Estimating the consequences of anti-psychotic induced weight gain on health and mortality rate.

Many anti-psychotic medications produce marked weight gain. In this study, we estimate the expected impact of degrees of antipsychotic-induced weight gain on selected mortality rate and incidence rates of impaired glucose tolerance (IGT) and hypertension (HTN) among US adults. Using raw data from 5209 respondents from the Framingham Heart Study's public use data set and national statistics on population demographics, we estimated the expected effect of weight gain on number of deaths and incident cases of IGT and HTN for a 10-year period commencing in 1999. Results indicated that the estimated deleterious effects of weight gain were greater for people with higher BMIs at baseline, for greater degrees of weight gain, for men than women, and for older than younger persons. Because there is a 'U-shaped' relation between BMI and mortality rate, small to moderate weight gains among people with baseline BMIs less than 23 were predicted to decrease mortality rates, whereas weight gains among people with baseline BMIs above that level were expected to increase mortality rates. However, the relations of IGT and HTN with BMI are monotonically increasing. Thus, the anticipated effect of weight gain on IGT and HTN is deleterious regardless of baseline BMI. Because it is unclear whether the beneficial effects of the atypical agents on, for example, reducing suicide mortality, outweigh the putative increase in mortality due to weight gain, we estimate the beneficial effects due to decreased death from suicide with the potential deleterious effects due to a 10-kg weight gain. We found that 492 suicide deaths per 100,000 schizophrenic patients would be prevented over 10 years with the use of clozapine compared to 416 additional deaths due to antipsychotic induced weight gain. Although this estimate is rather crude and should be seen only as offering a sense of the likely situation, results suggest that the lives saved via clozapine may essentially be offset by the deaths due to weight gain. As we discuss, it is not possible to provide definitive estimates of the effect of antipsychotic-induced weight gain on health and mortality, but our findings suggest that the magnitude of weight gains induced by many antipsychotic agents is likely to have important deleterious effects on mortality and health.

Ziprasidone 80 mg/day and 160 mg/day in the acute exacerbation of schizophrenia and schizoaffective disorder: a 6-week placebo-controlled trial. Ziprasidone Study Group.

In this double-blind study, patients with an acute exacerbation of schizophrenia or schizoaffective disorder were randomized to receive either ziprasidone 80 mg/day (n = 106) or 160 mg/day (n = 104) or placebo (n = 92), for 6 weeks. Both doses of ziprasidone were statistically significantly more effective than placebo in improving the PANSS total, BPRS total, BPRS core items, CGI-S, and PANSS negative subscale scores (p < .05). Ziprasidone 160 mg/day significantly improved depressive symptoms in patients with clinically significant depression at baseline (MADRS > or = 14, over-all mean 23.5) (p < .05) as compared with placebo. The percentage of patients experiencing adverse events was similar in each treatment group, and resultant discontinuation was rare. The most frequent adverse events associated with ziprasidone were generally mild dyspepsia, nausea, dizziness, and transient somnolence. Ziprasidone was shown to have a very low liability for inducing movement disorders and weight gain. The results indicate that ziprasidone is effective and well tolerated in the treatment of the positive, negative, and depressive symptoms of an acute exacerbation of schizophrenia or schizoaffective disorder.

Multistage test procedure for testing Blackwelder's hypothesis of equivalence.

Suppose, in a clinical trial, the interest is to show that the effectiveness of an experimental therapy is no worse than that of the standard therapy by more than a specified amount, say delta units. Blackwelder (1) discussed this problem in clinical trials where the outcome of interest is dichotomous. The group sequential procedures developed by DeMets and Ware (2) are valid to test Blackwelder's hypothesis for the case delta = 0. In this paper, the asymmetric procedure of DeMets and Ware is modified to handle the case delta > 0. A two-stage procedure is considered in a drug interaction study that focuses on a specific side effect as the event of interest.