ELi Lilly and Company announced today that the US Food and Drug Administration has approved Zyprexa® (olanzapine) for long-term therapy and maintenance of treatment response of schizophrenia. Zyprexa is the first of the newer generation of antipsychotics, known as "atypicals," to prove its long-term effectiveness in
Schizophrenia is a brain disorder often characterized by acute episodes of
delusions (false beliefs that cannot be corrected by reason), and
hallucinations (usually in the form of non-existent voices) and long-term
impairments such as diminished emotion, lack of interest and depressive signs
Approximately 2.5 million Americans, ages 18-25 have schizophrenia, and
more than 100,000 new cases are reported each year.
"Zyprexa demonstrated robust efficacy and long-term safety in the study
comparing it with placebo in the maintenance of treatment response in
schizophrenia," said Alan Breier, M.D., Research Fellow and Leader, Zyprexa
Product Team, Lilly Research Laboratories. "In fact, the results of the study
were so strong, we were ethically bound to the early termination of the study
to limit unnecessary patient exposure to placebo."
Placebo-treated patients were almost 10 times as likely to relapse over a
six-month period compared to the Zyprexa-treated patients. The six-month
cumulative relapse rate for Zyprexa was statistically superior to placebo (6%
versus a placebo rate of 55%, p<.0001).
"Schizophrenia is a lifelong illness requiring lifelong treatment," said
Ralph Aquila, M.D., Director, Residential Community Services, Saint Luke's-
Roosevelt Hospital Center. "I can't overestimate the value of a medication
with proven long-term efficacy and safety, because it can prevent the need to
switch medications. It's best to keep a patient on one medication for as long
as possible, because treatment changes can often lead to symptom relapse."
Relapse can also occur when patients no longer respond to medication, fail
to take their medication as prescribed, are under more stress than usual, do
not get enough rest, drink alcohol or use street drugs. Patients experiencing
relapse have described feeling nervous or afraid, having trouble sleeping,
hearing voices in their head getting louder, and feeling like they are
slipping back into their illness.
The FDA's approval of Zyprexa as the first atypical antipsychotic in the
US to receive an indication for maintenance of treatment response of
schizophrenia was based on results of a double-blind placebo-controlled
discontinuation study of 326 clinically stable outpatients with few or no
symptoms for at least six weeks. They received oral Zyprexa therapy for
another six weeks followed by an eight-week observation period to confirm
Following the observation period, 224 patients were randomized to Zyprexa
(10-20 mg/day) and 102 patients were randomized to placebo. There were 177
patients with schizophrenia (79%) and 47 with schizoaffective disorder (21%)
in the Zyprexa group. There were 89 patients with schizophrenia (87.3%) and
13 with schizoaffective disorder (12.7%) receiving placebo.
"Zyprexa-treated patients were significantly less likely to discontinue
treatment as a result of either an adverse event or because of lack of
efficacy," Dr. Breier said. "The Zyprexa treated group also improved on all
quality of life measures while those on placebo worsened. We found that
Zyprexa was safe and generally well-tolerated at doses of 10, 15 or 20
The label change for maintenance of treatment response in patients with
schizophrenia is the second new indication received for Zyprexa in the United
States this year. On March 17, the FDA approved Zyprexa for marketing for the
short-term treatment of acute manic episodes associated with bipolar disorder.
Zyprexa is indicated in the United States for the treatment of
schizophrenia. It is also approved for the short-term treatment of acute
manic episodes associated with bipolar disorder. Since Zyprexa was introduced
in 1996, it has been prescribed to more than 5 million people worldwide.
In the original schizophrenia registration trials, Zyprexa was generally
well tolerated. However, as with all medications, Zyprexa was associated with
some side effects. In the original six-week, acute-phase schizophrenia
trials, the most common treatment-emergent adverse event associated with
Zyprexa was somnolence. Other common events were dizziness, weight gain,
constipation, akathisia (restlessness) and postural hypotension. Modest
elevations of prolactin were also seen, although mean changes from baseline to
endpoint were not statistically significantly different between Zyprexa and
placebo. A small number of patients experienced asymptomatic elevations of
hepatic transaminase; none of these patients developed jaundice or drug-
In short-term (3- and 4-week) acute bipolar mania trials, the most common
treatment-emergent adverse event associated with Zyprexa was somnolence.
Other common events were dry mouth, dizziness, asthenia, constipation,
dyspepsia, increased appetite and tremor.