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 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.