Pharmacotherapy and pathophysiology of schizophrenia

Antipsychotic drugs are indispensable in the treatment of schizophrenia. They are useful in ameliorating positive symptoms as well as preventing psychotic relapses. However, there are patients who become refractory to the drug after repeated relapses. We conducted a retrospective study in fifty outpatients with paranoid schizophrenia who have been seen at our clinic for a duration of 15 years or more since their first psychotic episodes. It was found that the maintenance dose was correlated significantly with the number of previous relapses and total duration of psychotic episodes. These results suggest that repetitive psychotic relapses lead to a lower threshold for relapse and consequently require a higher antipsychotic dose for prevention. Behavioral sensitization to amphetamine may provide a model to study neuroplastic change after repeated relapses. Another limitation of antipsychotic drugs is the lack of effects in the negative symptoms. A dopamine agonist rather than a dopamine antagonist may be useful in the treatment of negative symptoms. Atypical antipsychotics may have some advantage to improve these symptoms. In addition to the dopaminergic system, glutamatergic and serotonergic systems seem to be involved in the pathophysiology of the negative symptoms of schizophrenia