Context Although olanzapine has been widely adopted as a treatment of choice
for schizophrenia, its long-term effectiveness and costs have not been evaluated
in a controlled trial in comparison with a standard antipsychotic drug.
Objective To evaluate the effectiveness and cost impact of olanzapine compared
with haloperidol in the treatment of schizophrenia.
Design and Setting Double-blind, randomized controlled trial with randomization conducted
between June 1998 and June 2000 at 17 US Department of Veterans Affairs medical
Participants Three hundred nine patients with a Diagnostic and
Statistical Manual of Mental Disorders, Fourth Edition diagnosis of
schizophrenia or schizoaffective disorder, serious symptoms, and serious dysfunction
for the previous 2 years. Fifty-nine percent fully completed and 36% partially
completed follow-up assessments.
Interventions Patients were randomly assigned to receive flexibly dosed olanzapine,
5 to 20 mg/d, with prophylactic benztropine, 1 to 4 mg/d (n = 159); or haloperidol,
5 to 20 mg/d (n = 150), for 12 months.
Main Outcome Measures Standardized measures of symptoms, quality of life, neurocognitive status,
and adverse effects of medication. Veterans Affairs administrative data and
interviews concerning non-VA service use were used to estimate costs from
the perspective of the VA health care system and society as a whole (ie, consumption
of all resources on behalf of these patients).
Results There were no significant differences between groups in study retention;
positive, negative, or total symptoms of schizophrenia; quality of life; or
extrapyramidal symptoms. Olanzapine was associated with reduced akathisia
in the intention-to-treat analysis (P<.001) and
with lower symptoms of tardive dyskinesia in a secondary analysis including
only observations during blinded treatment with study drug. Small but significant
advantages were also observed on measures of memory and motor function. Olanzapine
was also associated with more frequent reports of weight gain and significantly
greater VA costs, ranging from $3000 to $9000 annually. Differences in societal
costs were somewhat smaller and were not significant.
Conclusion Olanzapine does not demonstrate advantages compared with haloperidol
(in combination with prophylactic benztropine) in compliance, symptoms, extrapyramidal
symptoms, or overall quality of life, and its benefits in reducing akathisia
and improving cognition must be balanced with the problems of weight gain
and higher cost.