LAS VEGAS – Repetitive transcranial magnetic stimulation methods for treatment-resistant depression continue to be refined.
Dr. Alan Schatzberg
“Original studies have relatively low response rates, but we’re seeing better response rates as we figure out the localization, the parameters, the wave form, and how frequently you can give it,” Alan F. Schatzberg, MD, said at an annual psychopharmacology update held by the Nevada Psychiatric Association.
Repetitive transcranial magnetic stimulation (rTMS) involves the application of a magnetic field to a particular area of the brain, typically the dorsal lateral aspect of the prefrontal cortex. “It’s a weaker stimulant than electroconvulsive therapy, but it’s more focused and a lot safer,” said Dr. Schatzberg, professor of psychiatry and behavioral sciences at Stanford (Calif.) University. “It does not require anesthesia. In fact, it does seem to have some antidepressant effects.”
The original trial that applied this technology was conducted in 301 medication-free patients with major depression who had not benefited from prior treatment (Biol Psychiatry. 2007;62[11]:1208-16). Of the 301 patients, 155 received active rTMS, while 146 received sham rTMS. Treatment sessions were conducted five times per week for 4-6 weeks. The primary outcome was the symptom score change as assessed at week 4 with the Montgomery-Åsberg Depression Rating Scale (MADRS). Secondary outcomes included changes on the 17- and 24-item Hamilton Depression Rating Scale (HAMD), and response and remission rates with the MADRS and HAMD.
Response rates were significantly higher with active TMS on all three scales at weeks 4 and 6. Remission rates were approximately twofold higher with active TMS at week 6 and significant on the MADRS and HAMD24 scales (but not the HAMD17 scale). “The response rate for patients receiving active treatment was about 20%, and the remission at 6 weeks was about 18%,” said Dr. Schatzberg, who was an adviser to the study. “It was about twofold higher than in the sham group. It’s not dramatically effective, but it certainly is better than the sham control.” The MADRS score dropped about 6 points in the rTMS group, compared with about 2 points in the sham group, while the HAMD 24 score dropped about 7 points in the rTMS group, compared with about 3.5 points in the sham group.
In a separate, multisite, sham-controlled trial supported by the National Institutes of Health, researchers enrolled 199 antidepressant drug-free patients to determine whether daily left prefrontal rTMS safely and effectively treats major depressive disorder (Arch Gen Psychiatry. 2010;67[5]:507-16). Over the course of 3 weeks, the researchers delivered rTMS to the left prefrontal cortex for 37.5 minutes (3,000 pulses per session) using a figure-eight solid-core coil. Sham rTMS used a similar coil with a metal insert blocking the magnetic field and scalp electrodes that delivered matched somatosensory sensations. The retention rate was 88%, and no device-related serious adverse events were reported. A significantly greater proportion of patients treated with rTMS achieved remission, compared with those in the sham group (15% vs. 5%, respectively; P = .02). The odds of attaining remission were 4.2 times greater with active rTMS than with the sham treatment.
“These are not huge remission and response rates,” Dr. Schatzberg said of the results from this and other studies. “What can we do to start increasing efficacy? One thing you can do is design a better coil. You can alter the site of application, and you can change the pulse frequency and the pulse number. You can also change the brain wave focus. Theta seems to be mostly associated with hippocampal function around memory. Because of that, a number of groups starting giving theta waves.”
In one such study, researchers used accelerated, high-dose intermittent theta burst stimulation (iTBS) to treat highly treatment-resistant depression patients (Brain. 2018;141[3]:e18). The treatment lasted 5 days and consisted of 10 sessions per day, with 50 minutes between each session. “It’s a much more intensive system that delivers about 90,000 pulses,” said Dr. Schatzberg, who directs the Stanford Mood Disorders Center. Most patients remitted, but the durability of therapeutic response was weak, and all patients relapsed within 2 weeks post treatment.
“There’s more work to be done, but rTMS is really a good technology,” he concluded. “I think we will achieve much higher rates of success with this treatment once we push the envelope a little bit.”
Dr. Schatzberg disclosed that he has served a consultant to Alkermes, Avanir, Bracket, Compass, Delpor, Epiodyne, Janssen, Jazz, Lundbeck, McKinsey, Merck, Myriad Genetics, Owl, Neuronetics, Pfizer, Sage, and Sunovion. He has received research funding from Janssen and also holds an ownership interest in Corcept, Dermira, Delpor, Epiodyne, Incyte Genetics, Madrigal, Merck, Owl Analytics, Seattle Genetics, Titan, and Xhale.