transcranial magnetic stimulation (rTMS) is a treatment for
major depression. It was approved ( href="http://www.accessdata.fda.gov/cdrh_docs/pdf8/K083538.pdf">PDF)
by the FDA in 2008. However, it has remained somewhat of a niche
treatment. Some providers remain href="http://www.shockmd.com/2008/10/17/transcranial-magnetic-stimulation-gains-approval-of-the-fda-for-depression/">unimpressed
by studies of efficacy. One problem is that most of the studies
have been sponsored by the industry. Often, the studies have used
So now there is a published study, sponsored by the NIH, that used a
good double-blind method. It used a sham procedure that mimics
the sensation of active treatment, while blocking the magnetic
field. It was a multicenter study that included 190
patients. The conclusion: “Daily left prefrontal rTMS as
monotherapy produced statistically
significant and clinically meaningful antidepressant therapeutic
effects greater than sham.” Sounds good, right?
Left Prefrontal Transcranial Magnetic Stimulation Therapy for Major
A Sham-Controlled Randomized Trial
Arch Gen Psychiatry. 2010;67(5):507-516.
Context Daily left prefrontal repetitive transcranial
magnetic stimulation (rTMS) has been studied as a potential treatment
for depression, but previous work had mixed outcomes and did not
adequately mask sham conditions.
Objective To test whether daily left prefrontal rTMS
safely and effectively treats major depressive disorder.
Design Prospective, multisite, randomized, active
sham-controlled (1:1 randomization), duration-adaptive design with 3
weeks of daily weekday treatment (fixed-dose phase) followed by
continued blinded treatment for up to another 3 weeks in improvers.
Setting Four US university hospital clinics.
Patients Approximately 860 outpatients were screened,
yielding 199 antidepressant drug-free patients with unipolar
nonpsychotic major depressive disorder.
Intervention We delivered rTMS to the left prefrontal
cortex at 120% motor threshold (10 Hz, 4-second train duration, and
26-second intertrain interval) for 37.5 minutes (3000 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.
Main Outcome Measure In the intention-to-treat sample (n
= 190), remission rates were compared for the 2 treatment arms using
logistic regression and controlling for site, treatment resistance,
age, and duration of the current depressive episode.
Results Patients, treaters, and raters were effectively
masked. Minimal adverse effects did not differ by treatment arm, with
an 88% retention rate (90% sham and 86% active). Primary efficacy
analysis revealed a significant effect of treatment on the proportion
of remitters (14.1% active rTMS and 5.1% sham) (P = .02). The odds of
attaining remission were 4.2 times greater with active rTMS than with
sham (95% confidence interval, 1.32-13.24). The number needed to treat
was 12. Most remitters had low antidepressant treatment resistance.
Almost 30% of patients remitted in the open-label follow-up (30.2%
originally active and 29.6% sham).
Conclusion Daily left prefrontal rTMS as monotherapy
produced statistically significant and clinically meaningful
antidepressant therapeutic effects greater than sham.
So yes, the conclusion sounds good. The study was done carefully,
using acceptable methodology. Skeptics, however, may find reason
to cast doubt: although the study was funded by an impartial agency,
some of the authors do have industry connections, for href="http://www.medscape.com/viewarticle/721164?src=mpnews&spon=12&uac=27368BZ">example:
Dr. George reports receiving research grants in the past 5
years from Brainsway, Cephos, Force Protection, GlaxoSmithKline, and
Jazz Pharmaceuticals. He has been an unpaid adviser to Brainsonix,
Neostim, Neosync, and Neuronetics Inc (because they make products
related to TMS) and a paid adviser to Cyberonics, Jazz, Neuropace, and
Puretech ventures. The full amount of his advisory income has never
been more than 10% of his university salary. The Medical University of
South Carolina has 2 patent applications in Dr George’s name on
combining TMS with magnetic resonance imaging.
This sort of connection is not unusual, but it is wise to not
completely ignore it when interpreting the study.
How good were the results? Active treatment was associated with a
remission rate of 14.1%, compared to 5.1% in the sham-treatment group.
This is not a startlingly great remission rate. However,
it is a lot better than doing nothing.