First Head-to-Head Study Shows Patients with Bipolar Depression Had Greater Symptom Improvement on Olanzapine and Fluoxetine HCl

First Head-to-Head Study Shows Patients with Bipolar Depression
Had Greater Symptom Improvement on Olanzapine and Fluoxetine HCl Capsules than
Lamotrigine 


ATLANTA, May 24  /PRNewswire-FirstCall/ -- New data from the first head-to-
head study comparing olanzapine and fluoxetine HCl capsules (OFC) and
lamotrigine for the treatment of bipolar depression, show that patients treated
with OFC experienced significantly greater improvement in both depressive and
manic symptoms associated with bipolar depression than patients treated with
lamotrigine.  Additionally, results show that patients treated with OFC
responded more quickly to therapy than patients treated with lamotrigine. 
These findings were presented today at the annual meeting of the American
Psychiatric Association.

Lamotrigine is not indicated for the acute treatment of bipolar depression;
rather, it is indicated for the maintenance of bipolar I disorder to delay the
time to occurrence of mood episodes (depression, mania, hypomania, mixed
episodes) in patients treated for acute mood episodes with standard therapy. 
The effectiveness of lamotrigine in the acute treatment of mood episodes has
not been established.

OFC is the first and only acute treatment approved by the U.S. Food and Drug
Administration (FDA) for the depressive phase of bipolar disorder, a
notoriously difficult-to-treat condition that afflicts millions of Americans.
People with bipolar disorder typically spend an average of one-third of their
lives in the depressive phase and take longer to recover from it.  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)  However OFC is not indicated for the treatment of bipolar mania
or bipolar maintenance.

"Bipolar depression is a devastating and debilitating condition that can wreak
havoc on all aspects of a person's emotional, financial and social life, and
often leads patients to take their own lives," said Doug Williamson, M.D.,
MRCPsych, US Medical Advisor, Eli Lilly and Company.  "Providing symptom relief
quickly is crucial in helping patients with bipolar depression."

Key Findings

In the double-blind 7-week trial, patients suffering from an acute episode of
bipolar I depression were randomized to treatment with OFC (6/25, 6/50, 12/25,
or 12/50 mg/day, n=205) or lamotrigine (200 mg/day; n=205).   Patients were
titrated to clinically effective doses as instructed by the products' labeling.
 Efficacy measures of improvement in both depressive and manic symptoms
associated with bipolar depression included Clinical Global Impression Severity
(CGI-S) as the primary outcome measure, as well as Montgomery-Asberg Depression
Rating Scales (MADRS) and Young-Mania Rating Scale (YMRS).

Results showed:

*  Patients treated with OFC had greater improvement than lamotrigine- treated
patients across the 7-week treatment period when measuring CGI- Severity
(p=0.002), MADRS total score (p=0.002) and YMRS (p=0.001);

*  Time to response (50 percent decrease in MADRS scores) was significantly
(p=0.010) shorter for patients treated with OFC.

In the study, serious adverse events, including symptoms associated with mania,
occurred more frequently in patients treated with lamotrigine (5.4 percent vs.
1.0 percent; p=.012).  Non-serious adverse events occurred more frequently (p <
.05) with OFC treatment, including somnolence, weight gain and dry mouth.

About Bipolar Disorder

Bipolar disorder, sometimes referred to as manic depression, is a complex
mental illness characterized by extreme and debilitating mood swings.  These
swings or "highs and lows" can range from episodes of deep depression marked by
feelings of extreme guilt, sadness, anxiety, and, at times, thoughts of
suicide; to episodes of mania (abnormal euphoria, elation and irritability)
interspersed with periods of normal mood.  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 bipolar disorder may
be counterproductive for another.  For example, antidepressant treatments 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.  The World Health
Organization estimates that bipolar disorder is the sixth leading cause of
disability in the world.

Important Information About Olanzapine-Fluoxetine HCl

Antidepressants increased the risk of suicidal thinking and behavior
(suicidality) in short-term studies in children and adolescents with major
depressive disorder (MDD) and other psychiatric disorders.  Patients started on
therapy should be observed closely for clinical worsening, suicidality, or
unusual changes in behavior.  OFC is not approved for use in pediatric
patients.

Elderly patients with dementia-related psychosis treated with atypical
antipsychotic drugs are at an increased risk of death compared to placebo. OFC
is not approved for the treatment of elderly patients with dementia- related
psychosis.

The most common treatment-emergent adverse event associated with OFC (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 -- OFC 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 OFC before starting an MAOI.  Thioridazine should not be given with
OFC or within at least 5 weeks after stopping OFC.  OFC 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 -- OFC 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 OFC 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 OFC.

Abnormal bleeding -- Patients should be cautioned regarding the risk of
bleeding associated with the concomitant use of OFC 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 OFC.

Prolactin and serum sodium -- As with other drugs that antagonize dopamine
receptors, OFC 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 OFC, 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 OFC 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 OFC-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 OFC-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, OFC 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, OFC 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 OFC:

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.
OFC 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.

For prescribing information please visit http://www.lilly.com/. P-LLY

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
Olanzapine and Fluoxetine HC1 capsules 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:  Kerry Dixon of GCI Group, [phone]; or Heather Lusk of

Eli Lilly and Company, [phone]

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