Latest Treatments
Schering-Plough Announces FDA Approval Of SAPHRIS(R) (asenapine) For Acute Treatment Of Schizophrenia In Adults And Manic Or Mixed Episodes Of Bipolar
Schering-Plough Corporation (NYSE: SGP) announced that the U.S. Food and Drug Administration (FDA) has approved SAPHRIS((R)) (asenapine) sublingual tablets for acute treatment of schizophrenia in adults and acute treatment of manic or mixed episodes associated with bipolar I disorder with or without psychotic features in adults. SAPHRIS can be used as a first-line treatment and is the first psychotropic drug to receive initial approval for both of these indications simultaneously.
"We are very pleased with the U.S. approval of SAPHRIS, which represents an important new choice for acute treatment of schizophrenia and acute manic or mixed episodes of bipolar I disorder in patients starting treatment and those who have discontinued previous treatment," said Thomas P. Koestler, Ph.D., executive vice president and president, Schering-Plough Research Institute. "SAPHRIS is an important addition to Schering-Plough's product portfolio, and represents the first U.S. approval resulting from the Organon/Schering-Plough combination."
SAPHRIS is expected to be available in the U.S. during the fourth quarter of 2009.
Schizophrenia affects about 24 million people worldwide, including two million Americans, and bipolar I disorder affects about 1 percent of adults, including 10 million Americans.
"Schizophrenia and bipolar I disorder are complex medical conditions that can present clinical challenges for the physician," said Steven G. Potkin, M.D., professor, department of psychiatry and human behavior, University of California, Irvine, and lead author of a pivotal schizophrenia study as part of the SAPHRIS clinical development program.
"Having a new FDA-approved treatment such as SAPHRIS is important in these serious conditions because physicians need options to help manage their patients' symptoms," said Roger S. McIntyre, M.D., associate professor of psychiatry and pharmacology, University of Toronto, Canada, and lead author of the pivotal bipolar mania studies as part of the SAPHRIS clinical development program.
The FDA approval of SAPHRIS is based on a New Drug Application (NDA) that included efficacy data from a clinical study program involving more than 3,000 patients in schizophrenia and bipolar mania trials. The SAPHRIS filing was supported by safety data in 4,500 people, with some patients treated for more than two years. The approval is based on acute schizophrenia trials in which SAPHRIS (5 mg twice daily) demonstrated statistically significant efficacy versus placebo and acute bipolar I disorder studies in which SAPHRIS (10 mg twice daily) demonstrated statistically significant reduction of bipolar mania symptoms versus placebo.
About SAPHRIS (asenapine)
SAPHRIS is a psychotropic agent indicated for acute treatment of schizophrenia in adults and acute treatment of manic or mixed episodes associated with bipolar I disorder with or without psychotic features in adults. Schering-Plough has reported additional top-line results for SAPHRIS in long-term clinical studies. Additional clinical studies with SAPHRIS are ongoing.
In Europe, a Marketing Authorization Application (MAA) for asenapine, under the brand name SYCREST((R)), is currently under review by the European Medicines Agency (EMEA) for the treatment of schizophrenia and manic episodes associated with bipolar I disorder. The application will follow the Centralized Procedure.
Schering-Plough acquired asenapine in November 2007 through its acquisition of Organon BioSciences, which developed the product.
Important Safety Information about SAPHRIS
Increased Mortality in Elderly Patients with Dementia-Related Psychosis:
Elderly patients with dementia-related psychosis treated with antipsychotic drugs are at an increased risk of death. Analyses of 17 placebo-controlled trials (modal duration of 10 weeks), largely in patients taking atypical antipsychotic drugs, revealed a risk of death in the drug-treated patients of between 1.6 to 1.7 times that seen in placebo-treated patients. Over the course of a typical 10-week controlled trial, the rate of death in drug-treated patients was about 4.5 percent compared to a rate of 2.6 percent in the placebo group. Although the causes of death were varied, most of the deaths appeared to be either cardiovascular (e.g., heartfailure, sudden death) or infectious (e.g.,pneumonia) in nature. SAPHRIS is not approved for the treatment of patients with dementia-related psychosis.
Cerebrovascular Adverse Events: There was a higher incidence of cerebrovascular adverse reactions (cerebrovascular accidents and transient ischemic attacks) including fatalities compared to placebo-treated subjects. SAPHRIS is not approved for the treatment of patients with dementia-related psychosis.
Neuroleptic Malignant Syndrome (NMS): NMS, a potentially fatal symptom complex, has been reported with administration of antipsychotic drugs, including SAPHRIS. NMS can cause hyperpyrexia, muscle rigidity, altered mental status, irregular pulse or blood pressure, tachycardia, diaphoresis and cardiac dysrhythmia. Additional signs may include elevated creatine phosphokinase, myoglobinuria (rhabdomyolysis) and acute renal failure. Management should include immediate discontinuation of antipsychotic drugs and other drugs not essential to concurrent therapy, intensive symptomatic treatment and medical monitoring, and treatment of any concomitant serious medical problems.
Tardive Dyskinesia (TD): The risk of developing TD and the potential for it to become irreversible may increase as the duration of treatment and the total cumulative dose increase. However, the syndrome can develop, although much less commonly, after relatively brief treatment periods at low doses. Prescribing should be consistent with the need to minimize TD. If signs and symptoms appear, discontinuation should be considered.
Hyperglycemia and Diabetes Mellitus: Hyperglycemia, in some cases associated with ketoacidosis, hyperosmolar coma or death, has been reported in patients treated with atypical antipsychotics. Patients with risk factors for diabetesmellitus who are starting treatment with atypical antipsychotics should undergo fasting blood glucose testing at the beginning of and during treatment. Any patient treated with atypical antipsychotics should be monitored for symptoms of hyperglycemia including polydipsia, polyuria, polyphagia and weakness. Patients who develop symptoms of hyperglycemia during treatment with atypical antipsychotics should also undergo fasting blood glucose testing. In some cases, hyperglycemia has resolved when the atypical antipsychotic was discontinued; however, some patients required continuation of anti-diabetic treatment despite discontinuation of the antipsychotic drug.
Weight Gain: In short-term schizophrenia and bipolar mania trials, there were differences in mean weight gain between SAPHRIS-treated and placebo-treated patients. In a 52 week study, the proportion of patients with an equal to or greater than 7 percent increase in body weight was 14.7 percent.
Orthostatic Hypotension and Syncope and Other Hemodynamic Effects: SAPHRIS may induce orthostatic hypotensionand syncope. SAPHRIS should be used with caution in patients with known cardiovascular disease, cerebrovascular disease, conditions which would predispose them to hypotension and in the elderly. SAPHRIS should be used cautiously when treating patients who receive treatment with other drugs that can induce hypotension, bradycardia, respiratory or central nervous system depressionMonitoring of orthostatic vital signs should be considered in all such patients, and a dose reduction should be considered if hypotension occurs.
Leukopenia, Neutropenia, and Agranulocytosis: In clinical trial and postmarketing experience, events of leukopenia/neutropenia have been reported temporally related to antipsychotic agents, including SAPHRIS. Patients with a pre-existing low white blood cell count (WBC) or a history of leukopenia/neutropenia should have their complete blood count (CBC) monitored frequently during the first few months of therapy and SAPHRIS should be discontinued at the first sign of a decline in WBC in the absence of other causative factors.
QT Prolongation: SAPHRIS was associated with increases in QTc interval ranging from 2 to 5 msec compared to placebo. No patients treated with SAPHRIS experienced QTc increases of equal to or greater than 60 msec from baseline measurements, nor did any experience a QTc of equal to or greater than 500 msec. SAPHRIS should be avoided in combination with other drugs known to prolong QTc interval, in patients with congenital prolongation of QT interval or a history of cardiacarrhythmias, and in circumstances that may increase the occurrence of torsades de pointes and/or sudden death in association with the use of drugs that prolong the QTc interval.
Hyperprolactinemia: Like other drugs that antagonize dopamine D2 receptors, SAPHRIS can elevate prolactin levels, and the elevation can persist during chronic administration. Galactorrhea, amenorrhea, gynecomastia and impotence have been reported in patients receiving prolactin-elevating compounds.
Seizures: SAPHRIS should be used cautiously in patients with a history of seizures or with conditions that lower seizure threshold, e.g., Alzheimer's dementia
Dysphagia: Esophageal dysmotility and aspiration have been associated with antipsychotic drug use. Aspiration pneumonia is a common cause of morbidity and mortality in elderly patients, in particular those with advanced Alzheimer's dementia. SAPHRIS is not indicated for the treatment of dementia-related psychosis, and should not be used in patients at risk for aspiration pneumonia.
Potential for Cognitive and Motor Impairment: Somnolence was reported in patients treated with SAPHRIS. Patients should be cautioned about performing activities requiring mental alertness, such as operating hazardous machinery or operating a motor vehicle, until they are reasonably certain that SAPHRIS therapy does not affect them adversely.
Suicide: The possibility of suicide attempt is inherent in psychotic illnesses andbipolar disorder. Close supervision of high-risk patients should accompany drug therapy. Prescriptions for SAPHRIS should be written for the smallest quantity of tablets in order to reduce the risk of overdose.
SAPHRIS is not recommended in patients with severe hepatic impairment.
Co-administration of SAPHRIS with strong CYP1A2 inhibitors (fluvoxamine) or compounds which are both CYP2D6 substrates and inhibitors (paroxetine) should be done with caution.
Commonly observed adverse reactions (incidence equal to or greater than 5 percent and at least twice that for placebo) were: Patients with Schizophrenia: akathisia, oral hypoesthesia and somnolence. Patients with Bipolar Disorder: somnolence, dizziness, extrapyramidal symptoms other than akathisia and weight increase.
University of Pittsburgh School of Medicine study published in Bipolar Disorders
PITTSBURGH, January 3, 2008 — Bright light therapy can ease bipolar depression in some patients, according to a study published in the journal Bipolar Disorders. Researchers from the University of Pittsburgh School of Medicine’s Western Psychiatric Institute and Clinic studied nine women with bipolar disorder to examine the effects of light therapy in the morning or at midday on mood symptoms.
“There are limited effective treatments for the depressive phase of bipolar disorder,” said Dorothy Sit, M.D., assistant professor of psychiatry and the study’s first author. “While there are treatments that are effective for mania, the major problem is the depression, which can linger so long that it never really goes away.”
In this study, women with bipolar depression were given light boxes and instructed on how to use them at home. The women used the light boxes daily for two-week stretches of 15, 30 and 45 minutes. Some patients responded extremely well to the light therapy, and their symptoms of depression disappeared. The responders to light therapy stayed on the light therapy for an additional three or four months. Four patients received morning light, and five used their light boxes at midday. Participants also continued to take their prescribed medications throughout the study period.
“Three of the women who received morning light initially developed what we call a mixed state, with symptoms of depression and mania that occur all at once – racing thoughts, irritability, sleeplessness, anxiety and low mood,” said Dr. Sit. “But when another group began with midday light therapy, we found a much more stable response.”
Of the nine women treated, six achieved some degree of response, with several reaching full recovery from depressive symptoms. While most attained their best recovery with midday light, a few responded more fully to a final adjustment to morning light.
“People with bipolar disorder are exquisitely sensitive to morning light, so this profound effect of morning treatment leading to mixed states is very informative and forces us to ask more questions,” said Dr. Sit. “Did we introduce light too early and disrupt circadian rhythms and sleep patterns?”
People with bipolar disorder are known to be sensitive to changes in outdoor ambient light and to seasonal changes. Researchers are asking whether the risk of suicide in patients with bipolar disorder could be linked to changes in light exposure.
“In our study, 44 percent of patients were full responders, and 22 percent were partial responders,” Dr. Sit and her colleagues write. “Light therapy, therefore, is an attractive and possibly effective augmentation strategy to improve the likelihood of full-treatment response.”
Optimal response was observed with midday light therapy for 45 or 60 minutes daily, noted Dr. Sit.
Other study authors are Katherine L. Wisner, M.D., Barbara H. Hanusa, Ph.D., and Stacy D. Stull, M.S., all of the Women’s Behavioral HealthCARE program at Western Psychiatric Institute and Clinic; and Michael Terman, Ph.D., Columbia University.
Researchers report funding from the Stanley Foundation, the University of Pittsburgh School of Medicine, National Institute of Mental Health, U.S. Department of Health and Human Services, Pfizer Inc., GlaxoSmithKline and the National Institute of Neurological Disorders and Stroke.
Cover Story on Bipolar Disorder in Children
Read the New York Times Magazine article
Diagnoses of bipolar disorder among children are on the rise, but little is known about the disease in children. As a national leader in pediatric bipolar disorder research and clinical treatment, WPIC has the only clinic in the U.S. solely dedicated to treating children with this illness.
Highly recognized child psychiatry experts, David A. Axelson, M.D. and Boris Birmaher, M.D., have developed the largest and most comprehensive treatment clinic for pediatric bipolar disorder ?in the country.
About WPIC
Western Psychiatric Institute and Clinic (WPIC) is considered to be one of the nation’s foremost university-based psychiatric care facilities and one of the world’s leading centers for research and treatment of mental health disorders. WPIC houses the Department of Psychiatry of the University of Pittsburgh School of Medicine and is the flagship of UPMC Behavioral Health, the psychiatric specialty division of the University of Pittsburgh Medical Center.
Named among the best psychiatric hospitals in the country by U.S. News & World Report, WPIC has more than 60 outpatient programs and 289 licensed inpatient beds, serving individuals across the lifespan, from young children to aging adults. Each year, more than 40,000 individuals receive care through inpatient and outpatient clinical programs at WPIC.
Its research programs are unsurpassed, with researchers from the University of Pittsburgh School of Medicine’s department of psychiatry receiving more federal funding for behavioral health and addiction research than any other institution in the nation. In 2007, the department received more than $72 million in funding from the National Institutes of Health, ranking it first in funding among all psychiatry departments, a distinction the department has earned for more than a decade. Approximately 80 percent of this funding supports clinical research projects, many of which directly benefit individuals who receive services at WPIC or through UPMC Behavioral Health.
WPIC currently houses six federally funded Centers of Excellence: the Mental Health Intervention Center for Mood and Anxiety Disorders, the Conte Center for the Neuroscience of Mental Disorders, the Advanced Center for Intervention and Services Research for Late-Life Mood Disorders, the Pittsburgh Mind/Body Center, the Affect Regulation and Adolescent Brain Center and the Advanced Center for Intervention and Services Research for Early Onset Mood and Anxiety Disorders. Other specialty areas include: Alzheimer’s disease, sleep and sleep disorders, schizophrenia, autism, suicide and eating disorders.
WPIC offers a number of educational and training programs. For professionals, these programs include internship, residency, fellowship and post-doctoral research programs. For the public, outreach programs include crisis, disaster and bioterrorism preparedness training, intimate partner violence training, and school-based training to aid teachers and counselors in recognizing and helping students at risk for mental illness ?and suicide.
For information on the latest Bipolar Research and treatment please visit:
Pitt Researchers to Study Effects of Early Intervention for Children of Parents with Bipolar Disorder
… for developing bipolar disorder is having one or more family members with the illness, identifying … that people with bipolar disorder, and those vulnerable to developing bipolar disorder, have especi … Individuals with bipolar disorder who are the parents of a child between the ages of 12 and 18 who d … - 33KB
Bipolar Disorder
Bipolar I and Bipolar II are subtypes of the illness. … Bipolar disorder typically emerges in adolescence or early adulthood. … of people with bipolar disorder have at least one close relative with either bipolar disorder or ma … - 33KB
