UC Berkeley Press Release

Efficacy and Safety of Transcranial Magnetic Stimulation in the Acute Treatment of Major Depression: A Multisite Randomized Controlled Trial

John P. O'Reardon a ,, H. Brent Solvason b , Philip G. Janicak c , Shirlene Sampson d , Keith E. Isenberg e , Ziad Nahas j , William M. McDonald f , David Avery g , Paul B. Fitzgerald h , Colleen Loo i , Mark A. Demitrack k , Mark S. George j and Harold A. Sackeim l
a Department of Psychiatry, University of Pennsylvania, Philadelphia
b Department of Psychiatry, Stanford University, Palo Alto, California
c Department of Psychiatry, Rush University Medical Center, Chicago, Illinois
d Mayo Clinic College of Medicine, Rochester, Minnesota
e Department of Psychiatry, Washington University School of Medicine, St. Louis, Missouri
f Department of Psychiatry and Behavioral Sciences, Emory University, Atlanta, Georgia
g Department of Psychiatry and Behavioral Sciences, University of Washington School of Medicine, Seattle, Washington
h Alfred Psychiatry Research Centre, the Alfred and Monash University School of Psychology, Psychiatry and Psychological Medicine, Melbourne, Australia
i School of Psychiatry, University of NSW, Sydney, Australia
j Department of Psychiatry, Medical University of South Carolina, Charleston, South Carolina
k Neuronetics, Inc., Malvern, Pennsylvania
l Department of Biological Psychiatry, New York State Psychiatric Institute and College of Physicians and Surgeons, Columbia University, New York.
Received 29 September 2006;  revised 25 November 2006;  accepted 19 January 2007.  Available online 14 June 2007.


We tested whether transcranial magnetic stimulation (TMS) over the left dorsolateral prefrontal cortex (DLPFC) is effective and safe in the acute treatment of major depression.


In a double-blind, multisite study, 301 medication-free patients with major depression who had not benefited from prior treatment were randomized to active ( n = 155) or sham TMS ( n = 146) conditions. Sessions were conducted five times per week with TMS at 10 pulses/sec, 120% of motor threshold, 3000 pulses/session, for 4–6 weeks. Primary outcome was the symptom score change as assessed at week 4 with the Montgomery–Asberg 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.


Active TMS was significantly superior to sham TMS on the MADRS at week 4 (with a post hoc correction for inequality in symptom severity between groups at baseline), as well as on the HAMD17 and HAMD24 scales at weeks 4 and 6. 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). Active TMS was well tolerated with a low dropout rate for adverse events (4.5%) that were generally mild and limited to transient scalp discomfort or pain.


Transcranial magnetic stimulation was effective in treating major depression with minimal side effects reported. It offers clinicians a novel alternative for the treatment of this disorder.

Key Words: Clinical trial; efficacy; major depression; safety; TMS

Address reprint requests to John P. O'Reardon, M.D., Laboratory for Transcranial Magnetic Stimulation, University of Pennsylvania, 3535 Market Street, Suite 4005, Philadelphia, PA 19014.

Biological Psychiatry
Volume 62, Issue 11 , 1 December 2007, Pages 1208-1216
Depression: New Perspectives on Treatment and Etiology