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

O’Reardon, John P.; Solvason, H. Brent; Janicak, Philip G.; Sampson, Shirlene; Isenberg, Keith E.; Nahas, Ziad; McDonald, William M.; Avery, David; Fitzgerald, Paul B.; Loo, Colleen; Demitrack, Mark A.; George, Mark S.; Sackeim, Harold A.

doi:10.1016/j.biopsych.2007.01.018

« Previous Next »Biological Psychiatry
Volume 62, Issue 11 , Pages 1208-1216, 1 December 2007

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

John P. O’Reardon
- Department of Psychiatry, University of Pennsylvania, Philadelphia
- 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.
H. Brent Solvason
- Department of Psychiatry, Stanford University, Palo Alto, California
Philip G. Janicak
- Department of Psychiatry, Rush University Medical Center, Chicago, Illinois
Shirlene Sampson
- Mayo Clinic College of Medicine, Rochester, Minnesota
Keith E. Isenberg
- Department of Psychiatry, Washington University School of Medicine, St. Louis, Missouri
Ziad Nahas
- Department of Psychiatry, Medical University of South Carolina, Charleston, South Carolina
William M. McDonald
- Department of Psychiatry and Behavioral Sciences, Emory University, Atlanta, Georgia
David Avery
- Department of Psychiatry and Behavioral Sciences, University of Washington School of Medicine, Seattle, Washington
Paul B. Fitzgerald
- Alfred Psychiatry Research Centre, the Alfred and Monash University School of Psychology, Psychiatry and Psychological Medicine, Melbourne, Australia
Colleen Loo
- School of Psychiatry, University of NSW, Sydney, Australia
Mark A. Demitrack
- Neuronetics, Inc., Malvern, Pennsylvania
Mark S. George
- Department of Psychiatry, Medical University of South Carolina, Charleston, South Carolina
Harold A. Sackeim
- Department of Biological Psychiatry, New York State Psychiatric Institute and College of Physicians and Surgeons, Columbia University, New York.

Received 29 September 2006; received in revised form 25 November 2006; accepted 19 January 2007. published online 16 June 2007.

Background

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.

Methods

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.

Results

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.

Conclusions

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