Effectiveness and cost of olanzapine and haloperidol in the treatment of schizophrenia: a randomized controlled trial.
BACKGROUND
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.


METHODS
Double-blind, randomized controlled trial with randomization conducted between June 1998 and June 2000 at 17 US Department of Veterans Affairs medical centers.


METHODS
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.


METHODS
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.


METHODS
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 dollars to 9000 dollars annually. Differences in societal costs were somewhat smaller and were not significant.


CONCLUSIONS
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.
Rosenheck
Robert
R
Department of Veterans Affairs Medical Center, West Haven, Conn., USA. Robert.Rosenheck@yale.edu
Perlick
Deborah
D
Bingham
Stephen
S
Liu-Mares
Wen
W
Collins
Joseph
J
Warren
Stuart
S
Leslie
Douglas
D
Allan
Edward
E
Campbell
E Cabrina
EC
Caroff
Stanley
S
Corwin
June
J
Davis
Lori
L
Douyon
Richard
R
Dunn
Lawrence
L
Evans
Denise
D
Frecska
Ede
E
Grabowski
John
J
Graeber
David
D
Herz
Lawrence
L
Kwon
Kong
K
Lawson
William
W
Mena
Felicitas
F
Sheikh
Javaid
J
Smelson
David
D
Smith-Gamble
Valerie
V
D000328:Adult; D017109:Akathisia, Drug-Induced; D014150:Antipsychotic Agents / Q000009:adverse effects / Q000191:economics* / Q000627:therapeutic use*; D001569:Benzodiazepines; D001590:Benztropine / Q000627:therapeutic use; D004311:Double-Blind Method; D005260:Female; D006220:Haloperidol / Q000009:adverse effects / Q000191:economics* / Q000627:therapeutic use*; D017048:Health Care Costs; D006296:Health Services / Q000706:statistics & numerical data; D006801:Humans; D008297:Male; D008875:Middle Aged; D018727:Muscarinic Antagonists / Q000627:therapeutic use; D009483:Neuropsychological Tests; D000077152:Olanzapine; D010890:Pirenzepine / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000191:economics* / Q000627:therapeutic use*; D011788:Quality of Life; D012559:Schizophrenia / Q000188:drug therapy* / Q000191:economics*; D016896:Treatment Outcome; D014481:United States
D014150:Antipsychotic Agents; D018727:Muscarinic Antagonists; D001569:Benzodiazepines; D001590:Benztropine; D010890:Pirenzepine; D006220:Haloperidol; D000077152:Olanzapine