Capsules may be effective in treating bipolar disorder

University of North Carolina at Chapel Hill researchers have announced study results finding that a formulation of
three-beaded extended-release carbamazepine capsules (ERC-CBZ) was effective, safe and tolerable in the treatment of bipolar
I disorder and showed no clinically significant weight gain or changes in blood glucose between treatment groups.


The pooled data presented by UNC researchers today (Nov. 18) at the 17th annual U.S. Psychiatric and Mental Health Congress
in San Diego are results from two of the first trials to use an extended-release form of carbamazepine capsules manufactured
by Shire Pharmaceuticals.


"People affected by bipolar disorder experience intense highs and-or irritability, which may be followed or paired with
crippling lows. Bipolar patients also may be affected by additional disorders including anxiety disorders, attention deficit
disorder and substance abuse," said Dr. Richard H. Weisler, primary investigator of both clinical trials and adjunct
professor of psychiatry at UNC's School of Medicine.


"Many patients at present still either fail to respond or have trouble tolerating medications for their bipolar disorder. For
this reason, finding a treatment regimen that works effectively in both manic states and the large number of mixed patients
who are both seriously depressed and manic at the same time is a very important addition to our treatment options for
patients and their doctors."


Weisler also is adjunct assistant professor of psychiatry and behavioral sciences at Duke University Medical Center and has a
private practice in Raleigh.


More than 2 million American adults are estimated to have bipolar disorder in any given year. In fact, recent research
suggests approximately one in 30 adults suffer from bipolar disorder. Bipolar disorder, also known as manic-depressive
illness, is characterized by episodes of mania and depression while experiencing periods of normal mood in between. Although
bipolar disorder can have devastating effects on an individual's life, it is often not recognized as an illness and the
majority of people may suffer for years before it is properly diagnosed and treated.


"Proper diagnosis and earlier treatment can usually alter the course of the illness," said Weisler.


This analysis of pooled data resulted from two identically designed, three-week, double-blind, placebo-controlled phase 3
trials of ERC-CBZ monotherapy in patients initially requiring hospitalization. The trial involved 443 patients ages 18 to 76
years with a Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV) diagnosis of bipolar disorder
(current episode manic or mixed) who were randomized to double-blind treatment with either ERC-CBZ or placebo.















Efficacy was assessed by Young Mania Rating Scale (YMRS), Clinical Global Impression-Severity (CGI-S), Clinical Global
Impression-Improvement (CGI-I), and Hamilton Depression Rating Scale (HDRS). Safety and tolerability were assessed by
measurements of weight, blood glucose, cholesterol and interval between heartbeats, as well as adverse event monitoring.



ERC-CBZ treatment was initiated at 200 milligrams twice daily and titrated, as necessary, by 200 milligrams per day up to
1,600 milligrams per day. The average final dose of ERC-CBZ was 700 milligrams per day, with many patients receiving 400 to
600 milligrams at final daily dose.


Of the 443 patients, 240 (54.2 percent) completed the study. Treatment with ERC-CBZ was associated with significant
improvements in mean YMRS total scores at all time points during the trial. At the end of the trial, significant reductions
in YMRS total scores were observed in both manic and mixed patients. Furthermore, significant improvements were shown in
CGI-I and CGI-S scores. Total score improvements in HDRS were observed in ERC-CBZ treated mixed patients at endpoint.



ERC-CBZ was generally well-tolerated in both manic and mixed bipolar patients. The 240 patients in the final group
demonstrated no clinically significant weight gain, no significant changes in blood glucose and intervals between heartbeats
between treatment groups, and no serious rashes, blood disorders or ECG adverse events. Treatment with ERC-CBZ caused a
modest increase in total cholesterol of 21.1 milligrams/deciliter of which about 20 percent was the beneficial HDL
cholesterol. Common treatment-emergent adverse events were mild to moderate in nature and included dizziness, somnolence,
nausea, vomiting and loss of coordination. However, these events were transient and most occurred during the first week of
treatment.


Of patients recruited into the trial, 79 percent were from the United States and 21 percent from India; and 58.5 percent were
white, 14.8 percent black and 26.7 percent were other ethnicities. The mean age of patients was 37.5 years of age, and 62
percent were male. Mixed presentation patients accounted for 34 percent and 62 percent of patients suffered from mania.



Weisler's co-authors in this study were Dr. R. Hirschfeld of the University of Texas Medical Branch at Galveston, Dr. A. J.
Cutler of the University of South Florida, Dr. T. Gazda of St. Luke's Medical Center, Dr. T. Ketter of Stanford University
School of Medicine, Dr. P. Keck of the University of Cincinnati College of Medicine; Dr. A. Swann of the University of Texas
Medical School at Houston and Dr. A. Kalali of Quintiles CNS Therapeutics in San Diego.


Funding for the study was provided by Shire.


Note: Weisler will present the findings of the new study from 3:45 p.m. to 6:45 p.m. Pacific time.


UNC School of Medicine contact: Stephanie Crayton, 919-966-2860 or scraytonunch.unc. UNC News Services contact: Deb
Saine, 919-962-8415 or deborah_saineunc.


Contact: Stephanie Crayton, UNC School of Medicine

919-966-2860

Porter Novelli