Pharmacotherapy of schizophrenic patients: achievements, unsolved needs, future research necessities

Schizophrenia is a severe mental disorder, characterized by a complex symptomatology and a chronic relapsing course, leading to a more or less intensive residual syndrome. The disorder has strong consequences on social functioning and on the patients' quality of life and is associated with a huge economical burden for the society. The best possible drug treatment should be therefore provided. The introduction of the FGAs was an important step forward, since they were the first specific drug treatment for schizophrenia in the first place. However, the positive therapeutic effect was counterbalanced by problematic side-effects, predominantly different kinds of EPS. The SGAs have a much lower liability to induce EPS, with clozapine inducing no EPS. Additionally, SGAs demonstrated some advantages in terms of a broader spectrum of efficacy, including e.g. negative symptoms. However, for most of the single compounds this efficacy advantage was not as high as initially expected. Thus, there is a need for new developments. Currently, drugs in development are based on the classical transmitter related approaches, following especially the model of clozapine and several other multi-receptor compounds. More and more, the glutamatergic system is of interest in this context as well. Totally new directions, e.g. based on genetic findings or focussing more on brain plasticity are headed for. The question is, whether beside the classical concept of antipsychotics, which covers all symptomatic domains of schizophrenia, compounds demonstrating efficacy only in one syndrome such as e.g. negative symptoms will have a chance in the future development.