Impact of clozapine prescription on inpatient resource utilization.

Although clozapine has been demonstrated to be clinically superior to typical neuroleptics in refractory schizophrenia, it is also more expensive. It had been hoped that the increased costs associated with its use would be offset by decreases in the utilization of other expensive resources, especially inpatient care. All patients who had clozapine initiated during an inpatient hospitalization within the VA for schizophrenia over a 4-year period (N = 1415) were matched with a comparison group (N = 2,830) on key service utilization variables and other possible confounding demographic and clinical variables using propensity scoring-an accepted statistical method, although still relatively little used in psychiatry. By using centralized VA databases, subsequent inpatient resource utilization for the 3 years after index discharge was examined. Veterans exposed to clozapine while inpatients recorded 33 (36%) more inpatient days in the subsequent 3 years after discharge than the comparison group (124 +/- 190 days vs. 91 +/- 181 days, p = .0002). When all patients exposed to clozapine were divided according to whether they had received 1 year of clozapine treatment after discharge, those that received less than 1 year's treatment recorded significantly more inpatient days than either those maintained on clozapine or controls. These results suggest that in actual practice clozapine treatment may cost substantially more than treatment with conventional neuroleptics.

An assessment of clinical practice of clozapine therapy for veterans.

Clozapine therapy for 2,996 patients with treatment-refractory schizophrenia was examined over a five-year period in the Veterans Affairs health care system. Patients were assessed with the Brief Psychiatric Rating Scale (BPRS) and the Abnormal Involuntary Movement Scale (AIMS). BPRS scores, which were available for 522 patients, indicated a significant improvement, as did AIMS scores, which were available for 252 patients. Compared with individuals who showed a modest improvement, those with a more robust response to clozapine had higher initial BPRS scores and were three times more likely to have been suicidal in the month before starting clozapine therapy.

Clozapine therapy for older veterans.

OBJECTIVE: The effectiveness of clozapine treatment in a treatment-refractory sample of older adult veterans with primary psychosis was examined. METHODS: Data were collected over a five-year period for patients age 55 and older who were given clozapine because of a history of treatment-refractory or treatment-intolerant psychosis. At initiation of clozapine therapy, baseline demographic, clinical, and psychopathology data were collected. At baseline and quarterly, patients' psychopathology was rated with the Brief Psychiatric Rating Scale (BPRS), and involuntary movements were rated with the Abnormal Involuntary Movement Scale (AIMS). RESULTS: The 329 patients age 55 or older who received clozapine during the study period represented 10 percent of all patients on clozapine therapy in the VA system. Of the 312 patients for whom demographic information was available, 294 were men and 18 were women. Overall, patients improved on clozapine therapy, although wide variation in drug response was observed. Complete BPRS and AIMS data were available for 97 patients. The 55- to 64-year-old group had a mean improvement in total BPRS score of 19.8 percent, with 42.6 percent showing more than a 20 percent improvement; those age 65 and older had a mean improvement of 5.7 percent, with 17.2 percent showing an improvement greater than 20 percent. The 97 patients with complete AIMS data showed a mean improvement of 16.6 percent in total score. CONCLUSIONS: Clozapine is an important therapeutic agent for older adults with treatment-refractory psychosis. Patients between the ages of 55 and 64 may have a better response than those age 65 and older.

Pattern Formation in the Arabidopsis Embryo Revealed by Position-Specific Lipid Transfer Protein Gene Expression.

During Arabidopsis embryogenesis, the zygote divides asymmetrically in the future apical-basal axis; however, a radial axis is initiated only within the eight-celled embryo. Mutations in the GNOM, KNOLLE, and KEULE genes affect these processes: gnom zygotes tend to divide symmetrically; knolle embryos lack oriented cell divisions that initiate protoderm formation; and in keule embryos, an outer cell layer is present that consists of abnormally enlarged cells from early development. Pattern formation along the two axes is reflected by the position-specific expression of the Arabidopsis lipid transfer protein (AtLTP1) gene. In wild-type embryos, the AtLTP1 gene is expressed in the protoderm and initially in all protodermal cells; later, AtLTP1 expression is confined to the cotyledons and the upper end of the hypocotyl. Analysis of AtLTP1 expression in gnom, knolle, and keule embryos showed that gnom embryos also can have no or reversed apical-basal polarity, whereas radial polarity is unaffected. knolle embryos initially lack but eventually form a radial pattern, and keule embryos are affected in protoderm cell morphology rather than in the establishment of the radial pattern.

Risk factors for clozapine discontinuation among 805 patients in the VA hospital system.

The goal of this study was to determine if demographic or clinical factors collected at baseline on patients treated with clozapine would increase the risk of having clozapine discontinued for (a) lack of response, (b) side effects, (c) noncompliance, (d) concomitant illness, or (e) death. The subjects were 805 patients treated with clozapine at 96 Department of Veterans Affairs Hospital System facilities. Multiple logistic regression was used to determine if any of the baseline variables predisposed patients to discontinuation from treatment. Factors which were studied include age, race, history of inadequate response to traditional neuroleptics, history of substance abuse, and DSM-III-R Axis I diagnosis. Of the 805 patients started on clozapine 167 (20.7%) were discontinued from treatment. The only significant variable in the logistic regression model was race. This study finds that African American patients are more likely to have clozapine discontinued than non-African American patients, and there is a trend for prior history of inadequate response to traditional neuroleptics to predict clozapine discontinuation. We found no effect of substance abuse or dependence, diagnosis, or age on outcome in the overall patient group. In a post hoc analysis the African American patients had a significantly lower baseline white blood count than the non-African American patients, which could have explained the difference in clozapine discontinuation. The findings of this study support further investigation into the causes of ethnic differences in treatment outcome with clozapine.