Multiple pharmacological mechanisms and clinical targets for neuroleptics: should a more operational classification be considered?

Publisher Website
Google Scholar
Abstract
Summary: The disinhibitory effect has long been described as a therapeutic property of some neuroleptic drugs (NL) able to improve negative symptoms.In pharmacology behavioral models indicate a functional facilitation of dopaminergic transmission. Moreover, a group of negative symptoms very similar to those improved by disinhibitory NL may be induced as a side effect by other NL. Therefore the syndrome improved by these few NL could be linked to functional hypodopaminergic modifications. The improvement of negative symptoms by these few NL is linked in the Animal and in Man to the administration of low doses. We propose that these drugs be called “energizing neuroleptics”. Recent clinical studies have answered various important questions concerning this effect: •patients with predominant negative or positive symptomatology do need different dosages of these NL; •the low doses of these energizing NL are more effective for the treatment of negative symptoms than low doses of other NL; •the energizing effect is not specific for schizophrenic patients, but can be shown if a negative syndrome is present. A subgroup of dysthymic patients could present a relatively pure hypodopaminergic syndrome. Even if anhedonic, these patients are not really depressed; we propose to call them psychasthenic. The energizing effect presents an original mecanism of action and a target “transnosological” syndrome. The corresponding group of NL should appear in the classifications alongside sedative and antihallucinatory (or antiflorid) NL.