Fixed-dosed risperidone in mania: an open experimental trial.

The purpose of the study was to assess the efficacy and tolerance of risperidone in mania. Fourteen inpatients with a DSM-IV manic episode were treated with risperidone at a fixed daily dose of 6 mg for 4 weeks. Compliance was assured by weekly determinations of serum concentrations of risperidone. Ten out of the 14 patients completed all 4 weeks of treatment, and all of these achieved at least a 75% reduction on the Bech-Rafaelsen Mania Scale (MAS). On the other applied measures, a substantial improvement was also seen in most patients, and no worsening in any of the rating scales was observed in any patient. Five patients continued concomitant treatment with a mood stabilizer. When the results were compared with the results from a similar historic control group treated with the middle-potency typical antipsychotic zuclopenthixol at a daily dose of 20 mg under the same experimental conditions, a between group difference in mean percentage change (baseline versus endpoint) on the MAS was 34.7% (95% confidence interval = 7.9-61.6%) in favour of risperidone. Side-effect profiles were rather similar in the two treatment groups. Despite design limitations, these findings may justify the conduction of randomized controlled trials to investigate the use of risperidone in mania.

Clozapine serum levels and side effects during steady state treatment of schizophrenic patients: a cross-sectional study.

Serum clozapine (S-Cloza) and serum desmethyl-clozapine concentrations (S-Descloza) were measured in 30 chronic schizophrenic in- and out-patients on a variable dose regimen. All patients were in steady state with respect to clozapine therapy and in a stable condition with respect to psychotic illness. The 24-h clozapine dose (median with interquartile range in parenthesis) was 350 (228-425) mg/24 h (range 100-700). There was a weak positive correlation between doses and the BPRS total score (r = 0.44, P < 0.05). The median S-Cloza was 1076 (706-1882) nmol/l (range 196-5581 corresponding to 64-1824 ng/ml). The S-Cloza was linearly correlated to dose but with a high interindividual variation at equal doses, e.g. a factor of 8 at 400 mg/24 h, but a low intraindividual variability of 20%. The S-Descloza averaged 77% of the S-Cloza and was highly correlated to S-Cloza (r = 0.90; P < 0.001). The S-Descloza/dose ratio increased with age and duration of treatment. The side effects registered were EEG abnormalities (83%), tachycardia (23%), increased liver enzyme activity (60%), orthostatic hypotension (17%), and moderate leucocytosis (17%). Only EEG changes were correlated to S-Cloza (r = 0.43; P < 0.05). The score values of the UKU Side Effect Scale were weakly (r = 0.36) correlated to S-Cloza. No side effects were correlated to S-Descloza, doses, or treatment duration. The frequency of side effects was higher than in studies using lower mean doses indicating a correlation between doses or S-Cloza and the frequency of side effects. It is concluded that clozapine fulfils the criteria for therapeutic drug monitoring. TDM may contribute to finding the lowest effective dose with the fewest possible side effects.