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Transcranial Magnetic Stimulation Offers New Options for Treatment-Refractory Depression

New York (Nov 26, 2009)

Dr. Sarah Lisanby administers TMS
A doctor administers TMS

Research at NewYork-Presbyterian Hospital and other centers has led to the recent FDA approval of transcranial magnetic stimulation (TMS) for the treatment of unipolar depression in patients who have failed to respond to a single antidepressant trial. (1) The approval has opened the door to new treatment options for the more than 50% of patients who fail to respond to an initial course of antidepressant treatment. (2)

Building on previous findings showing the safety and efficacy of TMS in the treatment of major depression, (3) Sarah H. Lisanby, MD, Director of the Brain Stimulation Service Line at NewYork-Presbyterian Hospital/Columbia University Medical Center, and colleagues investigated predictors of response to TMS. The researchers examined data from 301 patients with nonpsychotic unipolar major depression from 23 centers who were randomized to active or sham TMS. Active treatment consisted of TMS at the left dorsolateral prefrontal cortex at 10 pulses per second, 120% of motor threshold, for a total of 3,000 pulses per day for four weeks. Sham treatment was similar to the active treatment except that the TMS coil had a shield to block the magnetic field from entering the brain.

In this study, people who had failed to respond to a single antidepressant medication were significantly more likely to respond to TMS than those who failed two to four antidepressant medication trials (P=0.021).

Sarah H. Lisanby, MD
Sarah H. Lisanby, MD
This finding, on which the FDA indication was based, suggests that patients with more refractory depression may benefit from more potent treatments like electroconvulsive therapy (ECT). Other predictors of response to TMS in this study included absence of a comorbid anxiety disorder, greater depression severity at baseline, female gender, and a shorter illness duration. Dr. Lisanby and colleagues just completed an NIH-sponsored multicenter trial that replicates these findings. The data will be presented at the December 2009 annual meeting of the American College of Neuropsychopharmacology.

While these studies evaluated TMS as a monotherapy, other studies suggest that combination therapy with TMS and antidepressant medications may be more effective than either treatment alone. (4,5) However, "we do need more research to understand what the best augmentation strategy or combination might be," Dr. Lisanby said.

How TMS Works

TMS works by sending a magnetic pulse of less than one millisecond in duration into the left dorsolateral prefrontal cortex, an area of the brain that is typically underactive in depressed patients as shown on functional neuroimaging studies. The pulse triggers an electrical current that stimulates the neurons in that brain area and causes the neurons to fire. Unlike ECT, TMS does not stimulate a large enough number of neurons to induce a seizure when given in accordance with safety guidelines. "What we find is that when TMS treatment is given daily for a period of weeks, people begin to feel a difference in their mood, sleep, appetite, and ability to concentrate, and the symptoms of depression begin to resolve. It takes four to six weeks to see a complete resolution of symptoms, which is about as long as it takes for a medication to work," Dr. Lisanby said. Side effects most commonly include headache and scalp discomfort.

Continued Research at NewYork-Presbyterian Hospital

Dr. Lisanby and colleagues are conducting ongoing research on TMS in the treatment of depression as well as for other indications that are not currently FDA-approved including bipolar disorder, schizophrenia, panic disorder, obsessive-compulsive disorder (OCD), Tourette's Syndrome, depersonalization disorder, autism, and cerebral palsy. "We have a broad spectrum of studies that are using TMS and other forms of brain stimulation techniques to provide help when medications fail and for disorders that don't have effective treatments, like autism," Dr. Lisanby said. "What distinguishes NewYork-Presbyterian from other programs is that we conduct research that contributed to the approval of TMS in the treatment of depression and we are continuing to do studies on ways to augment the efficacy of TMS. The clinical care that we offer is evidence-based and informed by the latest cutting edge research."

For More Information

For more information, please visit brainstimulation.columbia.edu

Faculty Contributing to this Article:

Sarah H. Lisanby, MD, is the Director of the Brain Stimulation Service Line at NewYork-Presbyterian Hospital/Columbia University Medical Center, Director of the Division of Brain Stimulation and Therapeutic Modulation at the New York State Psychiatric Institute (an affiliate of NewYork-Presbyterian Hospital/Columbia University Medical Center), and a Professor of Clinical Psychiatry at Columbia University College of Physicians and Surgeons.

Dr. Lisanby is also the Chair of the National Network of Depression Centers rTMS Task Group, which is developing practice guidelines for TMS care to optimize outcomes in depression. The workgroup is currently tracking how TMS is used in the real world and measuring treatment outcomes.

References

  1. Lisanby SH, Husain MM, Rosenquist PB, et al. Daily left prefrontal repetitive transcranial magnetic stimulation in the acute treatment of major depression: clinical predictors of outcome in a multisite, randomized controlled clinical trial. Neuropsychopharmacology. 2009;34(2):522-534.
  2. Depression Guideline Panel. Depression in primary care. Vol. 2. Treatment of major depression. Clinical practice guideline. No. 5. Rockville, MD: Agency for Health Care Policy and Research, 1999.
  3. O'Reardon JP, Solvason HB, Janicak PG, et al. Efficacy and safety of transcranial magnetic stimulation in the acute treatment of major depression: a multisite randomized controlled trial. Biol Psychiatry. 2007;62(11):1208-1216.
  4. Bretlau LG, Lunde M, Lindberg L, Undén M, Dissing S, Bech P. Repetitive transcranial magnetic stimulation (rTMS) in combination with escitalopram in patients with treatment-resistant major depression: a double-blind, randomised, sham-controlled trial. Pharmacopsychiatry. 2008;41(2):41-47.
  5. Rumi DO, Gattaz WF, Rigonatti SP, et al. Transcranial magnetic stimulation accelerates the antidepressant effect of amitriptyline in severe depression: a double-blind placebo-controlled study. Biol Psychiatry. 2005;57(2):162-166.

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