UC Berkeley Press Release

Patients with a major depressive episode responding to treatment with repetitive transcranial magnetic stimulation (rTMS) are resistant to the effects of rapid tryptophan depletion

John P. O'Reardon, M.D. 1 * , Pilar Cristancho, M.D. 1 , Pramod Pilania, M.D. 2 , Kiran B. Bapatla, M.D., M.P.H. 1 , Shaokun Chuai, M.Sc. 3 , Andrew D. Peshek, M.D. 1

1 Laboratory for Transcranial Magnetic Stimulation, University of Pennsylvania, Philadelphia, Pennsylvania
2 Department of Psychiatry, Temple University, Philadelphia, Pennsylvania
3 Center for Clinical Epidemiology and Biostatistics, University of Pennsylvania, Philadelphia, Pennsylvania

email: John P. O'Reardon ( oreardon@mail.med.upenn.edu )

* Correspondence to John P. O'Reardon, Laboratory for Transcranial Magnetic Stimulation, University of Pennsylvania, Suite 4005, 3535 Market St., Philadelphia, PA 19104

Depression and Anxiety Volume 24, Issue 8 , Pages 537 – 544 Published Online: 27 Nov 2006 © 2006 Wiley-Liss, Inc.



rTMS • major depression • serotonin • tryptophan depletion


Repetitive transcranial magnetic stimulation (rTMS) appears to be efficacious in the treatment of major depression based on the results of controlled studies, but little is known about its antidepressant mechanism of action. Mood sensitivity following rapid tryptophan depletion (RTD) has been demonstrated in depressed patients responding to SSRI antidepressants and phototherapy, but not in responders to electroconvulsive therapy (ECT). We sought to study the effects of RTD in patients with major depression responding to a course of treatment with rTMS. Twelve subjects treated successfully with rTMS monotherapy underwent both RTD and sham depletion in a double-blind crossover design. Depressive symptoms were assessed using both a modified Hamilton Depression Rating Scale (HDRS) and Beck Depression Inventory (BDI). The differential change in depression scores across the procedures was compared. No significant difference in mood symptoms was noted between RTD and the sham-depletion procedure on either continuous measures of depression, or in the proportions of subjects that met predefined criteria for a significant degree of mood worsening. Responders to rTMS are resistant to the mood perturbing effects of RTD. This suggests that rTMS does not depend on the central availability of serotonin to exert antidepressant effects in major depression. Depression Anxiety 24:537-544, 2007. © 2006 Wiley-Liss, Inc.

Received: 6 April 2006; Revised: 30 June 2006; Accepted: 5 July 2006