Psychiatry 2008 - September 2008 - (Page 15)

Psych Rx PATIENTS TAKING CYMBALTA EXPERIENCED REDUCED CHRONIC LOW BACK PAIN IN NEW STUDY Indianapolis, Indiana— PRNewswire—Data from a new study suggest that Cymbalta (duloxetine HCl) 60–120mg once daily significantly reduced chronic low back pain, as measured by the Brief Pain Inventory (BPI) 24-hour average pain score, compared with placebo. Results from the double-blind, 13-week, placebocontrolled study of 236 patients were presented recently at the annual congress of the European Federation of Neurological Societies (EFNS) in Madrid, Spain. Duloxetine-treated patients reported significantly greater reduction in pain scores than placebotreated patients. Thirty-one percent of duloxetine-treated patients experienced a 50-percent reduction in pain, compared with 19 percent of placebo-treated patients, as measured by an 11-point Likert pain scale. Physicians consider a pain reduction of at least 30 percent as clinically significant. Treatment with duloxetine also was associated with improved patient outcomes as measured by the Patient Global Impressions of Improvement (PGI-I) and physical functioning as measured by the Roland Morris Disability Questionnaire (RMDQ-24). Significantly more patients in the duloxetine group discontinued because of adverse events. In this study, the most common adverse events (those occurring in more than 5% of patients in the duloxetine group) were nausea, dry mouth, fatigue, diarrhea, excessive sweating (hyperhidrosis), dizziness, and constipation. Adverse events were similar to those seen in previous duloxetine studies in other disease states. Additional information is available at www.lilly.com. SCHIZOPHRENIA STUDIES FIND NEW HURDLES Two groups of researchers hunting for schizophrenia genes on a larger scale than ever before have found new genetic variants that point toward a different understanding of the disease. The variants discovered by the two groups, one led by Dr. Kari Stefansson of Decode Genetics in Iceland and the other by Dr. Pamela Sklar of Massachusetts General Hospital, are rare. They substantially increase the risk of schizophrenia but account for a tiny fraction of the total number of cases. This finding, coupled with the general lack of success so far in finding common variants for schizophrenia, raises the possibility that the genetic component of the disease is due to a large number of variants, each of which is very rare, rather than to a handful of common variants. “What is beginning to emerge is that a lot of the risk of brain diseases is conferred by rare deletions,” Dr. Stefansson said. The three variants discovered by his group and Dr. Sklar’s involve the deletion of large sections of DNA from specific sites in a patient’s genome. Their report, published online Wednesday by the journal Nature, follows a finding in March from researchers at the University of Washington in Seattle that rare deletions and duplications of DNA figure prominently in schizophrenia. The new focus on rare mutations suggests that natural selection is highly efficient at removing schizophrenia-causing genes from the population. Despite selection against the disease, according to this new idea, schizophrenia continues to appear because it is driven by a spate of new mutations that occur all the time in the population. “We’ve looked for common variants in schizophrenia and get almost nothing,” said Dr. David Goldstein, a geneticist at Duke University and one of Dr. Stefansson’s co-authors. “This means natural selection has done a really good job of purging them away, and we’re left with rare variants, a constant flow of them, as the principal driver of the disease.” “This may be the case in other brain diseases, too,” Dr. Goldstein said, “because successful cognitive functioning is a highly complex system and there are many independent ways to take it down.” One obvious way in which natural selection acts against the disease is that people with schizophrenia have fewer children than others. “The brain diseases are those where we find the biggest evidence for negative selection,” Dr. Stefansson said, a finding he found surprising because “I would have thought the brain was a luxury organ when it comes to reproductive success.” Devising treatments for schizophrenia could be more difficult if the disease is caused by subsets of 2,000 rare variants, say, rather than by just 20 common ones. But several experts said it was too early to know what mix of common and rare variants may cause the disease and whether that might affect the search for treatments. The search for common variants in schizophrenia, however, has not been very successful so far, though not for want of trying. There have been more than a thousand studies, implicating 3,608 genetic variants. But when all the data are pooled, only 24 of those variants turn out to be statistically significant, according to an analysis in the current issue of Nature Genetics by a group led by Dr. [SEPTEMBER] Psychiatry 2008 15 http://www.lilly.com

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Psychiatry 2008 - September 2008 Editor’s Message Editorial Advisory Board Contents Psych Rx Letters to the Editor Use of Benzodiazepines in the Treatment of Anxiety Functional Neurosurgery in the Treatment of Severe Obsessive Compulsive Disorder and Major Depression: Overview of Disease Circuits and Therapeutic Targeting for the Clinician Treatment of Comorbid Adolescent Cannabis Use and Major Depressive Disorder Risperidone Long-acting Injections: Successful Alternative Deltoid Muscle Injections for Refractory Schizophrenia Alcohol/Substance Misuse and Treatment Nonadherence: Fatal Attraction Transforming the Psychiatric Inpatient Unit from Short-term Pseudo-asylum Care to State-of-the-art Treatment Setting Journal Watch Classified Advertising Information for Authors

Psychiatry 2008 - September 2008

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