December 18, 2007 — A large, randomized controlled trial finds that transcranial magnetic stimulation (TMS) is safe and effective for treatment-resistant major depression. Response and remission were better in patients who received 4 to 6 weeks of treatment with active TMS than with sham TMS.
The study is published in the December 1 issue of Biological Psychiatry.
"These results indicate that TMS provides a novel and attractive treatment option for patients with major depression who have not responded to conventional antidepressant medications," said lead author John P. O'Reardon, MD, from the University of Pennsylvania, in Philadelphia, in a press release issued by Rush University Medical Center, in Chicago, Illinois, one of the 23 study sites.
The study was conducted by Neuronetics (Malvern, Pennsylvania), under an investigational device exemption from the US Food and Drug Administration.
"This study provides new support for the efficacy of TMS as a stand-alone treatment for depression," said John H. Krystal, MD, editor of Biological Psychiatry, who was not part of the study. The findings could be especially important for patients who do not tolerate antidepressant medications or who have not benefited from alternative treatments, he added.
Is TMS Safe, Effective?
An estimated 20% to 40% of patients with major depressive disorder do not benefit sufficiently from interventions with antidepressants and psychotherapy, and TMS has been proposed as an alternative treatment, the authors write. Small, previous studies have largely shown that, compared with sham treatment, slow stimulation over the right dorsolateral prefrontal cortex or fast stimulation over the left dorsolateral prefrontal cortex results in greater antidepressant effects than does sham stimulation, but some reports showed no clear-cut benefit from TMS.
The group conducted a large randomized controlled trial to determine whether TMS over the left dorsolateral prefrontal cortex is effective and safe in the acute treatment of major depression. They used a longer course of treatment than previous studies and the highest feasible dose consistent with safety guidelines.
The study was conducted at 20 sites in the United States, 2 sites in Australia, and 1 site in Canada. Eligible patients had major depression and had not benefited from 1 to 4 prior trials of antidepressant therapies.
A total of 301 patients (about 50% women; average age close to 50 years) were randomized to either active TMS or sham TMS with a device that had a magnetic shield.
TMS is a noninvasive technique that excites neurons in the brain by magnetic impulses introduced through the scalp. The TMS treatment in this study consisted of 3000 magnetic pulses per session given 5 days a week for 4 to 6 weeks. Treatment was done using a Neuronetics device at a repetition rate of 10 pulses/sec and at an intensity of 120% of the patient's resting motor threshold.
The primary efficacy outcome was the change the Montgomery-Asberg Depression Rating Scale (MADRS) symptom score at week 4. Secondary outcomes included changes in the 17- and 24-item Hamilton Depression Rating Scale (HAMD) and in response and remission rates.
"TMS Offers New Hope"
At week 4, after baseline score imbalance was corrected for, MADRS mean symptom scores were significantly better in patients treated with active TMS vs sham TMS. Mean HAMD17 and HAMD24 symptom scores at weeks 4 and 6 were also better with active treatment.
At 6 weeks, patients in the active-TMS group were about twice as likely to have achieved remission compared with those in the sham-TMS group (MADRS: 14.2% vs 5.2%; HAMD17: 15.5% vs 7.1%; HAMD24: 17.4% vs 8.2%).
TMS was safe and well tolerated. There was a higher incidence of scalp discomfort and pain with active treatment than with sham, but these events were generally mild or moderate, and the incidence diminished rapidly after week 1.
The dropout rate from active TMS was 7.7% at 4 weeks and discontinuation due to adverse effects was 4.5%.
"The patients included had an average of 1.6 failed adequate trials in the current episode of major depression, and nearly half had failed to benefit from 2 or more treatments," the group writes, adding that their findings compare favorably to those seen in similarly treatment-resistant patients in the Sequenced Treatment Alternatives to Relieve Depression (STAR*D) reports.
"There is a great need to develop new effective treatments for patients, especially those not benefiting from first-line interventions," said Dr. O'Reardon. "The results of this study indicate that TMS offers patients new hope in this regard."
The clinical trial was supported by a grant from Neuronetics Inc. Dr. O'Reardon has received grant support from Bristol-Myers Squibb, Cyberonics, Lilly, Magstim, Neuronetics, Pfizer, and Sanofi. He has acted as a consultant for Lilly and Neuronetics and is a member of the speakers' bureaus for Bristol-Myers Squibb, Cyberonics, and Lilly. The financial disclosures of the other authors are listed in the paper.
Biol Psychiatry. 2007;62:1208-1216. Abstract
Medscape Medical News © 2007 Medscape
Cite this: Marlene Busko. Transcranial Magnetic Stimulation Effective for Depression in Large Trial - Medscape - Dec 18, 2007.