Stimulation with a low-strength electromagnetic field device immediately improves mood in patients with major depressive disorder (MDD) and bipolar disorder (BPD), new research shows.
Results from a randomized, double-blind, sham-controlled study are exciting, especially because the effects were so rapid, lead author Michael L. Rohan, PhD, a physicist at McLean Hospital and Harvard Medical School, Belmont, Massachusetts, told Medscape Medical News.
"I think we have something that is working on the depressed state in either major depressive disorder or bipolar disorder," said Dr. Rohan. "Whether it's more effective in either one of them, we don't know, but it seems to have an immediate effect on the depressed state."
The device holds "great potential" as a clinical tool for psychiatrists, Dr. Rohan added.
The study was published in the August 1 issue of Biological Psychiatry.
The ability of the rapidly oscillating electromagnetic field, called low-field magnetic stimulation (LFMS), to improve mood was discovered "serendipitously" about a decade ago. Researchers who were carrying out experimental MRI scans to assess brain chemistry noticed changes in depressed bipolar patients.
"The subjects started coming out of the baseline scan with improved mood," said Dr. Rohan.
After further research, Dr. Rohan designed and built the portable tabletop device that is now being studied. It consists of a magnetic coil, an amplifier, a waveform generator, and a computer.
The US Food and Drug Administration (FDA) has determined that the device carries a nonsignificant risk.
Dr. Rohan described the LFMS device as being similar in size and shape to "an old-fashioned mailbox." Patients lie on a bed with a padded headrest. The top of their head fits into the device, leaving the rest of their head, including their eyes, exposed.
Compared with transcranial magnetic stimulation (TMS), which uses electromagnetic pulses to stimulate nerve cells, and electroconvulsive therapy (ECT), which induces "small self-repairing seizures," LFMS uses fields that are "at least 100 times weaker," said Dr. Rohan.
Although ECT is "the most successful treatment for depression," it carries a cost, he said. "Patients come in regularly and they get sedated; the treatments are invasive."
The new study included 63 patients aged 18 to 65 years with BPD or MDD who were stably medicated but still symptomatically depressed and who scored 17 or more on the observer-rated 17-item Hamilton Depression Rating Scale (HDRS-17). Most patients took multiple medications throughout the study.
Patients were randomly assigned to receive 20 minutes of active (n = 34) or sham (n = 29) treatment. The inactive device resembled the real one in every way, down to the faint beeping noise it emitted. Neither the patients nor the operators could tell the difference.
"Because the placebo effect is so high in antidepressant studies, we had to be very careful about that sham," stressed Dr. Rohan. "When you have an exciting new device like this, people have high expectations."
Directly before and after the treatment, the mood of the patients was determined with the HDRS-17 and the self-rated visual analogue scale (VAS), which is designed to be responsive to an immediate change in mood.
The study showed that the mean improvements in VAS score were greater for active compared to sham treatment by 0.8 points for BPD (95% confidence interval [CI], -.6 to 2.1; P = .60), 1.6 points for MDD (95% CI, -.4 to 3.6; P = .17), and 1.1 points for the combined sample (95% CI, .2 to 1.9; P = .01).
Mean improvements in HDRS-17 score were greater for LFMS than for sham by 2.5 points for BPD (95% CI, -1.2 to 6.2; P = .34), 3.2 points for MDD (95% CI, -3.3 to 9.6; P = .74), and 3.1 points for the combined sample (95% CI, .5 to 5.8; P = .02).
Dr. Rohan believes that the differences between active and sham treatments were not significant in the individual diagnostic groups because these groups did not have enough participants. He pointed out that the differences did reach significance when the data were combined across groups.
Mood was also assessed with the self-rated Positive and Negative Affect Schedule (PANAS). There was greater improvement in scores among both BPD and MDD patients receiving the active treatment. In this case, the difference was statistically significant not only for the combined sample but also for BPD patients alone, although not for MDD patients alone.
No adverse effects linked to the device were reported.
There is evidence that rapidly fluctuating magnetic fields that are below the threshold for depolarization can still influence neuronal activity. This, noted the authors, suggests potential cellular mechanisms of action.
Although this is still speculative, Dr. Rohan suggests the device may interact with the nerves in the area of the dendrites where synapses are located.
"The synapses have an electrical function as well as a chemical function, and I suspect that we are interacting with the electrical function in the dendrites."
Because the device seems to provide immediate relief, it might prove useful as a treatment "bridge" in the emergency department, where psychiatric patients may end up in crisis, although the psychiatric community will eventually determine the best application, said Dr. Rohan.
He pointed out that antidepressant medications take several weeks to exert a clinically meaningful improvement in mood and that even ECT requires 2 to 3 treatments per week during a period of up to 4 weeks.
Researchers are now studying the properties of LFMS to determine the optimal frequency, spatial distribution, and timing of the electromagnetic field needed to produce an antidepressant effect.
Dr. Rohan is doing further investigation of the potential mechanisms of the device. He is also participating in a study of 72 patients that is looking at the effect and duration of multiple treatments, the results of which he estimated would be available by the end of next year.
Elsewhere, a multisite study funded by the National Institutes of Health is comparing the device with antidepressant interventions, said Dr. Rohan.
Commenting on the study for Medscape Medical News, Paul E. Holtzheimer, MD, associate professor of psychiatry and surgery, Geisel School of Medicine at Dartmouth, Hanover, New Hampshire, said the study was "great," the results "encouraging," the design "reasonably straightforward," and that he had "no major criticisms" of the research.
"There does seem to be an antidepressant effect; it's not a huge effect, but that's also true for transcranial magnetic stimulation and other approved treatments," said Dr. Holtzheimer. "It warrants further investigation, but in terms of trying to figure out how much of a splash this is going to make, it's too early to say."
The "exciting" aspect of LFMS, said Dr. Holtzheimer, is that it is mechanistically different from TMS in that it is less focal and could be affecting a broader area of the brain involved in mood regulation.
"Mechanistically, it's probably doing something different: it's a similar brain region and a similar idea in terms of altering electrical activity in the brain, but it's different in terms of how focal it is and how much it's altering that activity."
Dr. Holtzheimer warned against being overly enthusiastic about rapid results after using LFMS. He noted that when TMS and deep brain stimulation were first being studied, there were also reports of immediate effects. "Now, we have learned that it's not necessarily related to whether patients get better longer term."
He noted that some patients have an immediate response to drug therapies. "Even though we say that it takes 8 to 12 weeks to have a full effect, some patients get better very quickly."
The same is true for ECT, he added. "We say it takes 9 treatments, but some patients are well within the first 1 or 2 treatments."
McLean Hospital has been awarded patents for the low-field magnetic stimulation treatment and device. Dr. Rohan is listed as an inventor of these patents. He has received consulting fees from Taj Medical, which McLean Hospital approves and limits. Dr. Holtzheimer reports no relevant financial relationships.