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

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 centers. 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 dollars to 9000 dollars 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.

Inpatient length of stay and atypical antipsychotic use among elderly patients with psychiatric disorders and Alzheimer's disease.

This study evaluated length of stay (LOS) associated with atypical antipsychotic monotherapy in inpatients with Alzheimer's disease. In addition to sociodemographic information, data were also obtained on severity of illness, medications, used, patient satisfaction, and hospitalization. Sociodemographics and severity of illness at admission were similar in groups taking olanzapine (N = 66), quetiapine (N = 41), and risperidone (N = 147). The mean LOS for risperidone was significantly shorter than that for quetiapine (12.3 vs. 16.4 days, respectively; P < .02), but the difference between risperidone and olanzapine did not reach statistical significance (12.3 vs. 14.9 days, respectively; P < .08). The savings associated with risperidone versus quetiapine therapy, based on an estimated daily hospital care cost of $492, was $2,017.20 per patient.

Olanzapine versus risperidone in the treatment of schizophrenia : a comparison of costs among Texas Medicaid recipients.

OBJECTIVE: To examine both schizophrenia-related costs and total (schizophrenia plus non-schizophrenia) healthcare costs among Texas Medicaid recipients who had been diagnosed with a schizophrenic disorder and had been initiated on olanzapine or risperidone. METHODS: Cost data for services and prescription use were retrieved for 2,885 patients with schizophrenia who were initiated on olanzapine or risperidone between 1 January 1997 and 31 August 1998. Each patient was followed for 1 year before and 1 year after initiation of therapy. Multivariate analysis was used to control for a wide range of factors (drug choice, patient demographics, pre-utilisation costs, region, health conditions, and treatment patterns) that may influence schizophrenia-related costs and total healthcare costs. Estimation was conducted via a two-stage instrumental variables model. RESULTS: The mean unadjusted total schizophrenia-related cost per patient per year during the observation period was 4,892 US dollars, and the total unadjusted healthcare cost per patient was 7,101 US dollars. Results revealed significant regional variation in schizophrenia-related and total healthcare costs. Significantly higher total healthcare costs were found for patients with other (nonpsychiatric) diagnoses, such as HIV and diabetes mellitus. Although, on average, patients taking olanzapine stayed on therapy longer than those taking risperidone (248.2 days vs 211.1 days; p < 0.0001), multivariate analysis revealed no significant difference in schizophrenia-related costs between patients who received olanzapine and risperidone (123 US dollars lower with olanzapine; p = 0.6439). However, patients who received olanzapine compared with risperidone had significantly lower total medical costs (693 US dollars lower with olanzapine; p = 0.0311). CONCLUSION: This naturalistic study used data from a Texas Medicaid population to examine the schizophrenia-related costs and total healthcare costs for patients who received olanzapine versus risperidone. Multivariate analysis revealed no significant differences in schizophrenia-related costs for patients receiving olanzapine compared with risperidone, although total medical costs were significantly lower for patients initiated on olanzapine.

Risperidone compared with olanzapine in a naturalistic clinical study: a cost analysis.

BACKGROUND: Risperidone and olanzapine are thought to have broadly similar clinical effects. This study was designed as a cost analysis study comparing costs and basic clinical outcomes of treatment with risperidone or olanzapine in a naturalistic setting. METHOD: The U.K. Risperidone Olanzapine Drug Outcomes Studies in Schizophrenia (RODOS-UK) program consisted of a retrospective review of medical notes and prescription charts for 501 patients with schizophrenia or schizoaffective disorder who had been admitted to the hospital for the treatment of psychosis. The main outcome measure was cost of inpatient drug treatment. Clinical outcomes (clinician-assessed and -documented effectiveness, time to discharge) were also evaluated. Data were collected and verified between June and September 2000. RESULTS: Clinical outcomes were similar for risperidone and olanzapine. Clinician-assessed effectiveness was similar for both treatments (78% risperidone, 74% olanzapine; p =.39), but mean time to documented onset of effectiveness was significantly shorter for those treated with risperidone versus olanzapine (17.6 vs. 22.4 days; p =.01). Risperidone-treated patients stayed a mean of 9 fewer days in the hospital compared with olanzapine-treated patients (49 vs. 58 days; p =.007). The possibility that these observed differences were a result of different baseline characteristics could not be entirely discounted. Mean +/- SD doses of risperidone and olanzapine were 5.5 +/- 2.4 mg/day and 14.1 +/- 4.7 mg/day, respectively. The mean daily cost of all inpatient drugs was significantly higher for olanzapine than for risperidone (pound 5.63 vs. pound 3.92; p <.0001). Mean total costs of all inpatient drugs were significantly higher for olanzapine than for risperidone (pound 164 vs. pound 96; p <.0001), which partly reflected the longer mean treatment duration for olanzapine compared with risperidone (44 vs. 37 days). Concomitant antipsychotic use was similar for both groups (66% risperidone, 67% olanzapine). The number of patients documented as experiencing adverse events was not different between groups (22% risperidone, 19% olanzapine; p =.32). CONCLUSION: Risperidone and olanzapine produced broadly comparable clinical outcome in this cohort of hospitalized patients, but the use of risperidone was associated with significantly lower drug treatment costs.

The European Schizophrenia Outpatient Health Outcomes Study: baseline findings across country and treatment.

OBJECTIVE: To describe the baseline findings and study population of the Schizophrenia Outpatient Health Outcomes (SOHO) Study. METHOD: The SOHO study is an ongoing, large, prospective, long-term observational study of schizophrenia treatment in 10 European countries. The study population consists of out-patients who initiate therapy or change to a new antipsychotic. RESULTS: A total of 1096 investigators enrolled 10 972 patients. Approximately 60% of patients were men and the mean age was 40 years. Patients treated with clozapine and more than one antipsychotic are more severely ill, patients receiving depot medications have a history of non-compliance, and patients receiving their first antipsychotic for schizophrenia are most likely to receive an atypical agent. CONCLUSION: The SOHO study population appears to represent European out-patients with schizophrenia in whom a treatment decision is required. Baseline findings reflect European clinical practice with respect to patients treated with individual antipsychotics.

Olanzapine vs risperidone in the management of schizophrenia: a randomized double-blind trial in Australia and New Zealand.

Improved drug therapy for schizophrenia may represent the best strategy for reducing the costs of schizophrenia and the recurrent chronic course of the disease. Olanzapine and risperidone are atypical antipsychotic agents developed to meet this need. We report a multicenter, double-blind, parallel, 30-week study designed to compare the efficacy, safety, and associated resource use for olanzapine and risperidone in Australia and New Zealand. The study sample consisted of 65 patients who met DSM-IV criteria for schizophrenia, schizoaffective disorder, or schizophreniform disorder. Olanzapine-treated patients showed a significantly greater reduction in Positive and Negative Syndrome Scale (PANSS) total, Brief Psychiatric Rating Scale (BPRS) total, and PANSS General Psychopathology scores at endpoint compared to the risperidone-treated patients. Response rates through 30 weeks showed a significantly greater proportion of olanzapine-treated patients had achieved a 20% or greater improvement in their PANSS total score compared to risperidone-treated patients. Olanzapine and risperidone were equivalent in their improvement of PANSS positive and negative scores and Clinical Global Impression-Severity of Illness scale (CGI-S) at endpoint. Using generic and disease-specific measures of quality of life, olanzapine-treated patients showed significant within-group improvement in most measures, and significant differences were observed in favor of olanzapine over risperidone in Quality of Life Scale (QLS) Intrapsychic Foundation and Medical Outcomes Study Short Form 36-item instrument (SF-36) Role Functioning Limitations-Emotional subscale scores. Despite the relatively small sample size, our study suggests that olanzapine has a superior risk:benefit profile compared to risperidone.

Cost evaluation of risperidone compared with olanzapine.

This study evaluated costs associated with risperidone and olanzapine treatment for schizophrenia. Data were collected from the Department of Veterans Affairs computerized database nine months before and nine months after patients began continuous treatment with risperidone (N=23) or olanzapine (N=47). Both agents were associated with significant reductions in psychiatric hospitalization costs. Median increases in antipsychotic costs were significantly higher for patients treated with olanzapine ($1,892) than for those treated with risperidone ($733). Mean dosages were 3.5 mg per day for the risperidone group and 18 mg per day for the olanzapine group. Although both treatments were associated with similar reductions in costs of psychiatric inpatient and outpatient care, it was significantly less expensive to prescribe risperidone than olanzapine.

The European Schizophrenia Outpatient Health Outcomes (SOHO) study: rationale, methods and recruitment.

OBJECTIVE: The objective of the European Schizophrenia Outpatient Health Outcomes (SOHO) study is to understand the comparative costs and outcomes of antipsychotic drug treatment, with specific focus on olanzapine. The study will also provide a large database for research into the treatment and outcome of schizophrenia. The role of observational studies in the assessment of the effectiveness of antipsychotic agents is reviewed, and the rationale, design and recruitment issues surrounding the SOHO study are presented. METHOD: SOHO is a 3-year, prospective, observational study of the health outcomes associated with antipsychotic treatment in Europe. RESULTS: Over 10 000 patients have been recruited from 10 countries. Baseline evaluation included measures of clinical status, social functioning, quality of life, service use and pharmacological treatment. Patients will be followed for 3 years. CONCLUSION: The SOHO study will complement randomized controlled trial findings on the treatment of schizophrenia and will address relevant clinical and policy research questions.

Economic evaluations of novel antipsychotic medications: a literature review.

OBJECTIVE: To evaluate the evidence that novel antipsychotic medications offer a cost advantage compared to traditional antipsychotic medications. METHODS: Literature for this review was identified through a computerized search of Medline, Healthstar and Psyc-INFO databases inclusive from January 1989 to January 2002. Articles included in the review were required to include cost evaluation and to be published in peer-reviewed journals. RESULTS: Twenty-two studies met inclusion criteria. All five studies that used experimental designs found that second-generation antipsychotic medications were associated with a cost advantage or were cost-neutral, and, in some cases, improved quality of life. Of the ten studies using a pre-post design, four found an increase in total costs, six reported a decrease in total costs, and four reported increased effectiveness with use of a second-generation antipsychotic. All seven of the simulation studies reported a cost advantage for novel antipsychotics for specific patient populations under certain conditions. CONCLUSIONS: The majority of studies found that novel antipsychotics are at least cost-neutral and may offer cost advantages compared to traditional agents. Some studies also reported greater improvement in effectiveness and quality of life when novel antipsychotics were compared to traditional antipsychotic medications. However, it is difficult to draw firm conclusions given the small sample sizes and limited study designs available in this literature.

Use of atypical antipsychotics in a Veterans Affairs hospital.

In a retrospective chart review, efficacy and drug costs were compared in 91 consecutive outpatients receiving risperidone (n=70) or olanzapine (n=21) at the Veterans Affairs Medical Center in Syracuse, NY. Between-group differences in background characteristics, diagnoses (schizophrenia in more than half of each group) and antipsychotic efficacy [Clinical Global Impressions (CGI) scale scores] were not significant. The mean doses were 3.6+/-2.4 mg/day of risperidone and 10.7+/-7.6 mg/day of olanzapine. The VA costs of these mean doses were S3.32/day for risperidone and $6.67/day for olanzapine. Mean duration of treatment was significantly longer for risperidone (21 months) than for olanzapine (13 months). Incidence of parkinsonian symptoms (14% of both risperidone and olanzapine patients) and tardive dyskinesia (3% of risperidone patients and 5% of olanzapine patients) was similar in the two groups. Akathisia tended to occur more often in patients receiving olanzapine than risperidone (14% versus 3%, P=.08). The results of this retrospective survey indicate that, in comparable VA populations of patients with psychotic and other disorders, risperidone and olanzapine are equally efficacious but olanzapine may be more likely to produce akathisia and is twice as expensive as risperidone.

Economic, clinical, and quality-of-life outcomes associated with olanzapine treatment in mania. Results from a randomized controlled trial.

INTRODUCTION: The objectives of this study were to determine the economic, clinical, and quality-of-life outcomes associated with olanzapine treatment in patients diagnosed with mania. METHODS: Patients with a diagnosis of bipolar I disorder with manic or mixed episodes were enrolled in a randomized controlled trial. The study design comprised a 3-week acute phase followed by a 49-week open label extension. In the open label extension, the use of lithium and fluoxetine was permitted for patients who experienced breakthrough symptoms. Clinical, economic, and quality-of-life outcomes of treatment were assessed. RESULTS: During the acute phase, olanzapine patients experienced a statistically significant greater mean improvement from baseline on the Y-MRS total score compared to the placebo patients. In the open label extension, patients experienced a statistically significant mean change of 11.8 units on the Y-MRS from the end of the acute phase. When compared to costs incurred in the previous 12 months of therapy, patients experienced savings of almost $900 per month during the 49 weeks of olanzapine therapy. These cost savings were largely driven by reductions in in-patient costs during the open label extension. Health-related quality of life improvements measured by the SF-36 were seen on several dimensions both in the 3-week acute phase as well as in the 49-week open label extension. CONCLUSION: From a clinical, economic, and quality-of-life outcomes standpoint, olanzapine had a significant impact in the treatment of mania, and could be considered a cost-effective treatment option for use in this population if these findings are extrapolated to non-clinical trial populations.

Clinical and economic outcomes associated with olanzapine for the treatment of psychotic symptoms in a county mental health population.

BACKGROUND: The comparatively high acquisition costs of the newer antipsychotic medications have caused the mental health community to look closely at their potential benefits. OBJECTIVE: The purpose of this study was to perform a naturalistic analysis of changes in mental health service utilization, economic costs, and clinical outcomes after the initiation of olanzapine therapy for psychotic symptoms in an indigent patient population from a large county-operated mental health care system. METHODS: This was a prospective, uncontrolled investigation using a mirror-image cohort design. All captured costs from patients who began olanzapine therapy between November 1, 1996, and April 30, 1998, were analyzed in an intent-to-treat fashion to compare resource utilization in the 12 months immediately before and after the intervention. Clinical function was assessed at baseline and 6 months using the Positive and Negative Syndrome Scale (PANSS). In a subgroup analysis, the baseline characteristics of patients who completed 12 months of olanzapine treatment were compared with those of patients who (1) changed medication or (2) changed pay or source or were lost to follow-up. RESULTS: One hundred eighty-nine patients were started on olanzapine treatment during the 18-month study entry phase. Patients were primarily male (63.5%) and had a mean age of 35.9 years. Most (66.3%) had a formal diagnosis of thought disorder. Fifty-six patients received olanzapine for 12 consecutive months, and 22 were switched to other psychotropic medications. Of the remaining 111 patients, 70 changed payors (ie, qualified for Medicaid), and 41 were lost to follow-up. In the subgroup analysis, patients who completed 12 months of treatment (ie, responders) had significantly lower mean PANSS total scores at baseline compared with those who changed payors or were lost to follow-up (P = 0.047), and were significantly more likely to have a formal diagnosis of thought disorder (P = 0.039). Responders demonstrated a significant reduction in PANSS total and negative subscale scores at 6-month follow-up (both measures, P < 0.001). In the intent-to-treat analysis of resource utilization in all patients with complete data sets (n = 78), hospitalization costs and crisis costs decreased significantly during the 12-month follow-up period (P = 0.003 and P = 0.009, respectively), and both outpatient and medication costs increased significantly (P = 0.035 and P < 0.001, respectively). Overall, the change in total annual resource utilization during the 12 months after initiation of olanzapine was not statistically significant (mean decrease per patient, $1,991; 95% CI, -$5,258 to $1,122). CONCLUSIONS: Initiation of olanzapine therapy was associated with favorable clinical outcomes in this population, particularly in patients with a formal diagnosis of thought disorder. Overall, there was a cost shift away from hospital and crisis costs toward medication and outpatient services costs. The decline in total resource utilization was not statistically significant, although it may be of practical importance.

A retrospective economic evaluation of olanzapine versus risperidone in the treatment of schizophrenia.

This retrospective study evaluates drug treatment patterns and economic outcomes of olanzapine in comparison with risperidone in the treatment of schizophrenia in usual practice. Results showed that patients taking olanzapine versus risperidone stayed on therapy longer (P < .0001) and were prescribed anti-Parkinsonian medications less frequently (P < .005). Compared with risperidone, olanzapine treatment resulted in lower direct mental health care costs ($1,827 less, P < .03) and lower direct total health care costs ($1,834 less, P < .05). The results of this study suggest that the initial selection of an antipsychotic for the treatment of schizophrenia is important: Olanzapine offset its acquisition cost by reducing medical service costs and demonstrated better drug treatment patterns than risperidone.

Cost-effectiveness of risperidone, olanzapine, and conventional antipsychotic medications.

To assess the cost and effectiveness of risperidone, olanzapine, and conventional antipsychotic medications under "usual practice" conditions in a large, public mental health system, 108 persons diagnosed with schizophrenia or schizoaffective disorder were randomly assigned to one of these three medication groups and followed prospectively over a 12-month period using standard instruments and procedures. Psychiatric medication costs increased more over time in both the olanzapine and risperidone groups than in the conventional medication group. Compliance with the prescribed medication was higher in the olanzapine group than in the conventional group. No differential effects by medication group were evident in this sample on the symptoms of schizophrenia, side effects, psychosocial functioning, time to discharge for index hospitalization, survival to initial rehospitalization, or client satisfaction with services. These results extend findings from previous efficacy and naturalistic studies in several ways but are limited chiefly by the small number of subjects who completed 6 to 12 months of the clinical trial, and the resulting power to detect differences in the statistical analyses.

National Institute of Mental Health Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE): Alzheimer disease trial methodology.

The authors describe the development of the Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE) protocol for Alzheimer disease (AD), a trial developed in collaboration with the National Institute of Mental Health (NIMH), assessing the effectiveness of atypical antipsychotics for psychosis and agitation occurring in AD outpatients. They provide an overview of the methodology utilized in the trial as well as the clinical-outcomes and effectiveness measures that were implemented.

The effect of institutional fiscal stress on the use of atypical antipsychotic medications in the treatment of schizophrenia.

This paper examines the effects of medical center budget stress on the use of expensive atypical antipsychotic medications for the treatment of schizophrenia in the Department of Veterans Affairs (VA). VA prescription drug records were collected for patients diagnosed with schizophrenia. Generalized estimation equations were used to identify patient and facility characteristics (especially fiscal stress) that are associated with the use of atypical antipsychotics. Of the 34,925 patients in the final sample, over half received an atypical antipsychotic, usually either olanzapine or risperidone. Unexpectedly, increased fiscal stress was associated with increased likelihood of receiving atypical antipsychotics. Among patients who receive atypicals, however, fiscal stress was associated with reduced likelihood of receiving the more expensive atypicals (clozapine and olanzapine) but positively associated with receiving the least expensive atypical (risperidone). Institutional fiscal pressure does not seem to reduce the broad availability of these medications overall but does affect which drug is prescribed.