Electromagnetic Stimulation Shows Promise For Treatment-Resistant Depression

Transcranial Magnetic Stimulation (TMS) is a non-invasive technique that uses a powerful electro-magnet placed on the scalp of a person to alter brain activity. Originally developed as a diagnostic tool for mapping brain function, TMS appears promising as a treatment for a variety of complex neuropsychiatric conditions, particularly major depression.

TMS induces an electromagnetic current in the underlying cortical neurons, which may explain its therapeutic effects. Repetitive TMS, using varying frequencies and intensities, can increase or decrease excitability in the cortical area directly targeted by the stimulation. Recent studies combining TMS and neuroimaging techniques, such as magnetic resonance imaging, demonstrate that the effects of TMS are not limited to the cortex but spread to functionally related subcortical structures. This finding provides a basis for using TMS to treat the pathologic neural activity that may underlie neuropsychiatric illness.

At this time, repeated transcranial magnetic stimulation (rTMS) is still experimental and actual clinical use will require much more research.

Clinical Studies: Pilot studies of TMS have reported improvement in major depression, mania, post traumatic stress disorder (PTSD), Parkinson's disease and obsessive compulsive disorder. Major depression has been the most extensively studied of these illnesses, primarily because substantial evidence suggests that the left prefrontal cortex becomes less active during clinical depression and because the prefrontal cortex is easily accessible to TMS stimulation.

Initial case reports and open label trials reported by several groups support the use of TMS as an antidepressant treatment. These promising early results have led to a limited number of controlled trials.

Kolbinger and colleagues reported a semi-blinded study in which 15 patients were divided into a placebo group and two treatment groups that received high and low frequency TMS. Using the Hamilton Depression Rating Scale (HDRS), results indicated no change in the placebo group and a reduction of symptoms in the treatment groups; however, the changes in the treatment groups did not reach statistical significance.

A few studies have looked at patients refractory (resistant) to traditional treatments. Pascual-Leone and colleagues reported significant antidepressant effects in 11 out of 17 medication-resistant depressed patients treated with TMS to the left dorsolateral prefrontal cortex for five days. George and colleagues treated 12 medication-resistant patients with TMS for two weeks and with placebo treatment for two weeks, using a cross-over design. The researchers found an average decrease in HDRS of five points during active treatment and an average decrease of three points during placebo treatment. Similarly, Figiel and colleagues reported that 21 out of 50 patients with refractory depression had an antidepressant response to TMS. Their data also suggest that younger patients may respond to TMS better than elderly patients.


Grisaru and colleagues also studied the use of TMS in treating acute mania. They randomly assigned patients to stimulation of either the right or left prefrontal cortex for 10 consecutive days. Patients receiving right-sided stimulation showed a statistically significant decrease in manic symptoms at the end of the trial.

To date, there have been two published reports on the use of TMS in PTSD patients. Grisaru and colleagues applied TMS (one session of 30 pulses) to 10 patients and reported improvement in avoidance, anxiety and somatization symptoms, as well as general clinical improvement as measured by the Clinical Global Impression Scale. McCann and colleagues reported on two PTSD patients treated with low frequency TMS who showed a reduction in symptoms during treatment but whose symptoms returned within one month after ending treatment.

Initial reports using TMS for Parkinson's disease are very limited and focus on the use of TMS as a probe of cortical function rather than a treatment. Pascual-Leone and colleagues demonstrated decreased reaction times, as well as decreased movement time, in Parkinson patients treated with TMS.

Side Effects: To date, the most serious side effect of TMS has been the induction of grand mal seizures in seven subjects. Five of the seizures occurred prior to the introduction of safety guidelines in 1993. These guidelines subsequently were revised in 1996. Other reported side effects include headache. In addition, 3 percent of patients reported a nonspecific sense of discomfort experienced during treatment that usually resolved after the first few treatment sessions.

Conclusions: TMS appears to be a promising potential tool for modulating the activity of cortical neurons. Until additional convincing evidence of its clinical efficacy and safety is available, TMS remains an experimental intervention. Because it is very difficult to blind the placebo condition fully and because depression is an illness with a high placebo response rate, the few controlled studies now in the literature must be interpreted cautiously. Nonetheless, results of these initial studies are encouraging. Additional studies need to be performed to determine the optimal use of TMS and whether the technique ultimately will merit inclusion in the broadening array of treatments for neuropsychiatric disorders.

Additional Reading
Pascual-Leone A, Rubio B; Pallardo F; Catala, MD. Rapid-rate transcranial magnetic stimulation of left dorsolateral prefrontal cortex in drug-resistant depression. Lancet 1996; 348:233-237.

George, MS; Wasserman, EM; Kimbrell, TA; Little, JT; Williams, WE; Danielson, AL; Greenberg, BD; Hallett, M: Post, RM. Mood improvement following daily left prefrontal repetitive transcranial magnetic stimulation in patients with depression: a placebo-controlled cross-over trial. Am J Psychiatry 1997; 154:1752-1756.

Wasserman, EM. Risk and safety of repetitive transcranial magnetic stimulation: report and suggested guidelines from the International Workshop on the Safety of Repetitive Transcranial Magnetic Stimulation, June 5-7, 1996. Electroencephalogr Clin Neurophysiol 1998; 108:1-16.

Figiel, GS; Epstein, C; McDonald, WM; Amazon-Leece, J; Figiel, L; Saldiva, A; Glover, S. The use of rapid-rate transcranial magnetic stimulation (rTMS) in refractory depressed patients. J Neuropsychiatry Clin Neurosci 1998; 10:20-25.

This article was submitted by Michael Henry, MD, director of McLean Hospital's ECT Service; A. Pascual-Leone, MD, PhD, director of the Laboratory for Magnetic Brain Stimulation at Beth Israel Deaconess Medical Center; and Jonathan Cole, MD, director of McLean Hospital's Psychopharmacology Research Program, senior consultant to McLean's Depression and Anxiety Disorders Outpatient Service and professor of psychiatry at Harvard Medical School.