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Pharmacoeconomic evaluation in schizophrenia: clozapine in treatment-resistant schizophrenia and risperidone in chronic schizophrenia.

Cite as: Glennie JL. Pharmacoeconomic evaluations of clozapine in treatment-resistant schizophrenia and risperidone in chronic schizophrenia. Ottawa: Canadian Coordinating Office for Health Technology Assessment (CCOHTA); 1997.

Background
Schizophrenia is a prevalent psychiatric disorder with extremely high direct, indirect, and intangible costs to patients, their families, and society. Traditional approaches to therapy do not adequately treat all symptoms of schizophrenia, and fail in up to 30% of patients through lack of response or intolerable adverse events. Risperidone and clozapine are recently introduced therapeutic alternatives which offer lower rates of adverse effects and improved symptom control. Unit costs for these agents are higher than traditional therapies. This factor, coupled with the absence of long-term outcome information (risperidone) and the presence of potentially severe adverse effects (clozapine), makes it difficult to define the most appropriate role(s) for these medications.

To address these issues, a study commissioned by CCOHTA entitled "Pharmacoeconomic Evaluation of Risperidone and Clozapine in Chronic and Treatment-Resistant Schizophrenia" evaluated the use of these agents in schizophrenia. Specifically, the study's objectives were to carry out a comparative therapeutic and economic evaluation of: a) clozapine in treatment-resistant schizophrenic patients or those suffering from debilitating adverse effects from conventional phenothiazines; and of, b) risperidone as first line therapy for patients with schizophrenia, and in patients suffering adverse effects from phenothiazines.

Conclusions
  1. The cost-utility analysis demonstrated that clozapine was the dominant strategy compared to chlorpromazine or haloperidol in hospitalized patients with treatment-resistant schizophrenia with moderate symptoms. The estimated cost savings was approximately $39,000 per patient per year while producing 0.04 more quality-adjusted life years (QALYs) per year.

  2. In this situation, the use of clozapine may be associated with $389 million in annual cost savings in direct health care expenditures, mainly due to reduced hospitalization. The associated incremental increase in drug expenditure would be $63 million (approximately $6,300 per patient per year).

  3. The cost-utility analysis demonstrated that risperidone was the dominant strategy compared to haloperidol, haloperidol decanoate or fluphenazine decanoate in hospitalized patients with chronic schizophrenia with moderate symptoms. The estimated cost savings (versus haloperidol) was approximately $6,500 per patient per year while producing 0.04 more QALYs per year.

  4. In the above situation, the use of risperidone may be associated with $662 million in annual cost savings in direct health care expenditures (overall, approximately $9,500 savings per patient per year) mainly due to reduced hospitalization. The associated incremental increase in drug expenditure would be $113 million (approximately $1,600 per patient per year).

  5. The savings in direct health care expenditures for both of these medications were conditional upon the presence of adequate services to support the care of these patients in the community. These savings were based on a reduction in hospitalization, and no savings accrue if patients remain institutionalized due to inadequate community-based care.

  6. The clinical outcome, cost, and utility results of these analyses do not apply to the more general schizophrenic population, or those in the early stages of their disease. The role of clozapine and risperidone in these groups remains to be studied.

  7. The limitations of these analyses include: the absence of long-term outcome data, thus mandating a modeling approach; the absence of a Monte Carlo sensitivity analysis to evaluate the impact of concurrent changes in multiple parameters in the model; the absence of information regarding costs or savings accrued via avoiding tardive dyskinesia; the very small number of subjects available for utility assessment; and interprovincial analyses which focused only on drug price variation and did not take into account variation in the non-drug component (primarily hospitalization and community care costs).