Symbyax(TM) Shown to Reduce Symptoms Associated With Suicidal Thinking in Patients With Bipolar Depression
May 05 2004 - 4:00PM
PR Newswire (US)
Symbyax(TM) Shown to Reduce Symptoms Associated With Suicidal
Thinking in Patients With Bipolar Depression Those With Early-Onset
of Bipolar Disorder Also Shown More Likely to Respond to Symbyax
Treatment NEW YORK, May 5 /PRNewswire-FirstCall/ -- New data show
that Symbyax(TM) (olanzapine and fluoxetine HCl) reduced the
symptoms associated with suicidal ideation (having thoughts of
suicide), a predictor of suicidal behavior, in bipolar depressed
patients within the first week of treatment. Another study
demonstrated that having an early onset of bipolar disorder tripled
the likelihood that a patient might respond to Symbyax. These
findings were presented today at the annual meeting of the American
Psychiatric Association. Symbyax is the first and only FDA-approved
treatment for the depressive phase of bipolar disorder. "These data
provide hope to patients whose lives are disrupted by bipolar
depression, a devastating and difficult condition to treat that
often results in suicide or suicide attempts," said Terence A.
Ketter, M.D., associate professor of psychiatry & behavioral
sciences, and chief, Bipolar Disorders Clinic, Stanford University
School of Medicine. "The rapid reduction of symptoms associated
with suicidal ideation suggests the potential benefit of Symbyax
among bipolar depressed patients, who are at high risk of taking
their own lives." Key Findings Suicidal Ideation Study An
eight-week analysis of 688 people that compared Symbyax (n=73),
olanzapine (n=299) and placebo (n=316) in the treatment of bipolar
I depression showed: * Suicidal ideation, as measured by the
Montgomery-Asberg Depression Rating Scale item 10 (MADRS-10), was
significantly reduced in bipolar depressed patients by the first
week of Symbyax treatment compared to patients receiving placebo or
olanzapine. * Symbyax significantly improved the symptoms of
apparent sadness, reported sadness, pessimistic thoughts, and inner
tension -- four MADRS items correlated to suicidal ideation --
within one week compared to placebo. Predictors of Response Study
In addition, a statistical analysis performed on acute phase data
from a double-blind, randomized clinical trial comparing Symbyax
(n=86), olanzapine (n=370) and placebo (n=377) in patients with
bipolar depression found: * Having an early onset of bipolar
disorder (prior to age 20) tripled the odds of response to Symbyax
among patients with bipolar depression. Response was defined as a
greater than 50 percent decrease in Montgomery-Asberg Depression
Rating Scale (MADRS) total score. * Early onset was the only
independent variable evaluated that was significant for predicting
response to Symbyax among patients with bipolar depression. "Since
bipolar disorder often emerges in late adolescence or early
adulthood, the high rates of response among bipolar depressed
patients who had early onset suggests that Symbyax may work well in
this large, well-defined population," said Robert W. Baker, M.D.,
associate medical director, USMD Neurosciences, Eli Lilly and
Company. About Bipolar Disorder Bipolar disorder typically emerges
in adolescence or young adulthood, and episodes continue
intermittently throughout life, often disrupting work, school,
family, and social life. Patients with the disease have a higher
risk of committing suicide than those with other psychiatric or
medical disorders,(1) and without effective treatment, bipolar
disorder can lead to suicide in nearly 20 percent of cases.(2) The
relative risk of suicide among patients with bipolar depression has
been shown to be nearly 35 times greater than among patients in the
manic phase of bipolar disorder.(3) Bipolar disorder, also known as
manic-depressive illness, affects an individual's mood, behavior,
and thinking. Unlike many illnesses, symptoms may be quite
different at various phases of the illness. Treatment is
challenging because some therapies that are effective for one phase
of the illness may be counterproductive for another. For example,
antidepressant treatments can precipitate manic episodes. Bipolar
disorder is a complex mental illness characterized by debilitating
mood swings ranging from episodes of deep depression (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. 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 commits
suicide. The World Health Organization estimates that bipolar
disorder is the sixth leading cause of disability in the world.
Important Information About Symbyax The most common
treatment-emergent adverse event associated with Symbyax (vs.
placebo) in clinical trials was somnolence (22 vs. 11%). Other
common events were: weight gain (21 vs. 3%), increased appetite (16
vs. 4%), asthenia (15 vs. 3%), peripheral edema (8 vs. 1%), tremor
(8 vs. 3%), pharyngitis (6 vs. 3%), abnormal thinking (6 vs. 3%),
and edema (5 vs. 0%). Contraindications -- Symbyax should not be
used with an MAOI or within at least 14 days of discontinuing an
MAOI. At least 5 weeks should be allowed after stopping Symbyax
before starting an MAOI. Thioridazine should not be given with
Symbyax or within at least 5 weeks after stopping Symbyax. Symbyax
is contraindicated in patients with known hypersensitivity to the
product or any component of the product. Hyperglycemia and diabetes
mellitus -- Hyperglycemia, in some cases associated with
ketoacidosis, coma, or death, has been reported in patients treated
with atypical antipsychotics including olanzapine alone, as well as
olanzapine taken concomitantly with fluoxetine. 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. Cerebrovascular adverse events (CVAE), including stroke,
in elderly patients with dementia -- Cerebrovascular adverse events
(e.g., stroke, transient ischemic attack), including fatalities,
were reported in patients in trials of olanzapine in elderly
patients with dementia-related psychosis. In placebo-controlled
trials, there was a significantly higher incidence of CVAE in
patients treated with olanzapine compared to patients treated with
placebo. Olanzapine is not approved for the treatment of patients
with dementia-related psychosis. Orthostatic hypotension -- Symbyax
may induce orthostatic hypotension associated with dizziness,
tachycardia, bradycardia, and in some patients, syncope, especially
during the initial dose-titration period. Particular caution should
be used in patients with known cardiovascular disease,
cerebrovascular disease, or those predisposed to hypotension.
Allergic events and rash -- In premarketing trials, the overall
incidence of rash or allergic events with Symbyax was similar to
that with placebo (4.6%, 26/571 vs. 5.2%, 25/477). In fluoxetine
clinical studies, 7% of 10,782 fluoxetine-treated patients
developed various types of rashes and/or urticaria. If rash or
other possibly allergic phenomena appear for which an alternative
etiology cannot be determined, immediate discontinuation is
recommended. Concomitant use -- Caution should be used when
prescribing medications that contain olanzapine or fluoxetine HCl
with Symbyax. Abnormal bleeding -- Patients should be cautioned
regarding the risk of bleeding associated with the concomitant use
of Symbyax with NSAIDs, aspirin, or other drugs that affect
coagulation. Mania/hypomania -- Because of the cyclical nature of
bipolar disorder, patients should be monitored closely for the
development of symptoms of mania/hypomania during treatment with
Symbyax. Prolactin and serum sodium -- As with other drugs that
antagonize dopamine receptors, Symbyax elevates prolactin levels,
and a modest elevation persists during administration; however,
possibly associated clinical manifestations were infrequently
observed. Hyponatremia has been observed in premarketing studies of
Symbyax, but the incidence of serum sodium levels occurring below
the reference range was statistically insignificant compared with
placebo (2%, 10/500 vs. 0.5%, 2/380); none of these patients had a
treatment-emergent level less than 130 mmol/L. Transient,
asymptomatic elevations of hepatic transaminase -- In premarketing
trials, statistically significant ALT (SGPT) elevations (>/= 3
times the upper limit of the normal range) were observed in 6.3%
(31/495) of patients exposed to Symbyax compared with 0.5% (2/384)
of the placebo patients and 4.5% (25/560) of olanzapine-treated
patients. None of these patients developed jaundice. Periodic
assessment of transaminases is recommended in patients with
significant hepatic disease. Weight gain -- In clinical studies,
the mean weight gain for Symbyax- treated patients was
statistically significantly greater than placebo-treated (3.6 kg
vs. -0.3 kg) and fluoxetine-treated (3.6 kg vs. -0.7 kg) patients
but was not statistically significantly different from
olanzapine-treated patients (3.6 kg vs. 3.0 kg). Fourteen percent
of Symbyax-treated patients met criterion for having gained >10%
of their baseline weight. Special populations and elderly --
Dysphagia was observed infrequently in premarketing studies, but as
with other psychotropic drugs, Symbyax should be used cautiously in
patients at risk for aspiration pneumonia. Esophageal dysmotility
and aspiration have been associated with antipsychotic drug use. In
2 clinical studies in patients with Alzheimer's disease, 2
olanzapine- treated patients died from aspiration pneumonia, with
one of these patients experiencing dysphagia. As with other
CNS-active drugs, Symbyax should be used with caution in elderly
patients with dementia. The lowest starting dose should be
considered in patients with hepatic impairment. As with all
medications that contain an antipsychotic, the following
considerations should be taken into account when prescribing
Symbyax: Neuroleptic malignant syndrome (NMS) -- as with all
antipsychotic medications, a rare condition known as NMS has been
reported with olanzapine. If signs and symptoms appear, immediate
discontinuation is recommended. Tardive dyskinesia (TD) -- as with
all antipsychotic medications, prescribing should be consistent
with the need to minimize the risk of TD. If its signs and symptoms
appear, discontinuation should be considered. Seizures -- occurred
infrequently in premarketing clinical trials (4/2066, 0.2%).
Confounding factors may have contributed to many of these
occurrences. Symbyax should be used cautiously in patients with a
history of seizures or with conditions that lower the seizure
threshold. Such conditions may be more prevalent in patients age 65
years or older. About Eli Lilly and Company Lilly, a leading
innovation-driven corporation, is developing a growing portfolio of
first-in-class and best-in-class pharmaceutical products by
applying the latest research from its own worldwide laboratories
and from collaborations with eminent scientific organizations.
Headquartered in Indianapolis, Ind., Lilly provides answers --
through medicines and information -- for some of the world's most
urgent medical needs. Additional information about Lilly is
available at http://www.lilly.com/ . This press release contains
forward-looking statements about the potential of Symbyax for the
treatment of the depressive phase of bipolar disorder and reflects
Lilly's current beliefs. However, as with any pharmaceutical
product, there are substantial risks and uncertainties in the
process of development and commercialization. There is no guarantee
that the product will prove to be commercially successful. For
further discussion of these and other risks and uncertainties, see
Lilly's filings with the United States Securities and Exchange
Commission. Lilly undertakes no duty to update forward-looking
statements. (1) Jamison, KR. "Suicide and Bipolar Disorder."
Journal of Clinical Psychiatry. 2000;61 (suppl 9). (2) National
Institute of Mental Health,
http://www.nimh.nih.gov/publicat/bipolarresfact.cfm . (3) Tohen M,
Vieta E, Calabrese J, Ketter T, Sachs G, et al. "Efficacy of
Olanzapine and Olanzapine-Fluoxetine Combination in the Treatment
of Bipolar I Depression." Arch Gen Psychiatry. 2003;60:1079-1088.
(Logo: http://www.newscom.com/cgi-bin/prnh/20031219/LLYLOGO )
http://www.newscom.com/cgi-bin/prnh/20031219/LLYLOGO DATASOURCE:
Eli Lilly and Company CONTACT: Marni Lemons of Eli Lilly and
Company, +1-317-433-8990, +1-317-997-5604 (cell)
Copyright