This entire article is available in PDF format to paid subscribers (certain restrictions apply).
If you have not already registered for Full Text Access to The Journal, then visit our registration page.

An Open-Label, Prospective Study of Repetitive Transcranial Magnetic Stimulation (rTMS) in the Long-Term Treatment of Refractory Depression: Reproducibility and Duration of the Antidepressant Effect in Medication-Free Patients

Asli Demirtas-Tatlidede, M.D.; Dawn Mechanic-Hamilton, B.A.; Daniel Z. Press, M.D.; Chester Pearlman, M.D.; William M. Stern, M.A., M.B.B.S.; Mark Thall, M.D.; and Alvaro Pascual-Leone, M.D., Ph.D.

Objective: Several studies have assessed the acute antidepressant effects of repetitive transcranial magnetic stimulation (rTMS), and many have revealed positive results. However, the impact of rTMS throughout the long course of major depressive disorder (MDD) and the efficacy of rTMS in the treatment of depressive relapses still remain to be elucidated.

Method: Sixteen medication-free patients with refractory MDD (diagnosed according to DSM-IV) who initially had clinically significant antidepressant responses to a 10-day course of 10-Hz rTMS were consecutively admitted to the protocol from 1997 to 2001 and were followed for 4 years. The cohort was studied during a total of 64 episodes of depressive relapse. Severity of depression was evaluated with the Hamilton Rating Scale for Depression (HAM-D) and the Beck Depression Inventory (BDI) prior to and after completion of each rTMS treatment course. Clinically significant response was defined as a reduction in HAM-D score of at least 50%. Safety was assessed by serial neurologic examinations and neuropsychological evaluations.

Results: Approximately one half of the patients individually sustained a clinically significant response to the repeated courses of rTMS; the mean ± SD decrease in HAM-D scores was 64.8% ± 12.6% (p < .0001), and, in BDI scores, 60.4% ± 20.6% (p < .0001). Despite the lack of adjuvant antidepressant medication, the mean interval between treatment courses was approximately 5 months, and the medication-free period ranged from 26 to 43 months. Transcranial magnetic stimulation was well tolerated, and evaluations regarding the safety of the repeated applications of rTMS revealed no findings of concern.

Conclusions: Repeated rTMS applications have demonstrated a reproducible antidepressant effect in patients with refractory depression who initially showed a clinically significant benefit. The duration of effect varied across patients, but benefits were sustained for a mean of nearly 5 months. Further studies with larger cohorts will be useful in determining the long-term effectiveness of rTMS maintenance therapy.


(J Clin Psychiatry 2008;69:930-934. Online Ahead of Print May 20, 2008.)

Received May 26, 2007; accepted Oct. 28, 2007. From the Berenson-Allen Center for Noninvasive Brain Stimulation, Harvard Medical School, and the Department of Neurology, Behavioral Neurology Unit, Beth Israel Deaconess Medical Center, Boston, Mass.

This study was supported by the National Institute of Mental Health (RO1MH60734, RO1MH57980, K24 RR018875), the National Alliance for Research in Schizophrenia and Depression, the Stanley Vada Foundation, and the General Clinical Research Center at Beth Israel Deaconess Medical Center (NCRR MO1 RR01032).

The authors report no additional financial or other relationships relevant to the subject of this article.

Corresponding author and reprints: Alvaro Pascual-Leone, M.D., Ph.D., Berenson-Allen Center for Noninvasive Brain Stimulation, Beth Israel Deaconess Medical Center, 330 Brookline Ave., KS-452, Boston, MA 02215 (e-mail: