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FDA Approves Zyprexa (Olanzapine) for Maintenance of Bipolar Disorder

INDIANAPOLIS, IN -- January 15, 2004 -- The U.S. Food and Drug Administration (FDA) has approved Zyprexa® (olanzapine) for maintenance in the treatment of bipolar disorder, Eli Lilly and Company announced today. This FDA approval recognizes that Zyprexa is an effective treatment to delay relapse into either mania or depression in patients with bipolar disorder. Zyprexa is the first treatment in nearly 30 years to be recognized by the FDA as a treatment for both acute mania and maintenance treatment in bipolar disorder.

"Bipolar disorder is a serious condition that can be difficult to treat. For those who achieve stability on existing medications, relapse of symptoms is all too common," said Frederick K. Goodwin, MD, Director, Center on Neuroscience, Medical Progress and Society, at the George Washington University Medical Center, Washington, D.C. "It is good news that the FDA has now approved Zyprexa as a new tool for physicians to use to delay relapse and prolong periods of stability and wellness."

Zyprexa was approved by the FDA in 2000 for the short-term treatment of acute mixed or manic episodes associated with bipolar disorder and is the first medication approved to both treat acute mania and delay relapse of symptoms associated with bipolar disorder since lithium received approval from the FDA in 1974. In addition, the FDA recently approved Symbyax™ for the treatment of bipolar depression. Symbyax combines the active ingredients in Zyprexa and Prozac®, and is the first and only FDA-approved treatment for this devastating and difficult-to-treat phase of bipolar disorder.

Zyprexa Delayed Relapse Into Both Mania and Depression in Clinical Trials

The new indication is based on data from a double-blind, placebo- controlled study that showed time to relapse of either mania or depression was significantly longer for Zyprexa patients than patients treated with placebo. Zyprexa-treated patients had a significantly lower rate of either a mania (16.4 percent for Zyprexa versus 41.2 percent for placebo) or depression relapse (34.7 percent for Zyprexa versus 47.8 percent for placebo).

"We believe that physicians are looking for treatments, like Zyprexa, that demonstrate that they can effectively delay relapse, not only into the manic phase, but also into the depressive phase of bipolar disorder," said Mauricio Tohen, MD, Dr. P.H., Lilly clinical research fellow, Lilly Research Laboratories and Zyprexa product team leader. "This new indication provides a treatment option to clinicians and patients that is dependable in treating both acute manic episodes and delaying new episodes. Longer stable periods may provide greater opportunities for clinicians to work with their patients on improving work or family life."

In the placebo-controlled study, common and significant adverse events for the Zyprexa patients were weight gain, fatigue and inner and outer restlessness (akathisia).

About Bipolar Disorder

Bipolar disorder, also known as manic-depressive illness, is a complex mental illness characterized by debilitating swings in mood. These swings range from manic episodes, marked by abnormal euphoria, elation and irritability, to episodes of deep depression, marked by extreme sadness and difficulty functioning. These periods of illness are interspersed with periods of normal mood. Although a lifelong illness, bipolar disorder typically emerges in adolescence or young adulthood, and episodes continue intermittently throughout life.

More than 2.5 million Americans live with a diagnosis of bipolar disorder but recent research indicates the real number may be as high as 10 million. The results of untreated bipolar disorder can be catastrophic. According to the National Institute of Mental Health, nearly one in every five people with the illness ends their life by suicide. The World Health Organization estimates that bipolar disorder is the sixth leading cause of disability in the world.

During relapse into mania or depression, people with bipolar disorder may experience disruptions in relationships and jobs, suffer feelings of failure or become suicidal. Recurring relapse may lead to both a worsening of the disease itself and may contribute to more frequent episodes of relapse.

Important Information About Zyprexa and Symbyax

In addition to the newly approved indication, Zyprexa is indicated in the United States for the short-term and long-term treatment of schizophrenia, and either alone or in combination with lithium or valproate (Depakote(R), Abbott) for the short-term treatment of acute mixed or manic episodes associated with bipolar disorder. Since Zyprexa was introduced in 1996, it has been prescribed to more than 12.5 million people worldwide.

The most common treatment-emergent adverse event associated with Zyprexa in placebo-controlled, short-term schizophrenia and bipolar mania trials was drowsiness. Other common events were dizziness, weight gain, personality disorder (COSTART term for nonaggressive objectionable behavior), constipation, restlessness, episodes of low blood pressure, dry mouth, weakness, upset stomach, increased appetite, and tremor. A small number of patients experienced asymptomatic elevations of certain liver enzymes; none of these patients experienced jaundice.

Hyperglycemia, in some cases associated with ketoacidosis, coma, or death, has been reported in patients treated with atypical antipsychotics including Zyprexa. Assessment of the relationship between atypical antipsychotic use and glucose abnormalities is complicated by the possibility of an increased background risk of diabetes mellitus in patients with schizophrenia and the increasing incidence of diabetes mellitus in the general population. The available data are insufficient to provide reliable estimates of differences in hyperglycemia-related adverse event risk among the marketed atypical antipsychotics. All patients taking atypicals should be monitored for symptoms of hyperglycemia. Persons with diabetes who are started on atypicals should be monitored regularly for worsening of glucose control; those with risk factors for diabetes should undergo baseline and periodic fasting blood glucose testing. Patients who develop symptoms of hyperglycemia during treatment should undergo fasting blood glucose testing.

Prescribing should be consistent with the need to minimize the risk of neuroleptic malignant syndrome, tardive dyskinesia, seizures and low blood pressure. In short-term (six-week) acute bipolar mania trials in combination with lithium or valproate, the most common treatment emergent adverse event associated with Zyprexa and lithium or valproate was dry mouth. Other common events were weight gain, increased appetite, dizziness, back pain, constipation, speech disorder, increased salivation, amnesia and abnormal burning or tingling of the skin.

Although the efficacy of Zyprexa in elderly patients with dementia has not been established in clinical trials and Zyprexa is not approved for use in this patient population, it is important to note the label for Zyprexa includes a warning for elderly patients with dementia. The warning states that strokes or mini-strokes (also called transient ischemic attacks or TIAs), including fatalities were reported in elderly patients with dementia-related psychosis participating in Zyprexa clinical trials.

Full prescribing information is available at http://www.zyprexa.com. Symbyax is indicated in the United States for the treatment of depressive episodes associated with bipolar disorder. The most common adverse events reported in patients taking Symbyax in clinical trials was drowsiness. Other common events noticed in clinical trials were weight gain, increased appetite, feeling weak, swelling, tremor, sore throat, and difficulty concentrating.

Hyperglycemia, in some cases associated with ketoacidosis, coma or death, has been reported in patients treated with atypical antipsychotics, including olanzapine, and concomitant olanzapine and fluoxetine. Assessment of the relationship between atypical antipsychotic use and glucose abnormalities is complicated by the possibility of an increased background risk of diabetes mellitus in patients with schizophrenia and the increasing incidence of diabetes mellitus in the general population. The available data are insufficient to provide reliable estimates of differences in hyperglycemia- related adverse-event risk among the marketed atypical antipsychotics. All patients taking atypicals should be monitored for symptoms of hyperglycemia.

Persons with diabetes who are started on atypicals should be monitored regularly for worsening of glucose control; those with risk factors for diabetes should undergo baseline and periodic fasting blood-glucose testing. Patients who develop symptoms of hyperglycemia during treatment should undergo fasting blood-glucose testing.

Although Symbyax is not approved for elderly patients with dementia it is important to note the label for Symbyax includes a warning for patients in this population. The warning states that strokes or mini-strokes (also called transient ischemic attacks or TIAs), including fatalities were reported in elderly patients with dementia-related psychosis participating in clinical trials for olanzapine, an active ingredient in Symbyax. In fact, Symbyax has not been studied in elderly patients with dementia, nor do we expect Symbyax to be used to treat these patients.

Symbyax may induce orthostatic hypotension (a drop in blood pressure when standing up), associated with dizziness, speeding or slowing of heart rate, and in some patients, fainting, especially during initial therapy.

Symbyax prescribing should be consistent with the need to minimize the risk of neuroleptic malignant syndrome, tardive dyskinesia, and orthostatic hypotension.

Symbyax should not be administered until at least two weeks have passed since discontinuing an MAO inhibitor, and an MAO inhibitor is contraindicated for at least five weeks after discontinuation with Symbyax. Thioridazine should not be administered with Symbyax or within a minimum of 5 weeks after discontinuing Symbyax. Symbyax should be discontinued immediately if rash or other possibly allergic phenomena appear for which an alternative explanation cannot be identified.

Due to the cyclical nature of bipolar disorder, patients should be monitored for the signs of mania and hypomania during treatment with Symbyax.

Patients should inform their physicians if they are taking Zyprexa, Prozac, Sarafem or fluoxetine.

Full prescribing information is available at http://www.symbyax.com.


SOURCE: Eli Lilly and Company

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