Changes in Antipsychotic Changes in Antipsychotic Pharmacotherapy and Healthcare Costs Pharmacotherapy and Healthcare Costs Following a New Diagnosis of Diabetes Following a New Diagnosis of Diabetes

among Patients with Schizophreniaamong Patients with Schizophrenia

Douglas L. Leslie, PhDDouglas L. Leslie, PhDRobert Rosenheck, MDRobert Rosenheck, MD

New England Mental Illness Research, Education and New England Mental Illness Research, Education and Clinical Center (MIRECC);Clinical Center (MIRECC);

VA Northeast Program Evaluation Center (NEPEC);VA Northeast Program Evaluation Center (NEPEC);Yale Medical SchoolYale Medical School

BackgroundBackground

First-generation antipsychotics were introduced First-generation antipsychotics were introduced in the 1950’sin the 1950’s

Second-generation antipsychoticsSecond-generation antipsychotics– clozapine, olanzapine, risperidone, quetiapineclozapine, olanzapine, risperidone, quetiapine– At least as effective as first-generation drugsAt least as effective as first-generation drugs– Have fewer side effectsHave fewer side effects– Associated with weight gain and diabetesAssociated with weight gain and diabetes

FDA warningFDA warning

ObjectivesObjectives

To determine risk of To determine risk of new-onsetnew-onset diabetes diabetes associated with antipsychotic medications.associated with antipsychotic medications.

To identify the costs associated with To identify the costs associated with treatment of new-onset diabetes.treatment of new-onset diabetes.

To determine whether patients switch To determine whether patients switch antipsychotic medications after diagnosis antipsychotic medications after diagnosis of diabetes.of diabetes.

SampleSample

Patients with schizophrenia treated in the VA Patients with schizophrenia treated in the VA Healthcare System.Healthcare System.

No pre-existing diabetes.No pre-existing diabetes.

““Stable” on an antipsychotic medication.Stable” on an antipsychotic medication.

Followed for up to 2 years between June 1999 Followed for up to 2 years between June 1999 and September 2001.and September 2001.

56,849 patients included in the study.56,849 patients included in the study.

MethodsMethodsPatients with a new diagnosis of diabetes Patients with a new diagnosis of diabetes were identified.were identified.

Cox proportional hazards model.Cox proportional hazards model.

A matched control group of patients who did A matched control group of patients who did not develop diabetes was identified.not develop diabetes was identified.

Medication changes and costs were Medication changes and costs were compared.compared.

Stable period (3 months)

Diabetes onset date

Diabetes patient

Study timelineStudy timeline

D

Stable period (3 months)

Pseudo diabetes onset date

Matched non-diabetes patient

D

June 1999 September 2001

ResultsResults

Patients were followed for an average of Patients were followed for an average of 15.7 months15.7 months

4,132 patients had a new diagnosis of 4,132 patients had a new diagnosis of diabetes – annual incidence rate of 4.36%diabetes – annual incidence rate of 4.36%

Unadjusted diabetes risk was highest for Unadjusted diabetes risk was highest for clozapine and olanzapineclozapine and olanzapine

Total healthcare costs were $3,104 higher Total healthcare costs were $3,104 higher for patients with diabetesfor patients with diabetes

Fitted survival functions from the Cox proportional hazards model predicting time to diabetes onset

0.88

0.90

0.92

0.94

0.96

0.98

1.00

0 5 10 15 20 25

Su

rviv

al

First-generation: refrisperidone: HR=1.01olanzapine: HR=1.15*quetiapine: HR=1.20clozapine: HR=1.57*

Month

Percentage of patients who switch/discontinue Percentage of patients who switch/discontinue antipsychotic medication after diabetes onsetantipsychotic medication after diabetes onset

Last medication Last medication before “diabetes date”before “diabetes date”

No No

diabetesdiabetes

WithWith

diabetesdiabetes pp

clozapineclozapine 9.8%9.8% 4.6%4.6% 0.0920.092

olanzapineolanzapine 25.2%25.2% 23.1%23.1% 0.1790.179

quetiapinequetiapine 40.1%40.1% 31.9%31.9% 0.0530.053

risperidonerisperidone 28.2%28.2% 24.2%24.2% 0.0230.023

conventionalconventional 24.3%24.3% 22.0%22.0% 0.0970.097

Diabetes risk and costs attributable Diabetes risk and costs attributable to second-generation drugsto second-generation drugs

MedicationMedication

AttributableAttributable

riskriskAttributable Attributable

cost per day*cost per day*

clozapineclozapine 2.03%2.03% $0.134$0.134

olanzapineolanzapine 0.63%0.63% $0.042$0.042

quetiapinequetiapine 0.80%0.80% $0.053$0.053

risperidonerisperidone 0.05%0.05% $0.003$0.003

* Based on average cost of $198/month per case of diabetes

Average cost Average cost per day of per day of

therapytherapy

$8.34$8.34

$6.86$6.86

$3.72$3.72

$3.65$3.65

ConclusionsConclusionsVery high rate of diabetes onset in this Very high rate of diabetes onset in this population (4-5% per year)population (4-5% per year)

Results do not support a “class effect”Results do not support a “class effect”

Onset of diabetes does not affect Onset of diabetes does not affect antipsychotic pharmacotherapyantipsychotic pharmacotherapy

Diabetes risk and treatment costs Diabetes risk and treatment costs attributable to second-generation drugs attributable to second-generation drugs are smallare small