First Head-to-Head Study Shows Patients with Bipolar Depression Had Greater Symptom Improvement on Olanzapine and Fluoxetine HCl
May 24 2005 - 12:00PM
PR Newswire (US)
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,
+1-212-537-8261; or Heather Lusk of Eli Lilly and Company,
+1-317-433-5600
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