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Magnetic stimulation helps alleviate auditory hallucinations

Yale University : 28 January, 2003  (New Product)
Psychiatric patients who continue to hear voices despite medication experience relief when an area of the brain responsible for speech perception is stimulated with magnetic waves, Yale researchers have found.
The results of the repetitive transcranial magnetic stimulation study, published this month in the Archives of General Psychiatry, were an improvement over clinical outcomes reported for an earlier study where the magnetic stimulation was applied for a shorter period of time.

Ralph Hoffman, M.D., associate professor of psychiatry at Yale School of Medicine and lead author of the current study, said the patients with schizophrenia received a total of 132 minutes of total stimulation over a nine-day period. In the earlier study, the patients received 40 minutes of stimulation over a four-day period.

'We were trying to see if a more extended protocol could obtain more clinically significant improvements,' he said. 'We did see greater and more sustained improvements in reducing hallucinations as well as an improvement in the patients' overall clinical well being.'

There were 24 patients enrolled in the study. Half were randomly assigned to receive the rTMS and half underwent a sham or placebo form of rTMS. Hoffman is still enrolling patients in the ongoing study. Currently 49 patients have completed the protocol with a similar pattern of results.

Auditory hallucinations are reported by 50 to 70 percent of patients with schizophrenia. A large percentage of patients say the voices they hear are highly distressing, especially when the verbal content is negative or intrusive. Auditory hallucinations disrupt social functioning and are associated with acts of violence and suicide.

In about 25 percent of cases, the auditory hallucinations are not minimized or controlled by medication. The study enrolls patients who are experiencing medication resistant auditory hallucinations at least five times a day.

Hoffman and his colleagues conducted neuroimaging studies of patients during periods when they were experiencing auditory hallucinations and found disturbances appearing in the right and left superior temporal cortex areas, which involve speech perception.

During the rTMS treatment, the patient reclines in a chair and a coil is placed on the scalp over the area of the brain that is believed to be responsible for the auditory hallucinations. Magnetic field pulses, which are delivered once per second, pass undistorted through scalp and skull, inducing electrical currents that briefly activate neurons beneath the coil. Other studies suggest that such stimulation produces prolonged reductions in neural excitability without damaging neurons themselves. During the trial, patients do not know whether they are receiving real or sham stimulation.

Reductions of auditory hallucinations were determined by interviewing patients before and after rTMS by a research psychologist who also did not know the type of stimulation given. Much greater improvements in patients' symptoms were observed following real stimulation compared with sham stimulation.

The treatments, Hoffman said, appeared to well tolerated by the patients. Some reported mild headaches, which were relieved with acetaminophen. Others reported lightheadedness lasting several minutes. Duration of treatment affects ranged from one week up to a full year.

Also involved in the study were Keith Hawkins, Ralitza Gueorguieva, Nash Boutros, M.D., Fady Rachid, M.D., Kathleen Carroll, and John Krystal, M.D., all of the Department of Psychiatry.
22 January 2003

Parkinson's drug may help people quit smoking

A drug used to treat Parkinson's disease, selegiline hydrochloride, also appears to help smokers quit smoking, according to a study at Yale.

The study, published in the January 15 issue of the journal Biological Psychiatry, was conducted by Tony George, M.D., assistant professor of psychiatry at Yale School of Medicine. It is part of work being done through the Center for Nicotine and Tobacco Use Research and the Transdisciplinary Tobacco Use Research Center.

The smokers in the study were all people who had tried to quit smoking numerous times and failed. One of the major themes of CENTURY/TTURC is finding solutions for smokers who find it particularly hard to quit.

'We specifically selected difficult-to-treat smokers because this is the group that hasn't responded to conventional treatments,' said George. 'While there are several effective treatments for smoking cessation, including nicotine replacement therapies and bupropion (Zyban), there are many smokers who do not respond to these drugs. So developing new drugs for smoking cessation is an important undertaking. Selegiline (Deprenyl(tm)) appears to be a drug that might have promise for treatment of nicotine addiction.'

Stephanie O'Malley, M.D., professor of psychiatry at Yale School of Medicine and CENTURY/TTURC's principal investigator, said, 'Dr. George's study is an important contribution to our understanding of the subgroups of people who are not responsive to current treatments.'

George's goal was to evaluate selegiline hydrochloride, a monoamine oxidase B inhibitor, compared to placebo, for the treatment of nicotine dependence in smokers. Inhibition of MAO-B in the brain leads to increases in brain dopamine.

Selegiline is used to treat Parkinson's disease, a neurological disorder associated with dopamine deficiency. A component of cigarette smoke, not nicotine, is known to inhibit brain monoamine oxidase activity in smokers, which was one of the reasons George undertook the study.

The results from George's pilot study are extremely promising. Smoking abstinence rates were significantly higher in the group taking selegiline compared to those taking a placebo. Interestingly, smokers with clinically significant depressive symptoms at the beginning of the study had poorer smoking cessation outcomes compared to those who did not have significant depression.

'This is yet another example of how having co-morbid psychiatric symptoms contributes to poorer smoking cessation outcomes,' George said. He runs the Program for Research in Smokers with Mental Illness, which focuses on understanding how smoking is linked to psychiatric disorders. This is also a major focus of the CENTURY group.

George's study was one of three initial pilot studies for the CENTURY/TTURC group. The Yale TTURC, which is part of CENTURY, receives funding from the National Institute on Drug Abuse, the National Cancer Institute and the Robert Wood Johnson Foundation.
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