The potency of eight standard anticonvulsants was tested in dose-response studies on kindled rats. Animals with either amygdala- or cortical-generalized seizures were used, and the effects of drugs were assessed on: (1) amygdala focal activity; (2) cortical focal activity; and (3) the generalized convulsion triggered from either focus. Ethosuximide, which is used against absence attacks, was not effective at subtoxic levels against any type of kindled seizure. The seven other drugs, all of which are effective against tonic-clonic seizures, were found to be: (a) most potent against generalized convulsive seizures; (b) slightly less potent against cortical focal activity; and (c) only partially effective against amygdala focal activity even at high (toxic) doses. The effect of these drugs on kindled seizures closely parallels their known clinical effects against (respectively) tonic-clonic, simple partial, and complex partial attacks. It is concluded that the kindling preparation could provide new pharmacological models for several different types of clinical seizure. Its most important use, however, is likely to be as a model for complex partial seizures, since there is at present no satisfactory pharmacological model for these common and drug-resistant attacks.
The current study uses utility analysis to assess economic and quality-of-life benefits of risperidone in patients with chronic schizophrenia. A retrospective analysis was performed on Positive and Negative Syndrome Symptoms (PANSS) data obtained from the published Canadian multicenter risperidone trial (part of the North American trial). Cluster analysis applied to endpoint PANSS scores, including all patients (N = 135), identified three clusters representing 130 patients with mild, moderate, and severe symptomatology. A narrative health state profile was written for each cluster, and 100 psychiatric nurses from Washington, DC, were asked to assign preference ratings to each one using linear analog and standard gamble (SG) methods. Mean utility values (confidence interval 95%) obtained from the SG ratings for the three health state profiles were 0.61 +/- 0.069 (mild); 0.36 +/- 0.073 (moderate); and 0.29 +/- 0.071 (severe). The mild health state (including the majority of risperidone 6 mg-treated patients) was rated by nurses to have a 0.25 +/- 0.0501 greater utility than the moderate health state (composed of the majority of haloperidol-treated patients). The results of these utility evaluations (SG) by the nurses were related to the clinical outcome for three of the six drug treatment groups (N = 65) by multiplying the percentage of patients in each of the three clusters, both at baseline and end-point, who were receiving risperidone 6 mg/day, haloperidol, or placebo, by the utility value for the health state assigned to that cluster. The gain in utility for risperidone-treated patients was 2.6 times higher (0.125) compared with haloperidol-treated patients (0.049), and 7 times higher compared with placebo (-0.021). After multiplying the gain in utility of each treatment by the remaining expected life span for men and women, it was found that risperidone-treated patients obtained more than twice as many quality-adjusted years as haloperidol patients. The incremental drug treatment cost divided by the incremental benefit of risperidone versus haloperidol was found to yield a favorable, generally accepted cost-utility ratio.
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