Clozapine, diabetes mellitus, weight gain, and lipid abnormalities: A five-year naturalistic study.

OBJECTIVE: The goal of this 5-year naturalistic study of patients treated with clozapine was to examine the incidence of treatment-emergent diabetes mellitus in relation to other factors, including weight gain, lipid abnormalities, age, clozapine dose, and treatment with valproate. METHOD: Data on age, gender, race, diagnosis, family history of diabetes, and age at clozapine initiation were collected from medical records of 82 outpatients with schizophrenia or schizoaffective disorder. Clozapine dose, data on use of valproate, and laboratory test results were recorded at 6-month intervals. RESULTS: The mean age at the time of clozapine initiation of the 82 patients was 36.4 years; 26.8% of the patients were women, and 91.5% were Caucasian. The mean baseline weight was 175.5 lb, and the mean body mass index was 26.9 kg/m(2). Thirty patients (36.6%) were diagnosed with diabetes during the 5-year follow-up. Weight gain, use of valproate, and total daily dose of clozapine were not significant risk factors for developing diabetes mellitus. Patients experienced significant weight gain that continued until approximately month 46 from initiation of clozapine. There was a nonsignificant increase in total serum cholesterol and a significant increase in serum triglycerides level. CONCLUSIONS: The results support the hypotheses that patients treated with clozapine experience significant weight gain and lipid abnormalities and appear to be at increased risk for developing diabetes.

Switching from clozapine to olanzapine in treatment-refractory schizophrenia: safety, clinical efficacy, and predictors of response.

BACKGROUND: In our experience, many of our schizophrenic patients treated with clozapine request the newer atypical antipsychotic agents in order to eliminate the weekly blood monitoring. However, there are few guidelines available to clinicians interested in switching patients successfully treated with clozapine to olanzapine. METHOD: The goal of this study was to collect preliminary data on the safety, clinical effectiveness, and predictors of response of switching clozapine patients to olanzapine. In an open trial, 19 patients receiving clozapine were switched to olanzapine. RESULTS: Eight (42%) of 19 patients were considered responders. Seven patients decompensated seriously enough to require hospitalization. All 7 of these patients were restabilized on clozapine treatment in the hospital, and olanzapine was discontinued. In an additional 4 patients, clinical status worsened, and clozapine doses were titrated upwards and olanzapine was slowly discontinued. Overall, mean total Brief Psychiatric Rating Scale (BPRS) scores increased significantly from baseline to final assessment (p = .02). Responders had been treated for a significantly shorter period of time with clozapine prior to the switch compared to nonresponders (p = .04) and were receiving a lower dose of clozapine (p = .05). The final olanzapine dose did not differ between responders and nonresponders. All responders have remained on olanzapine treatment and are stable. CONCLUSION: In this open trial, the crossover from clozapine to olanzapine was generally well tolerated and resulted in a successful transition for 8 of the 19 patients. However, mean scores on the total BPRS and negative symptom and depressive symptom subscales significantly increased. Caution must be taken in determining which patients may benefit from the switch to olanzapine because of the risk of decompensation and hospitalization. Because this was an open trial, these findings require replication in a controlled trial.