Resistant schizophrenia: A challenge and new hopes (what is the effect of atypicals combinations?)

The goal of any drug therapy is to maximize the efficacy and to minimize adverse effects with the lowest possible dose. Antipsychotic medication is effective as a treatment of psychotic symptoms. Despite the advances in the treatment of schizophrenia, about 30% of patients partially respond or do not respond at all to psychopharmacotherapy. The treatment of refractory, or resistant psychosis continues to be a frequent and important problem in clinical practice. To date there is no universal adequate therapeutic strategy for treating these patients. Traditionally, the recommendations for managing treatment-resistant patients were a) increasing the neuroleptics dose; b) switching from existing (conventional) antipsychotic to an alternative conventional agent from a different chemical class; c) using augmentation effect by adding another psychotropic drug such as benzodiazepines, lithium or anticonvulsant agents or to combine high and low potency antipsychotic medications, and finally d) electroconvulsive therapy. Clozapine is the treatment of choice in resistant schizophrenic patients, but it remains limited by the need of weekly blood monitoring for early disclosure of agranulocytosis. Moreover, a relatively high incidence of side effects from clozapine such as sialorrhea, and daytime sedation, lead to physicians' apprehension and patients' poor compliance. Clozapine also may induce dose-dependent seizures, which complicate the treatment. The purpose of this chapter is to overview the current treatment approaches, described in the literature, which examine the efficacy of different antipsychotic therapy combinations in facing the problematic issue. We chose this topic, which is now very actual, and professional literature is full of discussions about it. Therefore, it is a subject of much controversy. In our opinion every modern psychiatrist has to be familiar with these therapeutic strategies. Methods A computerized MEDLINE literature search covering a 20-year period (1985-2005) was conducted. All pertinent papers on the subject of "atypical" antipsychotic medication combinations in the management of treatment resistant schizophrenia and schizoaffective disorder were obtained with subsequent analysis and discussion of the retrieved data. Conclusion The current pharmacotherapeutic approach to schizophrenic and schizoaffective patients, especially those who are chronic and treatment-resistant, is divided into conservative monotherapy versus polypharmacy. More and more voices are heard in the professional psychiatric world about safety and the positive effect of typical - atypical neuroleptics combination, and recently the combinations of two atypical antipsychotics.