Symbyax(TM) Shown to Reduce Symptoms Associated With Suicidal Thinking in Patients With Bipolar Depression

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.

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DATASOURCE: Eli Lilly and Company



CONTACT:  Marni Lemons of Eli Lilly and Company, [phone],

[phone] (cell)

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