V E TE R AN S AFFAI R S & M I LITARY M E D I CI N E O UTLO O K
NIH IMAGE
Illustration of transcranial magnetic stimulation, or TMS. Studies suggest that TMS is effective for at least some patients suffering from depression.
treatment-resistant depression, published in June 2018, demonstrated a similar rate of remission, 40 percent, among patients who received active stimulation – but 37 percent of those who received a “sham” treatment, or procedural placebo, also reported remission. “In most of the prior TMS studies, the sham remission rate is down around 5 to maybe 10 percent,” said Holtzheimer. “To have a study with such a high [sham] remission rate suggests something about the study, or something about the patients being enrolled, is very different from all of the probably close to a thousand patients enrolled in studies prior to that.” Holtzheimer has collaborated with Dr. Helen Mayberg, a neurologist at Emory University, in analyzing a brain stimulation technique Mayberg pioneered to target the subcallosal cingulate region of the brain. Often
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known simply as Area 25, this region is rich in serotonin transporters and is known to be metabolically overactive in patients with treatmentresistant depression. Mayberg’s intervention, deep brain stimulation (DBS), involves the surgical insertion of a battery-powered electrode directly into this region of the brain. The amount and frequency of pulses delivered by the device are fine tuned after the surgery. According to Mayberg, many of the patients who received the first DBS implants have lived depression-free since the first operations were performed more than a dozen years ago, while other patients with depression appear not to be helped by DBS. So far nobody, including Mayberg nor Holtzheimer, understands why, and the FDA hasn’t yet approved it for the treatment of depression. Holtzheimer’s most recent study of the procedure,
published in Lancet Psychiatry in 2017, demonstrated that it was a safe and feasible procedure – and that while it was only slightly more effective than sham treatments after a period of six months, patients who were treated over a period of two years did well compared to subjects of earlier studies. “There’s still the possibility that longerterm stimulation could be effective in highly resistant patients,” Holtzheimer said, “and the patients who get better didn’t seem to relapse. They tended to stay better over time.” More studies are needed, he concluded, to investigate factors such as electrode placement and other clinical features. “We’re hoping we can do another study, designed somewhat differently,” he said, “to better show that active stimulation works and evaluate longerterm effects of the treatment. The flipside of this is that in patients where DBS seems to work – and we did this in our first study at Emory – when you turn off the stimulation, almost 100 percent of the patients get depressed again … and then if you turn it back on, they get less depressed.” More data are coming out from patients studied at both Emory and Dartmouth, Holtzheimer said, and more studies of the procedure are being planned. In the last few years, early studies of DBS in the regions of the brain associated with fear and anxiety – including a 2015 study of veterans at the VA Greater Los Angeles Healthcare System – have shown the procedure to be safe and effective in treating PTSD. Activation of the brain’s neural circuits represents a new frontier in treating depression and other psychiatric conditions, and Holtzheimer and other VA investigators are at the vanguard of explorers hoping to unlock their secrets and put them to work for American veterans.
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