Modelling the impact of compliance on the costs and effects of long-acting risperidone in Canada.

Schizophrenia is a chronic, relapsing disease that requires more healthcare resources to manage than any other single psychiatric illness. The main cost of treatment is hospitalization as a result of the exacerbation of symptoms often caused by poor compliance. Although the costs of hospitalization and relapse have been well documented, the differential effects of various medications on healthcare expenditure are still being determined. The aim of the present study was to estimate the cost effectiveness of long-acting risperidone in the treatment of high-risk, non-compliant patients with schizophrenia over a 5-year period in Canada. A discrete event model was developed comparing three scenarios, each with a different starting treatment: haloperidol depot, long-acting risperidone or oral risperidone. Second and third-line treatment options were olanzapine and clozapine, respectively, for all three scenarios. On the basis of 3000 simulated patient characteristics, the model generated individual patient histories. Outcomes included the number and duration of psychotic episodes, the cumulative Positive and Negative Syndrome Scale (PANSS) score and direct medical costs. The time horizon of the model was 5 years and a 5% discount rate was used for costs and effects. The perspective of the model was that of the Canadian healthcare system. After 5 years, treatment with long-acting risperidone saved Canada dollars 6908 and Canada dollars 13,130 (discounted) and avoided 0.28 and 0.54 relapses per patient, compared with haloperidol depot and oral risperidone, respectively. In this model, initiating treatment of high-risk, non-compliant patients with schizophrenia with long-acting risperidone was the dominant strategy. With long-acting risperidone, direct costs were lower and clinical effectiveness was greater, compared with haloperidol depot or oral risperidone, during years 4 and 5.

Investigation of Turner syndrome in schizophrenia.

Both Turner syndrome and schizophrenia are relatively infrequent conditions. Consequently, individuals having both illnesses are rare. Previous reviews of sex chromosome abnormalities in schizophrenia have focused primarily on the presence of supernumerary X-chromosomes. After identifying two female patients with schizophrenia and Turner syndrome, we reevaluated the available literature that survey female schizophrenics for the presence of chromosomal abnormalities. Eleven patients with Turner syndrome were identified among 6,483 females with schizophrenia in non-case-report studies. These survey results indicate that Turner syndrome occurs approximately three-fold more frequently in schizophrenic females than in the general female population (P < 0.02). Including 6 other case reports and our 2 cases, a total of 19 females with both schizophrenia and Turner syndrome were reported. Interestingly, whereas most Turner syndrome patients have the 45,X karyotype, the majority (18/19) of women with both illnesses have a mosaic karyotype (P < 0.0002). Given the potential role of genes on the X-chromosome in the pathogenesis of schizophrenia, the study of unique populations with abnormalities in this chromosome, such as women with Turner syndrome, may offer clues into this illness.

Drug metabolism and atypical antipsychotics.

The introduction of the atypical antipsychotics clozapine, risperidone, olanzapine, quetiapine and sertindole for the treatment of schizophrenia has coincided with an increased awareness of the potential of drug-drug interactions, particularly involving the cytochrome P450 (CYP) enzymes. The current literature describing the pharmacokinetics of the metabolism of these agents, including their potential to influence the metabolism of other medications, is reviewed. Clozapine appears to be metabolized primarily by CYP1A2 and CYP3A4, with additional contributions by CYP2C19 and CYP2D6. In addition, clozapine may inhibit the activity of CYP2C9 and CYP2C19, and induce CYP1A, CYP2B and CYP3A. Risperidone is metabolized by CYP2D6, and possibly CYP3A4. In vitro data indicate that olanzapine is metabolized by CYP1A2 and CYP2D6. Quetiapine is metabolised by CYP3A4 and sertindole by CYP2D6. There is, however, a general paucity of in vivo data regarding the metabolism of the atypical antipsychotics, indicating a need for further research in this area.