Studies Show Schizophrenia Patients Taking Atypicals Stayed on Treatment Longer Than Patients Taking Older, Typical Antipsychotics

SAVANNAH, Ga., April 6 /PRNewswire-FirstCall/ -- Findings from three studies show that patients taking atypical antipsychotics stayed on their medication longer than older, typical antipsychotics when comparing time to all-cause medication discontinuation. The studies were presented this week at a major international psychiatric congress in Savannah, Ga.

One of the studies revealed that patients taking olanzapine or clozapine remained on treatment longer than other atypicals (risperidone, quetiapine, ziprasidone) or the typical perphenazine. Another study demonstrated that longer time to trial discontinuation appeared to be associated with significantly greater improvements in symptoms and quality of life as measured by standard psychiatric measures. Pearson partial correlations were used to assess the relationships between the length of time patients stayed in the trial and changes in symptoms [as measured by PANSS scores (Positive and Negative Syndrome Scale)] and health-related quality of life (e.g., Medical Outcomes Study 36-Item Short Form Health Survey, SF-36; Heinrichs-Carpenter Quality of Life Scale, QLS).

Key Findings
"When we observed a highly diverse group of patients with schizophrenia undergoing treatment in real-world settings, we found that patients taking the atypical antipsychotics clozapine or olanzapine had a consistently and significantly longer time to medication discontinuation compared to patients treated with perphenazine and other typical antipsychotics," said Haya Ascher- Svanum, Ph.D., senior research scientist, U.S. Outcomes Research, Eli Lilly and Company. "The results were consistent across many diverse systems of care in both urban and rural environments regardless of gender, age and ethnicity."

In a retrospective integrated-analysis of 15 randomized, double-blind, head-to-head, published or presented clinical trials, researchers used weighted mean hazard ratios to determine the risk of discontinuation of other antipyschotics compared to olanzapine based on pooled data. The findings suggest that patients treated with olanzapine had a significantly greater likelihood of continuing treatment when compared to haloperidol, risperdone and ziprasidone. Olanzapine was also found to have greater treatment duration than quetiapine in a single study comparison. Kaplan-Meier estimators for probability of staying on treatment were obtained for each of the studies. The analysis was limited by the variable length of the studies, which ranged from 12 weeks to 104 weeks. All studies were from clinical, controlled trials, not naturalistic, open-label studies.

Among the findings, researchers concluded that when compared to olanzapine:
* Patients treated with haloperidol had a 40 percent greater risk of discontinuing treatment.
* Patients treated with risperidone had a 30 percent greater risk of discontinuing treatment.
* Patients treated with ziprasidone had a 60 percent greater risk of discontinuing treatment.
* Patients treated with quetiapine had a 40 percent greater risk of discontinuing treatment.

About Olanzapine Olanzapine (Zyprexa(R), Eli Lilly and Company) is indicated for the treatment of schizophrenia, for acute bipolar mania, and for maintenance treatment in bipolar disorder.

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.

The most common treatment-emergent adverse event associated with Zyprexa in combination with lithium or divalproex in 6-week combination bipolar mania trials was dry mouth. Other common events were weight gain, increased appetite, dizziness, back pain, constipation, speech disorder, increased salivation, amnesia, and paresthesia.

Hyperglycemia and diabetes mellitus -- 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. 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.

Safety experience in elderly patients with dementia-related psychosis -- In placebo-controlled clinical trials of elderly patients with dementia- related psychosis, the incidence of death in olanzapine-treated patients was significantly greater than placebo-treated patients (3.5% vs. 1.5%, respectively). Risk factors that may predispose this patient population to increased mortality when treated with Zyprexa include age >80 years, sedation, concomitant use of benzodiazepines, or presence of pulmonary conditions (e.g., pneumonia, with or without aspiration). Zyprexa is not approved for the treatment of patients with dementia-related psychosis.

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 Zyprexa in elderly patients with dementia-related psychosis. In placebo-controlled trials, there was a significantly higher incidence of CVAE in patients treated with Zyprexa compared to patients treated with placebo. Zyprexa is not approved for the treatment of patients with dementia-related psychosis.

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

Full prescribing information is available at http://www.zyprexa.com .

This press release contains forward-looking statements about the potential of Zyprexa for the treatment of schizophrenia 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 continue 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) Gilmer TP, Dolder CR, Lacro JP, Folsom DP, Lindamer L, et al. "Adherence to Treatment With Antipsychotic Medication and Health Care Costs Among Medicaid Beneficiaries With Schizophrenia." Am J Psychiatry 2004 161: 692-699.

(2) Lehman AF, Lieberman JA, Dixon LB, McGlashan TH, Miller AL, Perkins DO, Kreyenbuhl J; American Psychiatric Association; Steering Committee on Practice Guidelines. Practice guideline for the treatment of patients with schizophrenia, second edition. Am J Psychiatry 2004 Feb;161(2 Suppl):1-56. Contact: Michael Monheit, Esquire, Monheit Law, PC
Zyprexa: Lawyer: Side Effects: Diabetes