Monday, May 03, 2010

Brain-Stimulation Method Appears to Help Induce Remission in Some Patients With Depression

The future of psychiatric medicine might be in brain implants, at least for some forms of mental illness. It seems that these devices may offer more direct and pin-pointed treatments by directly hitting the brain area involved in, for example, major depression that does not respond to therapy or medications.

This release is from the ARCHIVES OF GENERAL PSYCHIATRY.
Brain-Stimulation Method Appears to Help Induce Remission in Some Patients With Depression

CHICAGO—Daily transcranial magnetic stimulation—an intervention that uses magnetic currents to activate certain brain areas—appears to help induce remission in patients with treatment-resistant depression, according to a report in the May issue of Archives of General Psychiatry, one of the JAMA/Archives journals.

Major depression is common, disabling and expensive, and more effective treatments are needed, according to background information in the article. Some patients experience little or no improvement after medication, psychotherapy or both. Transcranial magnetic stimulation has shown potential as a depression treatment, but there is concern regarding the quality of existing research.

Mark S. George, M.D., of the Medical University of South Carolina, Charleston, and colleagues conducted a randomized controlled trial of repetitive transcranial magnetic stimulation among 190 patients with depression who were not taking medication. Of these, 92 were randomly assigned to receive the intervention, which involved stimulating the left prefrontal cortex with an electromagnetic coil for 37.5 minutes daily for three weeks. The other 98 received a sham treatment that mimicked the sensory experience of stimulation using a similar coil and scalp electrodes but with the magnetic field blocked.

A total of 90 percent of patients in the sham group and 86 percent in the treatment group completed the study. Among these, depression remitted in 14.1 percent in the transcranial magnetic stimulation group, compared with 5.1 percent in the sham group. The odds of achieving remission were 4.2 times greater in the active treatment group.

"One of the most important aspects of the study was ensuring that no one who knew the randomization status of the patient ever came in contact with the patient or interacted with the data," the authors write. "We developed a new active sham transcranial magnetic stimulation system that simulated the repetitive transcranial magnetic stimulation somatosensory experience and effectively masked the patients, the raters and, to a large extent, the treaters." At the end of the treatment phase, patients, treaters and clinical raters were asked to guess whether they were in the active or treatment group. Only treaters were able to guess at a rate more accurate than chance, and they were not very confident of their responses.

The researchers calculated that for every 12 patients treated with transcranial magnetic stimulation, one would remit from depression. Most remissions occurred among individuals with low antidepressant treatment resistance.

"The results of this study suggest that prefrontal repetitive transcranial magnetic stimulation is a monotherapy with few adverse effects and significant antidepressant effects for unipolar depressed patients who do not respond to medications or who cannot tolerate them," the authors conclude.

(Arch Gen Psychiatry. 2010;67[5]:507-516).

Editor's Note: This study was supported by the National Institute of Mental Health as the Optimization of TMS for the Treatment of Depression Study. Please see the article for additional information, including other authors, author contributions and affiliations, financial disclosures, funding and support, etc.

Media Advisory: To contact Mark S. George, M.D., call Megan Fink at 843-792-5172 or e-mail
For those who would like more information on the study, here is the abstract:
Daily Left Prefrontal Transcranial Magnetic Stimulation Therapy for Major Depressive Disorder

A Sham-Controlled Randomized Trial

Mark S. George, MD; Sarah H. Lisanby, MD; David Avery, MD; William M. McDonald, MD; Valerie Durkalski, PhD; Martina Pavlicova, PhD; Berry Anderson, PhD, RN; Ziad Nahas, MD; Peter Bulow, MD; Paul Zarkowski, MD; Paul E. Holtzheimer III, MD; Theresa Schwartz, MS; Harold A. Sackeim, PhD

Arch Gen Psychiatry. 2010;67(5):507-516.

Context Daily left prefrontal repetitive transcranial magnetic stimulation (rTMS) has been studied as a potential treatment for depression, but previous work had mixed outcomes and did not adequately mask sham conditions.

Objective To test whether daily left prefrontal rTMS safely and effectively treats major depressive disorder.

Design Prospective, multisite, randomized, active sham-controlled (1:1 randomization), duration-adaptive design with 3 weeks of daily weekday treatment (fixed-dose phase) followed by continued blinded treatment for up to another 3 weeks in improvers.

Setting Four US university hospital clinics.

Patients Approximately 860 outpatients were screened, yielding 199 antidepressant drug–free patients with unipolar nonpsychotic major depressive disorder.

Intervention We delivered rTMS to the left prefrontal cortex at 120% motor threshold (10 Hz, 4-second train duration, and 26-second intertrain interval) for 37.5 minutes (3000 pulses per session) using a figure-eight solid-core coil. Sham rTMS used a similar coil with a metal insert blocking the magnetic field and scalp electrodes that delivered matched somatosensory sensations.

Main Outcome Measure In the intention-to-treat sample (n = 190), remission rates were compared for the 2 treatment arms using logistic regression and controlling for site, treatment resistance, age, and duration of the current depressive episode.

Results Patients, treaters, and raters were effectively masked. Minimal adverse effects did not differ by treatment arm, with an 88% retention rate (90% sham and 86% active). Primary efficacy analysis revealed a significant effect of treatment on the proportion of remitters (14.1% active rTMS and 5.1% sham) (P = .02). The odds of attaining remission were 4.2 times greater with active rTMS than with sham (95% confidence interval, 1.32-13.24). The number needed to treat was 12. Most remitters had low antidepressant treatment resistance. Almost 30% of patients remitted in the open-label follow-up (30.2% originally active and 29.6% sham).

Conclusion Daily left prefrontal rTMS as monotherapy produced statistically significant and clinically meaningful antidepressant therapeutic effects greater than sham.

Trial Registration Identifier: NCT00149838

Author Affiliations: Brain Stimulation Division, Department of Psychiatry (Drs George, Anderson, and Nahas), and Department of Biometry (Dr Durkalski), Medical University of South Carolina, Charleston; Ralph H. Johnson Veterans Affairs Medical Center, Charleston (Dr George); the Division of Brain Stimulation and Therapeutic Modulation, Columbia University/New York State Psychiatric Institute, New York, New York (Drs Lisanby and Bulow); Department of Psychiatry, University of Washington, Seattle (Drs Avery and Zarkowski); Department of Psychiatry, Emory University, Atlanta, Georgia (Drs McDonald and Holtzheimer); and Departments of Biostatistics (Drs Pavlicova and Ms Schwartz) and Psychiatry (Dr Sackeim), Columbia University College of Physicians and Surgeons, New York.

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