Changes in sleep electroencephalogram and nocturnal hormone secretion after administration of the antidyskinetic agent sarizotan in healthy young male volunteers.

RATIONALE: Sarizotan is a 5-HT(1A) agonist with high affinity to D(3) and D(4) receptors. In animal experiments, the drug shows a strong anti-cataleptic effect and suppresses effectively dyskinesias in animal models of L: -dopa-induced dyskinesia and of tardive dyskinesia. Data from an open pilot study in patients with Parkinson's disease show clear indication of a treatment effect against L: -dopa-induced dyskinesia. OBJECTIVE: CNS-active drugs are known to modulate sleep electroencephalogram (EEG) and sleep-related hormone secretion. 5-HT(1A) agonists suppress rapid-eye movement (REM) sleep and enhance the secretion of ACTH, cortisol, prolactin and growth hormone (GH) at daytime. We hypothesised that sarizotan shares these effects. Furthermore, we were interested in the influence of sarizotan on leptin, which participates in the regulation of the energy balance and is enhanced after various psychoactive drugs. METHODS: Ten healthy male subjects were investigated twice in a double-blind, placebo-controlled crossover design. Sleep EEG and nocturnal hormone secretion of ACTH, cortisol, prolactin, GH and leptin were examined after oral administration of either placebo or 20 mg of sarizotan at night. RESULTS: After administration of sarizotan, a significant reduction of REM sleep and total sleep time in conventional sleep EEG and a significant reduction of sigma- and theta-power in spectral analysis were observed. The main effect on nocturnal hormone secretion was a significant elevation of prolactin and of ACTH in the first half of the night. CONCLUSIONS: While REM sleep was suppressed, the endocrine effects of 20 mg sarizotan at night were weak. Its sleep-endocrine profile is comparable to the effects provoked by selective 5-HT reuptake inhibitors.

Combination of clozapine and ziprasidone in treatment-resistant schizophrenia: an open clinical study.

OBJECTIVES: Therapeutic options for patients with treatment-resistant schizophrenia are limited. In such patients, combined application of atypical antipsychotic drugs is an often-used strategy. The authors tested the hypothesis that the combination of ziprasidone and clozapine would lead to an improvement in this patient group. METHODS: Nine patients with treatment-resistant schizophrenia participated in this open clinical trial and received a combination regimen of ziprasidone and clozapine. Patients had to have remained on a stable dose of clozapine for at least 6 months to ensure a reasonable opportunity to respond to clozapine monotherapy. Clinical status was evaluated at baseline, and at 3 and 6 months' follow-up using the Brief Psychiatric Rating Scale (BPRS). RESULTS: All patients completed the 6-month combination treatment. The mental state of 7 patients (77.8%) was improved and there was a significant reduction in the mean BPRS score over the 6 months treatment. The coadministration of ziprasidone in clozapine-treated patients did not result in a corresponding increase in side effects. The combination allowed a 18% reduction of the daily clozapine dose. CONCLUSION: The combined application of clozapine and ziprasidone follows a neurobiologic rationale and appears to be safe and well tolerated without increasing the risk of side effects.