Cost Evaluation of Risperidone Compared With Olanzapine

Risperidone and olanzapine, the most frequently prescribed antipsychotic medications in the United States, account for 31.1 percent and 25.2 percent, respectively, of all new antipsychotic prescriptions (1). These agents are more expensive than conventional antipsychotics, which restricts their use by some health care agencies. However, the superior efficacy of risperidone and olanzapine may be a factor in the results of studies that indicate cost savings or cost neutrality associated with these agents compared with conventional antipsychotics (2,3).

Clear differences in the efficacy or tolerability of risperidone compared with olanzapine have yet to be demonstrated. For example, in one study olanzapine was associated with fewer treatment-emergent adverse events than risperidone (4). However, Conley and Mahmoud (5) found that adverse events were more commonly associated with olanzapine treatment during a head-to-head trial when these agents were used at dosages consistent with clinical practice in the United States. It is possible that comparing the costs of treatment will better indicate the relative benefits of the two agents.

Few studies have compared costs of the newer antipsychotic medications in a head-to-head manner. In one retrospective study, the average daily acquisition costs varied from $2.91 to $4.31 for risperidone and from $4.22 to $6.29 for olanzapine. No statistical comparisons of these costs were provided, nor were correlations drawn between use of these medications and other health service use or clinical outcomes (6). Another retrospective study showed that daily drug acquisition costs were significantly lower for risperidone ($4.69) than olanzapine ($11.52) (p<.001). Clinical outcome (improvement in at least one target symptom) was also superior among patients who were treated with risperidone (p<.01) (7).

In the retrospective study reported here, we compared patients who received at least nine months of treatment with either risperidone or olanzapine.

Methods

We identified all patients in the database of the Little Rock Department of Veterans Affairs (VA) Medical Center who had ICD-9 diagnoses of schizophrenia or schizoaffective disorder and who began treatment with risperidone or olanzapine after November 4, 1996—the date olanzapine was first prescribed at this site. Patients who received treatment with risperidone or olanzapine for nine consecutive months and received care at the medical center nine months before treatment were included in the study. Approval for the study was obtained from the institutional review board of the University of Texas Southwestern Medical Center at Dallas. The institutional review board deemed that it was not necessary to obtain individual informed consent from the patients.

Costs of antipsychotic acquisition and psychiatric inpatient and outpatient care were collected from the medical center's database in May 1998. Cost-outcomes data were collected for nine months before and nine months after each patient began nine months of treatment with risperidone or olanzapine—referred to here as the pre-index period and the post-index period, respectively.

Direct psychiatric hospitalization costs for each patient were calculated by multiplying the number of service days by the per-day cost of each inpatient unit as determined by the Little Rock VA medical center's quarterly cost and distribution report from the final quarter of 1997. The final cost equaled the sum of hospital care on the three inpatient psychiatric units. Outpatient psychiatric care costs were estimated by multiplying the number of three different outpatient procedures—medication management, individual psychotherapy, and group psychotherapy—by the cost per procedure on the basis of a 1997 VA national cost report (8).

Demographic data were compared by using Student's t test or the chi square test for continuous and noncontinuous variables, respectively. Wilcoxon's rank sum test was used to evaluate pre-post (within-group) comparisons, and the Mann-Whitney U test was used to assess between-group comparisons. Two-tailed statistical tests at an alpha level of .05 were performed for all variables. Patients for whom psychiatric care costs—total psychiatric inpatient, outpatient, and antipsychotic costs—were greater than $5,000 during the pre-index period were considered to be high utilizers.

Results

Among the 23 patients in the risperidone group, eight (35 percent) were high utilizers, compared with 21 (45 percent) of the 47 patients in the olanzapine group. Patients in the risperidone group were significantly older than those in the olanzapine group (p=.001). However, a comparison of high utilizers revealed no between-group differences in age.

Wilcoxon's rank sum test showed significant reductions between the pre- and post-index periods in psychiatric hospitalization costs for both risperidone (p=.012) and olanzapine (p=.009). A comparison of change in psychiatric hospitalization costs revealed no significant difference between the two treatment groups. Both groups demonstrated minimal and similar increases in psychiatric outpatient care costs, with a median group increase of $192.

As can be seen from Table 1, the median change in antipsychotic costs between the pre- and post-index periods was significantly higher for patients in the olanzapine group ($1,892) than for those in the risperidone group ($733). Among high utilizers, the median change in antipsychotic costs remained significantly higher for patients treated with olanzapine than for those treated with risperidone (p=.009). The mean change in antipsychotic costs was 58 percent lower for the risperidone group ($760 compared with $1,831).

Mean dosages after the post-index period were 3.5 mg per day for risperidone and 18 mg per day for olanzapine. The median post-index cost for the risperidone group was $744, an amount significantly less than the median of $2,275 for olanzapine (p<.001). The mean cost of nine months of treatment with risperidone was about one-third that of olanzapine ($814 compared with $2,406).

Discussion and conclusions

Risperidone and olanzapine were both associated with significant decreases in psychiatric hospitalization costs—the largest contributor to the costs of care in this patient population (2,3). Between the pre-index period and the post-index period, antipsychotic costs increased by a median of $733 for patients in the risperidone group and $1,892 for those in the olanzapine group, a significant difference (p<.001). No between-group differences were found in changes in costs of psychiatric inpatient or outpatient care.

The head-to-head design of this study provided a cost evaluation of the new antipsychotic agents by using psychiatric hospitalization and use of psychiatric outpatient services as indicators of patient responsiveness and stability. The relatively long duration of patient follow-up (nine months) and the use of direct cost data rather than estimates were also major strengths of the study.

Limitations of the study include its retrospective design and limited sample size. Another potential limitation was the nonsignificant trend toward higher costs of psychiatric hospitalization in the pre-index period in the olanzapine group. Although not significant, this finding could indicate greater severity of illness among patients who are treated with olanzapine. This trend could have introduced a bias that underestimated the ability of olanzapine to reduce costs and could indicate a tendency toward greater treatment resistance among these patients.

In addition, 16 of the 47 patients in the olanzapine group received risperidone immediately before starting treatment with olanzapine, whereas only one patient in the risperidone group had previously received olanzapine. Thus it is possible that a subgroup of patients in the olanzapine group did not respond to risperidone. However, when patients who began olanzapine treatment immediately after discontinuing risperidone were excluded from the analysis, there were still no between-group differences in psychiatric hospitalization costs or psychiatric outpatient costs.

In the same analysis, the increase in antipsychotic costs was significantly higher for the olanzapine group (p=.001). A comparison of high utilizers similarly showed no significant differences in changes in psychiatric inpatient or outpatient costs but higher medication costs for the olanzapine group than for the risperidone group (p=.009).

Conversely, because risperidone treatment was associated with very low posttreatment psychiatric hospitalization costs (mean cost of $918), additional potential cost-reducing effects of risperidone may have been limited by a "ceiling effect"—that is, costs of psychiatric hospitalization could not be reduced below zero.

Additional studies are needed to detect meaningful differences in the overall cost-effectiveness of newer antipsychotic agents, including measures of total psychiatric care costs, general medical costs, and costs outside the care system.

Acknowledgment

This study was supported in part by Janssen Research Foundation. The authors thank James Cross and Diane McConnell, M.S.W., for their assistance in data acquisition and Amy Waerhouse for her assistance in manuscript preparation.

Dr. Byerly, Dr. Weber, and Dr. Casey are affiliated with the department of psychiatry of the University of Texas Southwestern Medical Center at Dallas, 5959 Harry Hines Boulevard, Professional Office Building 1, Suite 600, Dallas, Texas 75390-9101 (e-mail, [email protected]). Ms. Brooks is with the department of psychiatry of the University of Arkansas for Medical Sciences in Little Rock. Ms. Elliot and Dr. Hawkins are with the Department of Veterans Affairs Medical Center in Little Rock. A version of this article was presented at the annual meeting of the American Psychiatric Association held May 15 to 20, 1999, in Washington, D.C.

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