NEW RESEARCH SUGGESTS OLANZAPINE IMPROVES MANIC SYMPTOMS
PR Wire
June 2, 1998, 6:13 a.m. PT
Among Patients with Bipolar Disorder
INDIANAPOLIS, June 2 /PRNewswire/ -- New data presented today at the
American Psychiatric Association annual meeting in Toronto, Canada, indicate
that olanzapine significantly improved manic symptoms among bipolar disorder
patients with acute manic or mixed episodes.
"Olanzapine has shown significant efficacy in the treatment of acute manic
or mixed episodes of bipolar disorder. Importantly, in this study olanzapine
was as effective in treating manic symptoms with psychosis as manic symptoms
without psychosis," said Mauricio Tohen, M.D., Dr.P.H., lead Lilly
investigator for the study.
Bipolar disorder, also known as manic-depressive illness, is a complex
mental illness in which patients experience extreme swings in mood from
episodes of euphoria and irritability to episodes of melancholia and
hopelessness, often with periods of normal mood in between. Many persons with
bipolar disorder experience side effects from medication, which, in turn,
effect patient compliance, and ultimately, patient outcomes.
"Olanzapine has already demonstrated its safety and efficacy in patients
with schizophrenia. This new data shows that olanzapine may be effective in
treating mania, giving patients and physicians a new treatment choice for a
very serious -- and often undertreated -- disease," said Susan McElroy, M.D.,
director of the biological psychiatry program, University of Cincinnati,
College of Medicine, and one of the investigators of the study. "Olanzapine
appears to have not only antipsychotic benefits but antimanic as well," she
added.
Due to high prevalence in the general population, bipolar disorder is not
only devastating for patients and their families, but is also a great economic
drain on society. It is classified as one of the top ten leading causes of
disability by the World Health Organization. In addition, suicide rates are
also high among people who suffer from bipolar disorder -- an estimated 25
percent of bipolar disorder sufferers attempt suicide.
"Far too many patients have attempted to take their lives because they
aren't receiving adequate treatment or have difficulty complying with
treatment," said McElroy.
Study Design
A randomized, double-blind, placebo-controlled study was conducted
comparing the efficacy and safety of olanzapine versus placebo in the
treatment of acute mania or mixed episodes in 139 patients (olanzapine=70,
placebo=69). Patients meeting the DSM-IV (32) diagnostic criteria for bipolar
disorder (manic or mixed, with or without psychotic features) were treated for
a period of three weeks, followed by open label extension up to one year.
Patients began double-blind therapy with either olanzapine 10 mg/day or
placebo once per day. The dose could be adjusted up or down, as clinically
indicated, in 5 mg increments within the allowed dose range of 5-20 mg/day.
Mean modal dose for olanzapine during the three-week acute phase was 14.9
mg/day. Treatment groups did not differ with regard to baseline patient
characteristics or severity of illness rating scores.
Change from baseline to endpoint (LOCF) on the Young-Mania Rating Scale
(Y-MRS) was the primary efficacy measure. A clinical response was defined a
priori as >50 percent decrease from baseline on the total Y-MRS total score.
Quality of life was measured using the SF-36 Scale. The Hamilton Psychiatric
Rating Scale for Depression 21 item (HAMD-21) was used to measure depressive
symptoms.
Study Findings
Efficacy
The olanzapine-treatment group experienced a statistically significantly
greater mean improvement in Y-MRS total score than the placebo-treatment group
(-10.26 and -4.88, respectively, p=.019). Based on the clinical response
criteria, statistically significantly more olanzapine-treatment patients
(34/70, 48.6 percent) responded than those assigned to placebo (16/66, 24.2
percent; p=.004).
Furthermore, olanzapine showed a rapid onset of action, with approximately
81 percent of the improvements observed in the mean Y-MRS total score achieved
after the first week of treatment. There was no statistically significant
difference between the two treatment groups in the frequency of use of
anticholinergics prescribed for extrapyramidal syndrome (EPS).
The analysis of mean change from baseline to endpoint in HAMD-21 total
scores showed no statistically significant treatment advantages in depressive
symptom improvement between treatment groups. In addition, treatment with
olanzapine was not associated with a significant baseline to endpoint
worsening in HAMD-21 scores relative to placebo.
Quality of Life
Olanzapine-treated patients had a statistically significantly greater
improvement in their physical functioning than placebo-treated patients as
measured by the SF-36 physical functioning subscore (olanzapine 4.01, placebo
-1.84, p=.016). No other SF-36 subscore was statistically significantly
different between treatment groups over the three-week acute phase.
Safety
The following adverse events were reported significantly more frequently
in the olanzapine group than in the placebo group: somnolence, dry mouth,
dizziness and weight gain. No patients discontinued therapy because of an
adverse event, while two placebo-treated patients discontinued therapy for
such a reason. There was also no statistically significant difference in the
incidence of extra-pyramidal side effects (EPS) between olanzapine and
placebo. The laboratory measurements such as ALT/SGPT and vital sign
measurements were consistent with observations from earlier studies with
olanzapine.
Olanzapine is indicated in the United States for the management of the
symptoms of psychotic disorders as demonstrated in clinical trials with
schizophrenia patients. Lilly's application for the use of olanzapine in
bipolar mania is currently under review by the U.S. Food and Drug
Administration.
Lilly is a global research-based pharmaceutical corporation headquartered
in Indianapolis, Ind., that is dedicated to creating and delivering innovative
pharmaceutical-based health care solutions that enable people to live longer,
healthier and more active lives.
SOURCE Eli Lilly and Company
-0- 06/02/98
/CONTACT: Theresa Owens of Eli Lilly, 317-276-3254/
/Company News On-Call: prnewswire.com or fax, 800-758-5804,
ext. 126236/
/Web site: lilly.com
|
