Treatment of schizophrenia is a moving target

In the course of the last 60 years, pharmacological treatment of schizophrenia focused on varying targets. Chlorpromazine, originally an antihistaminic compound, found its main use in psychiatry because of its sedative properties. Non - specific sedation reduced the agitation of psychotic patients. It took forty years before the sedation related term „neuroleptics“ for drugs that treat psychosis, has been replaced by the more appropriate term „antipsychotics“. The confidence with which we are using antipsychotics may be well served by a sobering review of changes in the indications of these drugs and changes of the knowledge on their mechanism of action. The concept of schizophrenia itself has changed considerably. Today, it is a less popular concept with a narrower meaning, than it used to be at the time of the introduction of neuroleptics. The change in the social context of treatment also influenced targeting of pharmacotherapy in schizophrenia growing respect for human individuality meant greater attention to patient´s subjective experience, his compliance with treatment and to his attitude to medication. Effectivness replaced efficacy as an outcome measure in trials of antipsychotic drugs. Large scale pragmatic trials like CATIE or EUFEST provide for measurement of the effectivness better than methodically correct head to head trials of antipsychotics. The increasing knowledge on the mechanism of action in neuroleptics significantly helped to elucidate the biological underpinnings of schizophrenic psychosis. On the other hand, neuroleptics as well as new antipsychotics have been also used in the treatment of disorders, that only hardly have any pathogenic links with schizophrenia. Also, the expectation of the main effects of pharmacotherapy in psychosis has changed: instead of an effect on agitation, we expect an effect on cognitive and negative symptoms. In the past, negative symptoms were often thought of as necessary correlates of the neuroleptic action in psychosis. Recently, it has been also reported, that the interaction of a drug with the dopamine receptor is not a necessary condition for an antipsychotic effect. This supports the idea that schizophrenia need not necessarily be associated with the dopamine mediated control of stimuli´s salience. Treatment of schizophrenia and corresponding rules vary over time, which may mask the lasting positive changes in the therapeutic approach to psychosis.

Keywords: Key words: schizophrenia, psychosis, antipsychotics, dopaminergic neurotransfer, the effectiveness of the treatment, pragmatic pharmacological studies.