EPOS: Increasing our understanding of the treatment of schizophrenia; Start of a prospective referenced cohort study of sertindole in clinical practice.

Sertindole is a new limbic-selective antipsychotic agent which has recently received marketing authorization in several countries across Europe for the treatment of schizophrenia. The experience gained in around 2200 patients treated with sertindole in controlled clinical trials has enabled optimal targeting of sertindole to those patient groups who will benefit most and who are least likely to experience adverse effects. Ultimately, it is how a new medicinal product is used in clinical practice, how it performs in everyday life, and how the patient who takes it feels and functions that determine the real benefit/risk ratio of a new medicinal product. The European Post-marketing Observational Serdolect® project (EPOS) is a post-marketing, referenced, observational, cohort, safety study in the treatment of schizophrenic patients initiated earlier this year. It is planned to recruit over 12 000 patients in two cohorts in centres throughout Europe. The aims are to provide a full safety evaluation of sertindole under marketed conditions at the relevant clinical dosage, and further, to provide epidemiological data on schizophrenic patients receiving sertindole or other treatment under the usual clinical conditions in Europe. At the moment, the study is the only one of its kind to be undertaken in schizophrenia and will provide important new data for psychiatrists around the world.

Oral administration of NNC 756--a placebo controlled PET study of D1-dopamine receptor occupancy and pharmacodynamics in man.

NNC 756 is a new benzazepine with high affinity and selectivity for D1-dopamine receptors. In a double-blind, placebo controlled, cross-over study, positron emission tomography and the radioligand [11C]SCH 23390 were used to determine central D1-dopamine receptor occupancy after a single oral dose of 80 mg NNC 756 in three healthy men. NNC 756 induced 75, 66 and 47% occupancy of D1-dopamine receptors in the putamen of at 1.5 h after drug administration and 46, 36 and 24% after 7.5 h. There was a hyperbolic relationship between the occupancy values and the serum concentrations. The Ki value for the hyperbola was 6.4 ng/ml (+/- SD 1.4). The occupancy at 1.5 h is on the same level as that shown to induce effects in animal models for prediction of antipsychotic effect. Restlessness (akathisia) appeared in two subjects and nausea in one subject at time of peak drug concentration in serum. The oral dose level of 80 mg should be appropriate to investigate the potential antipsychotic effect of NNC 756.

Risperidone versus perphenazine in the treatment of chronic schizophrenic patients with acute exacerbations.

Risperidone (RIS), a new neuroleptic with 5-HT2- and dopamine D2 receptor-blocking properties, was compared with perphenazine (PER) in a double-blind, multicentre, parallel-group study in 107 chronic schizophrenics with acute exacerbation. RIS 5-15 mg or PER 16-48 mg daily was given for 8 weeks. Psychopathology was assessed with the Positive and Negative Syndrome Scale (PANSS) and Clinical Global Impression. Seventy-eight patients completed the trial; there was an equal number of dropouts on both drugs. The mean daily dose at endpoint was 8.5 mg RIS and 28 mg PER. The reduction in total PANSS score to endpoint did not differ significantly, although there was a tendency in favour of RIS. The number of patients with predominantly negative symptoms who showed at least 20% reduction in total PANSS score was significantly larger in the RIS group. Furthermore, the number of patients showing at least 20% reduction in Brief Psychiatric Rating Scale (BPRS) score (BPRS being a subscale of PANSS) was significantly larger in the RIS group. The hostility cluster of BPRS improved more on RIS than on PER in the endpoint analysis. The overall prevalence of side effects was fairly similar in the two groups.