Eli Lilly and Company: Results of Landmark Schizophrenia Study Show Patients Treated with Olanzapine Demonstrated Better Adheren

    Eli Lilly and Company

Medication Adherence Associated with Improved Long-term Outcomes

Patients with schizophrenia treated with olanzapineare significantly
more likely to adhere to their medication and stay on their medication
for a longer duration compared to patients receiving risperidone,
quetiapine or haloperidol, new data show. The findings were presented
at the 55th Institute on Psychiatric Services meeting in Boston and
were collected as part of a landmark, three-year "real world" study of
schizophrenia, called the Schizophrenia Care and Assessment Program
(SCAP) that evaluated currently available schizophrenia treatments.

Additionally, SCAP researchers found that higher rates of adherence
with medication were associated with improved long-term outcomes,
including improved mental functioning, improved satisfaction with
interpersonal relationships, decreased likelihood of hospitalization,
and better overall life satisfaction.

"People with schizophrenia have a high likelihood of discontinuing
their medication at some point, which can wreak havoc on a person's
life because, without medication, many patients will relapse or
require hospitalization," said Marvin Swartz, M.D., professor and head
of the Division of Social and Community Psychiatry at Duke University
Medical Center, a lead SCAP investigator. "These data are important
because they demonstrate a greater likelihood of medication adherence
with olanzapine and several other studies confirm that adherence to
medication is associated with improved prognosis, symptom control, and
a better quality of life over time."

Unlike a traditional clinical trial, SCAP was a longitudinal
observational study designed to understand and improve the treatments
currently provided to schizophrenia patients in usual care settings
(e.g., employment, mental and physical functioning, housing and
substance abuse). Sponsored by Eli Lilly and Company, SCAP is one of
the largest naturalistic studies ever to be conducted in the United
States, consisting of 2,400 patients located at multiple centers
across the country.

Key Findings

In this non-randomized, naturalistic prospective study (SCAP),
medication adherence was investigated in patients who were newly
initiated on olanzapine (390 patients), risperidone (287 patients),
quetiapine (133 patients), and haloperidol (154 patients). The
patients in these four treatment groups were compared on the level of
adherence and persistence with their medications during the one year
following treatment initiation.

-- Adherence to treatment, as measured by the medication possession
ration (MPR; the total days with the target medication divided by 365
days) was significantly higher with olanzapine (0.75) than with
risperidone (0.69), quetiapine (0.61) or haloperidol (0.49).

-- Olanzapine-treated patients stayed on their medication
significantly longer than patients receiving risperidone, quetiapine
or haloperidol. Average time to all-cause discontinuation was 260.1
days for olanzapine, 236.8 days for risperidone, 211.8 days for
quetiapine, and 154.1 days for haloperidol.

In a comparison of five antipsychotics, which included clozapine,
patients treated with olanzapine or clozapine stayed on their
medication significantly longer than patients receiving risperidone,
quetiapine or haloperidol. Compared to olanzapine, the likelihood of
discontinuation was 26 percent greater among patients receiving
risperidone, 54 percent greater among patients receiving quetiapine,
and 158 percent greater among patients receiving haloperidol. However,
the clozapine-treated group was 46 percent less likely to discontinue
medication than olanzapine-treated patients. A total of 1,054 patients
were included in this study subset.

A two-year follow up of 1,677 patients was also conducted to assess
the relationship between medication adherence and long-term
functional, quality of life and core symptom outcomes among
schizophrenia patients. Greater adherence to medications was
associated with fewer legal problems and hospitalizations, improved
depressive symptoms, satisfaction with interpersonal relationships,
overall mental health, and life satisfaction.

Study Design

All study participants had been diagnosed with schizophrenia,
schizoaffective disorder, or schizophreniform disorder. Adherence was
calculated using the medication possession ration (MPR), the total
days with the target medication divided by 365 days. Time to all-cause
discontinuation of an antipsychotic during the year following its
initiation was measured by the total number of days on the
antipsychotic, and the number of days of continuous treatment up to
the first gap in treatment of more than 14 days.

"An observational study such as SCAP provides an innovative research
model because it evaluates and demonstrates the effectiveness of a
treatment in a real-world setting," said Dr. Swartz. "This type of
outcomes data offers unique advantages that differentiate it from
randomized clinical trials. Results of SCAP demonstrate superior
adherence with olanzapine and which may well be a result of
olanzapine's efficacy and tolerability profile."

About Schizophrenia

Schizophrenia is a severe and debilitating psychosis often
characterized by acute episodes of delusions (false beliefs that
cannot be corrected by reason), hallucinations (usually in the form of
non-existent 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 family
relationships.

Schizophrenia is the most common severe mental illness. More than two
million American adults have the disease, with more than 100,000 new
cases reported each year. Symptoms of schizophrenia usually begin to
appear in the teenage years or early to mid-twenties.

Olanzapine Background

Olanzapine is indicated in the United States for the treatment of
schizophrenia, the short-term treatment of acute manic episodes
associated with bipolar disorder and for the long-term therapy and
maintenance of treatment response of schizophrenia. Since olanzapine
was introduced in 1996, it has been prescribed to 12 million people
worldwide.

The most common treatment-emergent adverse event associated with
olanzapine 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, akathisia, postural
hypotension, dry mouth, asthenia, dyspepsia, increased appetite, and
tremor.

A small number of patients in premarketing trials experienced
asymptomatic elevations of hepatic transaminase; none of these
patients developed jaundice. Periodic assessment of transaminases is
recommended in patients with significant hepatic disease.

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

Hyperglycemia and diabetes mellitus -- Hyperglycemia, in some cases
associated with ketoacidosis, coma, or death, has been reported in
patients treated with atypical antipsychotics including olanzapine.
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.

About Eli Lilly and Company

Lilly, a leading innovation-driven corporation, is developing a
growing portfolio of 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 www.lilly.com.