Savoxepine versus haloperidol. Reasons for a failed controlled clinical trial in patients with an acute episode of schizophrenia.

Savoxepine, an atypical neuroleptic compound developed in the 1980s, was believed to act via selective limbic dopamine D(2)-receptor blockade. The results of the presented double-blind, randomised, controlled clinical trial comparing savoxepine (n = 58) with haloperidol (n = 29) did not confirm the preclinical data suggesting that savoxepine would produce fewer extrapyramidal symptoms than the comparator. Animal data and PET-results obtained a posteriori suggested that this unfavourable outcome may have been due to the conventional, step-wise dose increase strategy used in the study leading to a high dopamine D(2)-receptor occupancy in the striatum thus eliciting EPS.

The development of study exit criteria for evaluating antimanic compounds.

Background: There is increasing interest on the part of investigators and the public at large in finding ways to study and improve treatments for the seriously mentally ill without exposing such individuals to unnecessary risks. One group of particular interest in this regard are patients suffering from acute mania. We set out to define "exit" criteria or novel clinical endpoints that might help to assess the efficacy of antimanic compounds.

Savoxepine: striatal dopamine-D2 receptor occupancy in human volunteers measured using positron emission tomography (PET).

The extent and duration of striatal dopamine-D2 receptor occupancy by savoxepine in humans has been studied using positron emission tomography with [11C]-raclopride, in order to investigate why the anticipated favourable ratio between its extrapyramidal and antipsychotic effects was not achieved in practice. After 0.25 mg savoxepine, striatal D2 receptor occupancy peaked at 50-60% after 24-36 h and disappeared within 6 days.

[Comparative study of changes in electroencephalographic and rheoencephalographic recordings with advancing age (author's transl)].

The correlation between the frequency index of the left parietotemporal E.E.G.

[Influence of the computed tomography in brain disorders. Retrospective study of 10,000 investigations (author's transl)].

On the basis of 10,000 examinations conducted over a period of 4 years and 7 weeks (1974-1979), the authors quantify the influence of computed tomography on neuroradiological diagnostic procedures. Findings during operation, at autopsy, or from follow-up over a sufficiently long period, are used to compare the diagnoses established after computed tomography with those suggested by other investigational methods. The regular increases in pathological observations demonstrates the increasingly precise selection of patients orientated towards the scanner.