in electroconvulsive therapy.

The second goal of magnetic seizure therapy is to lessen side effects caused by convulsive therapy. As Dr. Lisanby reported, the changes in blood flow patterns involve the temporal lobe, which affects measures of retrograde amnesia. Her research team saw structural change in the hippocampus that represented the growth of new synaptic connections in response to the treatment. “This classic change is not found in antidepressant treatment and is thought to be related to some of the anesthetic side effects in electroconvulsive therapy,” she explained. “Therefore, if you can spare the temporal lobe and limit changes in that region and not induce the anatomic changes, we may be able to create a focal anticonvulsant therapy that has fewer side effects.”

THE BENEFITS OF MAGNETIC SEIZURE THERAPY

One of the aspects of magnetic seizure therapy identified as advantageous is that the magnetic fields pass through the scalp and skull without impediments, allowing the researchers to induce small amounts of electricity and to more precisely target regions of the cortex. Also, magnetic fields induced by rTMS do not penetrate at levels high enough to induce neural electroconvulsive therapy deeper than about 2 cm below the scalp at the gray-white matter junction, which is about the level of the superficial cortex, so effects are limited to the cortex. Researchers have better control of the amount of electricity induced, which enhances the potential for inducing focal seizures in a target region such as the prefrontal cortex and limits impact in other regions, such as the temporal lobe.

“We found evidence that magnetic seizure therapy is able to achieve our goal of delivering less electricity to the brain, in particular, to the temporal lobe, than electroconvulsive therapy. More targeted application of electricity translates into more targeted focal seizures,” summarized Dr. Lisanby. “There is less depression in the temporal lobe with magnetic seizure therapy. We also found a difference in the effects of these two treatments on the anatomy of the hippocampus. In particular, there are fewer effects of hippocampal remodeling.”

Now that their study has demonstrated the efficacy of magnetic seizure therapy in treating depression, Dr. Lisanby said that the best site of induction and the correct dosage to maximize efficacy of magnetic seizure therapy should be investigated in additional research. The next step is to compare magnetic seizure therapy to electroconvulsive therapy in a nine-month controlled trial and provide rigorous tests of magnetic seizure therapy as a useful antidepressant strategy.

—Heidi W. Moore

Suggested Reading
Kosel M, Frick C, Lisanby SH, et al. Magnetic seizure therapy improves mood in refractory major depression. Neuropsychopharmacology. 2003;28:2045-2048.
Lisanby SH, Luber B, Schlaepfer TE, Sackeim HA. Safety and feasibility of magnetic seizure therapy (MST) in major depression: randomized within-subject comparison with electroconvulsive therapy. Neuropsychopharmacology. 2003;28:1852-1865.

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