Article Text

Slow, repetitive transcranial magnetic stimulation was effective for major depression

Statistics from

Request Permissions

If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.

Klein E, Kreinin I, Chistyakov A, et al. Therapeutic efficacy of right prefrontal slow repetitive transcranial magnetic stimulation in major depression. A double-blind controlled study. Arch Gen Psychiatry. 1999 Apr; 56:315-20.


In patients with major depression, is slow, repetitive transcranial magnetic stimulation (rTMS) effective for relieving depressive symptoms?


2-week randomised, double-blind, placebo-controlled trial.


{Psychiatric department of a general hospital}* in Israel.


70 patients (mean age 59 y, 76% women) who had major depression according to the Diagnostic and Statistical Manual of Mental Disorders, 4th edition; were right handed; had normal neurological and general physical examination results; did not have a history of major brain trauma, seizure disorder, or substance abuse; and were not medication resistant. Follow-up was 96%.


Patients were allocated to rTMS (n = 36) or sham rTMS (n = 34). In rTMS, a magnetic stimulator (Cadwell Inc., Kennewick, WA, USA) with a 9-cm external diameter circular coil was placed over the right prefrontal area 6 cm anterior to the scalp position at which the motor threshold was determined. In sham rTMS, the stimulation coil was placed perpendicular to the scalp without direct contact. 10 daily sessions were given over 2 weeks.

Main outcome measures

Severity of depression (assessed with the Hamilton Depression Rating Scale [HDRS] and the Montgomery-Asberg Depression Rating Scale [MADRS]) at baseline, after 1 week of treatment, and at 24 hours after the last treatment session.

Main results

More patients in the rTMS group than in the sham-rTMS group had 50% reduction in HDRS or MADRS scores (P < 0.05) and had a final HDRS score £ 10 (P < 0.02) (Table). No serious adverse effects were reported in either group.


In patients with major depression, slow, repetitive transcranial magnetic stimulation led to a reduction in depressive symptoms.

Source of funding: Stanley Foundation.

For correspondence: Dr. E. Klein, Department of Psychiatry, Rambam Medical Center, Efron Street, Bat-Galim, Haifa 31096, Israel. FAX 972-4-8514285.

*Information supplied by author.

Abstract and Commentary also published in Evidence-Based Mental Health. 1999 Nov.

Slow, repetitive transcranial magnetic stimulation (rTMS) vs sham rTMS for major depression

Outcomes at 2 wk rTMS Sham rTMS RBI (95% CI) NNT (CI)

50% reduction in HDRS 49% 25% 94% (1 to 293) 5 (3 to 466)

or MADRS scores

HDRS score £ 10 46% 19% 144% (15 to 450) 4 (3 to 23)

HDRS = Hamilton Depression Rating Scale; MADRS = Montgomery-Asberg Depression Rating Scale. Other abbreviations defined in Glossary; RBI, NNT, and CI calculated from data in article.


Rapid rTMS stimulates the cerebral cortex by using magnetic fields generated in an electrical coil. Applied to appropriate brain areas, rTMS can influence cognitive function and perhaps mood in healthy persons. The abnormalities in prefrontal perfusion found in some depressed patients have led to therapeutic trials of rTMS in major depression.

Klein and colleagues found clinically significant antidepressant effects with low- frequency rTMS applied to the right prefrontal area. This study has substantial methodological differences from other positive controlled studies of rTMS in terms of the stimuli used, their site of application, and the coil used to deliver them (1). Antidepressant effects of rTMS raise the tan-talising prospect that it may be possible to replace electroconvulsive therapy (ECT) with a treatment that does not require anaesthesia or cause fits or cognitive impairment. Unlike most patients treated with ECT, however, patients in this study were not medication resistant, and concomitant medication may have influenced the therapeutic response to rTMS.

More work is required to define the most appropriate stimulus parameters and placement for rTMS in the treatment of depression. In addition, a more convincing placebo treatment than sham application needs to be devised. The failure of some studies to replicate specific antidepressant effects of rTMS (1, 2) suggests that this is not a trivial issue.

Philip J. Cowen, MD

University of Oxford

Oxford, England, UK


1. George MS, Lisanby SH, Sackeim HA. Transcranial magnetic stimulation: applications in neuropsychiatry. Arch Gen Psychiatry. 1999;56:300-11.

2. Loo C, Mitchell P, Sachdev P, et al. Double-blind controlled investigation of transcranial magnetic stimulation for the treatment of resistant major depression. Am J Psychiatry. 1999;56:946-8.