CATIE Phase 2 Data Confirm Patients Stay on Treatment Longer Because of Symptom Improvement More So Than Tolerability
02 April 2006 - 1:00AM
PR Newswire (US)
Zyprexa Was Among Most Effective Atypical Antipsychotics Studied
INDIANAPOLIS, April 1 /PRNewswire-FirstCall/ -- Eli Lilly and
Company today commented on findings of the phase 2 CATIE (Clinical
Antipsychotic Trial of Intervention Effectiveness) trial and
provided perspective on Zyprexa's overall results. The findings
from phase 2 were published in the April issue of the American
Journal of Psychiatry. CATIE phase 2 focused on the use of atypical
antipsychotics to treat chronic schizophrenia and was designed to
evaluate which ones were better "rescue" treatments for patients
who required a medication switch in phase 1 either because the
prior medication didn't work well enough or they were not able to
tolerate it. This was measured by medication discontinuation for
any cause. Results indicated that patients continue medication
treatment longer when given a medication that effectively controls
their psychotic symptoms, and that when patients switch
medications, it is more often due to the drug's lack of efficacy
rather than the patient's ability to tolerate the drug. "Results
from CATIE phase 1 and 2 challenge the notion that patients
discontinue their medication mainly due to side effects," said J.
Steven Lamberti, M.D., associate chair for clinical programs,
department of psychiatry, University of Rochester Medical Center
and CATIE investigator. "These findings further demonstrate the
need for doctors to fully evaluate the benefit/risk profiles of
atypical antipsychotics and why individualized treatment is so
important to consider when treating chronic schizophrenia."
Zyprexa(R) (olanzapine) was among the most effective atypical
antipsychotics studied in the second phase of CATIE for those
patients who required a medication change in Phase 1. In the
efficacy arm, clozapine performed best in terms of all-cause
discontinuation, followed by Zyprexa(i). In the tolerability arm,
risperidone and Zyprexa performed best in terms of all-cause
discontinuation, which was contrary to the study's hypothesis that
ziprasidone would be the most effective atypical because it caused
little or no weight gain(ii). In addition, a secondary analysis in
the tolerability arm of the study showed a statistically
significant reduction in positive psychotic symptoms (such as
paranoid ideas or hearing voices) for patients taking Zyprexa.
Zyprexa patients also had the lowest rate of hospitalizations (11
percent) among the other atypicals studied (risperidone (15
percent), ziprasidone (16 percent), and quetiapine (20
percent)(iii)). These findings are consistent with CATIE phase 1.
While there were no statistical differences among those who
discontinued treatment because of intolerability among the four
atypical antipsychotics studied in this arm, there were variations
in the types of adverse events reported. Zyprexa patients in phase
2 experienced greater weight gain and increases in total
cholesterol and triglyceride levels versus patients using the other
atypical antipsychotics studied. These results are similar to data
reported in phase 1. (Information about adverse events related to
increases in blood glucose levels, lipid metabolism and weight gain
is included in the Zyprexa product label.) "Results of this
landmark study confirm that efficacy matters when treating this
devastating illness," said Robert Baker, M.D., medical director,
U.S. neuroscience, Eli Lilly and Company. "Studies such as CATIE
are important for both doctors and patients as they provide
insights about why patients continue or discontinue their
medication treatment. This is important because patients who stay
on their treatment longer may have a lower risk of relapse as well
as experience fewer hospitalizations. "Schizophrenia is a very
complex neurological disorder," he added. "For reasons we do not
yet fully understand, a medication that works in one person with
schizophrenia may not work in another. It's important for doctors
and patients to have access to a variety of medications, and it's
crucial for patients to stay on the medication that works best for
them." CATIE Background CATIE was designed to evaluate the overall
clinical effectiveness of antipsychotics in the treatment of
schizophrenia, as measured by any-cause medication discontinuation,
a measure that integrates both the patients' and the doctors'
judgment of how well a medication works, its safety and how well
the patient tolerates the treatment. If patients were experiencing
issues with efficacy or tolerability on the medication they were
randomized to in phase 1, they could decide with their doctors to
switch medications and enroll in phase 2. In this "rescue" phase,
patients could choose to enroll in the efficacy arm or the
tolerability arm. In the efficacy arm, they received clozapine or
were reassigned to double- blind treatment with a different
atypical antipsychotic -- olanzapine, quetiapine or risperidone. In
the tolerability arm, they were randomized to receive ziprasidone
or one of the same three atypical antipsychotics used in the
efficacy arm. Patients were given a different atypical
antipsychotic than the one they received in phase 1. Time to
all-cause discontinuation was measured in each study arm.
Zyprexa(R) Background Zyprexa(R) (olanzapine) is indicated in the
United States for the short- and long-term treatment of
schizophrenia, acute mixed and manic episodes of bipolar I
disorder, and maintenance treatment of bipolar disorder. Since
Zyprexa was introduced in 1996, it has been prescribed to more than
18 million people worldwide. Zyprexa is not approved for the
treatment of patients with dementia- related psychosis. Elderly
patients with dementia-related psychosis treated with atypical
antipsychotic drugs are at an increased risk of death compared with
those patients taking a placebo. In addition, compared to elderly
patients with dementia-related psychosis taking a placebo, there
was a significantly higher incidence of cerebrovascular adverse
events in elderly patients with dementia-related psychosis treated
with Zyprexa. Hyperglycemia, in some cases extreme and associated
with ketoacidosis or hyperosmolar coma or death, has been reported
in patients treated with atypical antipsychotics, including
Zyprexa. Prescribing should be consistent with the need to minimize
the risk of neuroleptic malignant syndrome, tardive dyskinesia,
seizures and orthostatic hypotension. The most common
treatment-emergent adverse event associated with Zyprexa in
placebo-controlled, short-term schizophrenia and bipolar mania
trials was somnolence. Other common events were dizziness, weight
gain, personality disorder (COSTART term for nonaggressive
objectionable behavior), constipation, akathisia, postural
hypotension, dry mouth, asthenia, dyspepsia, increased appetite and
tremor. Full prescribing information, including a boxed warning, is
available at http://www.zyprexa.com/. 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/ .
P-LLY (i) McEvoy, Joseph P., Joseph P., Lieberman, Stroup, Scott T.
"Effectiveness of Clozapine Versus Olanzapine, Quetiapine, and
Risperidone in Patients with Chronic Schizophrenia Who Did Not
Respond to Prior Atypical Antipsychotic Treatment" Am J Psychiatry
2006 163: 600-610 (ii) Stroup, Scott T., Joseph P., Lieberman,
McEvoy, Joseph P. "Effectiveness of Olanzapine, Quetiapine,
Risperidone, and Ziprasadine in Patients with Chronic Schizophrenia
Following Discontinuation of a Previous Antipsychotic" Am J
Psychiatry 2006 163: 611-622 (iii) Stroup, Scott T., Joseph P.,
Lieberman, McEvoy, Joseph P. "Effectiveness of Olanzapine,
Quetiapine, Risperidone, and Ziprasadine in Patients with Chronic
Schizophrenia Following Discontinuation of a Previous
Antipsychotic" Am J Psychiatry 2006 163: 611-622 (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: Carole Puls, +1-317-277-1421,
+1-317-612-4859 (cell), Carole Copeland, +1-317-277-3661,
+1-317-610-6196 (cell), both of Eli Lilly and Company
Copyright