May 19, 2010

Daily left prefrontal transcranial magnetic stimulation therapy for major depressive disorder: a sham-controlled randomized trial

PMID: 20439832

AUTHORS: Mark S George, Sarah H Lisanby, David Avery, William M McDonald, Valerie Durkalski, Martina Pavlicova, Berry Anderson, Ziad Nahas, Peter Bulow, Paul Zarkowski, Paul E Holtzheimer, Theresa Schwartz, Harold A Sackeim

AFFILIATION: Brain Stimulation Division, Department of Psychiatry, Medical University of South Carolina, Charleston, SC 29425, USA.

REFERENCE: Arch Gen Psychiatry 2010 May 67(5):507-16

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. TRIAL REGISTRATION: Identifier: NCT00149838.