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Zyprexa Appears to Delay Relapse in Patients with Schizophrenia Significantly Longer Than Other Atypical Antipsychotics

Additional Evidence that Efficacy of Atypical Antipsychotics is Not Equal

INDIANAPOLIS, IN -- February 11, 2004 -- New data presented today at a major schizophrenia conference in Switzerland demonstrate that Zyprexa® (olanzapine) delays relapse significantly longer in patients with schizophrenia than other atypical antipsychotics, Eli Lilly and Company announced. The data resulted from three double-blind randomized clinical trials comparing Zyprexa with Risperdal® (risperidone), Seroquel® (quetiapine)and Geodon® (ziprasidone) for efficacy in treating patients diagnosed with schizophrenia.

Relapse, a reemergence of psychotic symptoms, can be devastating, leading to functional, social and physiological decline over the lifetime of the patient. (1) A large review of the literature indicated that 42 percent of patients with schizophrenia relapsed over the course of a year. For patients who discontinued antipsychotic therapy, relapse was an almost certainty at one year.(2) Additionally, some studies have found that patients on continuous drug therapy have less change in their brain structure than those patients not on medication. (3)

"For patients with schizophrenia, there is a high risk of relapse, but the frequency and severity of its effects can be managed," said Jeffery Lieberman, M.D., Vice Chairman of Psychiatry, Professor of Psychiatry and Pharmacology, University of North Carolina School of Medicine "In order for physicians to help patients attain stability and realize individual potential, an effective treatment must delay the recurrence of relapse and promote treatment adherence. Based on these trials, olanzapine is shown to be a promising choice to achieve both treatment goals"

Study Details
Post-hoc analyses were conducted on three randomized, double-blind studies comparing Zyprexa to risperidone for 28 weeks, to ziprasidone for 28 weeks, and to quetiapine for 24 weeks.

The analyses looked at those patients who had improved by 20 percent or 30 percent in the total Positive and Negative Syndrome Scale (PANSS-total) score after 8 weeks. The PANSS is used in clinical trials to rate symptoms in schizophrenia such as hallucinations, delusions, disorganized thought and lack of motivation. Relapse was then defined for those patients between 8 weeks and the end of the study as a 20 percent or 30 percent worsening in PANSS-total scores and a Clinical Global Impressions Severity of Illness (CGI severity) score >= 3. Four levels of response/relapse comparisons (20/20, 20/30, 30/20, 30/30) were made for each treatment pair.

Over the course of each trial, Zyprexa-treated patients relapsed significantly less than patients treated with risperidone, quetiapine and ziprasidone across all four levels of response and relapse.

Additional findings from the studies also show that patients treated with Zyprexa stay on their medication longer than those treated with the other atypical antipsychotic therapies. In an analysis of all the patients in the trials, Zyprexa-treated patients show significantly higher study completion rates than patients treated with quetiapine (52% vs. 38%; p<0.05) and ziprasidone (60% vs. 42%; p<0.05). An analysis of patients who responded by greater than 30 percent in the PANSS total at 8 weeks indicated that Zyprexa-treated patients show significantly higher completion rates than patients treated with risperidone (81% vs. 59%; p<0.001) and quetiapine (89% vs. 62%; p<0.05).

"Schizophrenia is a lifelong illness requiring lifelong treatment," said Bruce Kinon, M.D., Medical Advisor, US Medical Neurosciences, Eli Lilly and Company. "Physicians are looking for treatments, like Zyprexa, that patients are more likely to continue as prescribed by their clinicians, to help combat the cycle of relapse, thus helping their patients move forward with their lives."

About Schizophrenia
Schizophrenia is a severe and debilitating disease often characterized by acute episodes of delusions (false beliefs that cannot be corrected by reason), hallucinations (usually in the form of voices) and long-term impairments such as diminished emotion, lack of interest, and depressive signs and symptoms. It is usually associated with a disruption in social and familyrelationships.

Schizophrenia is a common severe mental illness. There are as manyas 50 million people with schizophrenia worldwide, more than 33 million of them in developing countries. Symptoms of schizophrenia usually begin to appear in the teenage years or early to mid-twenties.

Zyprexa Background
Zyprexa is indicated in the United States for the short-term and long-term treatment of schizophrenia, for maintenance in the treatment of bipolar disorder, and either alone or in combination with lithium or valproate (Depakote®, Abbott) for the short-term treatment of acute mixed or manic episodes associated with bipolar disorder. Since Zyprexa was introduced in 1996, it has been prescribed to more than 12.5 million people worldwide.

The most common treatment-emergent adverse event associated with Zyprexa in placebo-controlled, short-term schizophrenia and bipolar mania trials was drowsiness. Other common events were dizziness, weight gain, personality disorder (COSTART term for nonaggressive objectionable behavior), constipation, restlessness, episodes of low blood pressure, dry mouth, weakness, upset stomach, increased appetite, and tremor. A small number of patients experienced asymptomatic elevations of certain liver enzymes; none of these patients experienced jaundice.

Hyperglycemia, in some cases associated with ketoacidosis, coma, or death, has been reported in patients treated with atypical antipsychotics including Zyprexa. Assessment of the relationship between atypical antipsychotic use and glucose abnormalities is complicated by the possibility of an increased background risk of diabetes mellitus in patients with schizophrenia and the increasing incidence of diabetes mellitus in the general population. The available data are insufficient to provide reliable estimates of differences in hyperglycemia-related adverse event risk among the marketed atypical antipsychotics. 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.

Prescribing should be consistent with the need to minimize the risk of neuroleptic malignant syndrome, tardive dyskinesia, seizures and low blood pressure.

In short-term (six-week) acute bipolar mania trials in combination with lithium or valproate, the most common treatment emergent adverse event associated with Zyprexa and lithium or valproate was dry mouth. Other common events were weight gain, increased appetite, dizziness, back pain, constipation, speech disorder, increased salivation, amnesia and abnormal burning or tingling of the skin.

Although the efficacy of Zyprexa in elderly patients with dementia has not been established in clinical trials and Zyprexa is not approved for use in this patient population, it is important to note the label for Zyprexa includes a warning for elderly patients with dementia. The warning states that strokes or mini-strokes (also called transient ischemic attacks or TIAs), including fatalities were reported in elderly patients with dementia-related psychosis participating in Zyprexa clinical trials.

Full prescribing information is available at www.zyprexa.com.

References:
1. Montero, I., Pérez, I. Ruiz, & Gómez-Beneyto, M. (1998). Social adjustment in schizophrenia: Factors predictive of short-term social adjustment in a sample of schizophrenic patients. Acta Psychiatrica Scandinavica, 97, 116-121.
2. Weiden, P.J., and Olfson, M. (1995). Cost of relapse in schizophrenia. Schizophrenia Bulletin, 24, 419-429.
3. Lieberman, J., Chakos, M., Wu, H., Alvir, J., Hoffman, E., Robinson, D., & Bilder, B. (2001). Longitudinal study of brain morphology in first episode schizophrenia. Biological Psychiatry, 49, 487-499.


SOURCE: GCI Group

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