Transcranial Magnetic Stimulation Repels Severe Depression


PHILADELPHIA, Nov. 21 -- Transcranial magnetic stimulation significantly reduces acute symptoms of major depression and offers an alternative to conventional therapy, investigators in a multicenter trial have concluded.Patients treated with transcranial magnetic stimulation had almost a twofold higher remission rate at six weeks compared with patients who received sham therapy in the randomized study, John P. O'Reardon, M.D., of the University of Pennsylvania, and colleagues reported in the Dec. 1 issue of Biological Psychiatry.As many as 40% of patients with major depression do not get adequate improvement in symptoms with medication and psychotherapy, the investigators noted. Depression may progress into treatment-resistant illness for which transcranial magnetic stimulation could be useful.
Action Points
Explain to interested patients that transcranial magnetic stimulation may improve depression in patients who have not responded to antidepressant medication.
Emphasize that TMS has not yet been approved for treatment of any psychiatric disorder.
Transcranial magnetic stimulation involves discharge of a time-varying current from an insulated coil placed on the scalp surface. The discharge generates a brief dynamic magnetic field that induces current flow when reaching a conductive medium, such as neural tissue. The current offers the potential to modulate neural circuitry in a therapeutic fashion.
Symptom improvement achieved with the modality was evident as early as four weeks, and it was associated with minimal side effects. The benefits persisted during a taper phase of the study.
"It is worth noting that active transcranial magnetic stimulation subjects continuing through the end of the acute phase and into the taper phase of the study showed persistent and perhaps accumulating benefit in comparison to their continuing counterparts in the sham transcranial magnetic stimulation group," the authors concluded.
Several single-center controlled studies have supported the hypothesis that transcranial magnetic stimulation has antidepressant effects when delivered to the left or right dorsolateral prefrontal cortex. Dr. O'Reardon and colleagues continued the investigation of that hypothesis with a double-blind, multicenter study of 301 medication-free patients with major depression that had been resistant to prior therapy (average of 1.6 prior therapies).

Philip G. Janicak, M.D.Rush University Medical Center, Chicago
The patients were randomized to active or sham transcranial magnetic stimulation administered five times a week for four to six weeks. The primary outcome was the improvement in symptom score at week four on the Montgomery-Asberg Depression Rating Scale (MADRS). Secondary endpoints were change in score on the 17- and 24-item Hamilton Depression Rating Scale (HAMD) and response and remission rates as determined by the MADRS and HAMD.
After correcting for baseline differences in depression severity, investigators found that active transcranial magnetic stimulation significantly improved the mean MADRS score at week four compared with sham treatments (P=0.038). A trend toward more improvement was still evident at six weeks (P=0.052). HAMD-17 and HAMD-24 scores demonstrated significant improvement with active treatment (P=0.006 and P=0.012) at four weeks and at six weeks (P=0.005 and P=0.015).
Response rates at four weeks and six weeks showed significant improvement with active versus sham transcranial magnetic stimulation for the MADRS (P0.05, P0.01), HAMD-17 (P0.05 at both time points), and HAMD-24 (P0.05 for both). Remission rates were significantly higher at six weeks with active treatment (P0.05) and for the HAMD-24 (P0.05).
Putting the transcranial magnetic stimulation results in perspective, Dr. O'Reardon and colleagues noted that the large open-label STAR*D trial of antidepressant medication showed a progressive reduction in the remission rate over time (Am J Psychiatry 2006; 163: 28-40). In contrast, the TMS remission rate by the HAMD-17 increased from 15.5% at six weeks to 22.6% after nine weeks and completion of the taper phase of the study.
"Given that controlled trials generally report somewhat lower clinical response and remission rates than are seen in open-label experience, the results reported here compare favorably to those seen in similarly treatment-resistant patients in the STAR*D reports," the authors noted.
Active transcranial magnetic stimulation was well tolerated, and the most common adverse event was transient scalp discomfort or pain. Fewer than 5% of patients dropped out over adverse events.
Dr. O'Reardon reported receiving grant support from Bristol-Myers Squibb, Cyberonics, Lilly, Magstim, Neuronetics, Pfizer, and Sanofi, consulting with Lilly and Neuronetics, and participating on speakers bureaus for BMS, Cyberonics, and Lilly. The study was supported by Neuronetics.Primary source: Biological PsychiatrySource reference: O'Reardon JP, et al "Efficacy and safety of transcranial magnetic stimulation in the acute treatment of major depression: a multisite randomized controlled trial" Biol Psychiatry 2007; DOI: 10.1016/j.biopsych.2007.01.018.