Eli Lilly and Company announced that the US Food and Drug Administration (FDA) has approved Symbyax (olanzapine and fluoxetine HCl) for the treatment of depressive episodes associated with bipolar disorder. Symbyax (pronounced simm-bee-ax), which is a combination of olanzapine, the active ingredient in Zyprexa, and fluoxetine, the active ingredient in Prozac, is the first FDA-approved medication for bipolar depression, a notoriously difficult-to-treat condition that afflicts millions of Americans.
"There is a desperate need for an effective treatment for bipolar depression, a devastating condition which often leads patients to take their own lives," said Terence A Ketter, MD, associate professor of psychiatry & behavioural sciences, and chief, Bipolar Disorders Clinic, Stanford University School of Medicine.
"We are pleased to be able to provide clinicians with Symbyax, the first FDA-approved option to help physicians help their patients with bipolar depression," said Mauricio Tohen, MD, PhD, Lilly clinical research fellow, Lilly Research Laboratories and Zyprexa product team leader. "Patients suffering from this debilitating condition can now benefit from the combination of the active ingredients in Zyprexa and Prozac, two of the most successful and proven medications in neuroscience history."
Bipolar disorder is a complex mental illness characterized by debilitating mood swings ranging from episodes of deep depression marked by feelings of extreme guilt, sadness, anxiety and, at times, suicidal thoughts to episodes of mania (abnormal euphoria, elation and irritability), interspersed with periods of normal mood.
Patients with bipolar disorder spend more than three times longer in the depressive phase than in the manic phase of the disorder and take longer to recover from it. Additionally, the depressive phase of bipolar disorder is associated with higher rates of morbidity and mortality. It is estimated that one in four people with bipolar disorder will attempt suicide at least once, and the relative risk of suicide among patients with bipolar depression has been shown to be nearly 35 times greater than for patients in the manic phase of bipolar disorder.
According to a study (Tohen, et al.) published in the November 2003 issue of Archives of General Psychiatry, Symbyax helped to treat the symptoms of bipolar depression more effectively and at a significantly faster rate than placebo. In the pooled eight-week studies, patients in the Symbyax group experienced significantly greater improvement in depressive symptoms at weeks one, three, four, six and eight, compared with patients taking placebo. That robust symptom improvement was sustained throughout the entire eight weeks of the study. In addition, Symbyax patients had no statistically greater risk of treatment-emergent mania than patients taking placebo. In patients with bipolar depression, a manic episode is a potential consequence of treatment with a conventional antidepressant alone.
"Medications that clinicians have traditionally used to treat bipolar patients in a depressive phase can often take several weeks to work and have the additional risk of sending the patient into a manic episode," said Ketter. "Having a medication that can provide symptom relief quickly, while avoiding mania, will be so important to physicians in effectively treating patients with bipolar depression, particularly because these individuals are at a high risk of suicide."
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.
Bipolar disorder, also known as manic-depressive illness, affects an individual's mood, behavior and thinking. Unlike many illnesses, symptoms may be quite different in different phases of the illness. Treatment is more challenging because some therapies that are effective in one phase of the illness may be counterproductive in another, such as the observation that treatment with an antidepressant alone can precipitate manic episodes.
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. An estimated 25 per cent of patients with bipolar disorder attempt suicide at least once and approximately 20 per cent actually succeed. This is one of the highest rates for any psychiatric disorder and three times higher than that of the general population. The World Health Organization estimates that bipolar disorder is the sixth leading cause of disability in the world.