Treatment-refractory schizophrenia.

Between one-third and one-half of the individuals who meet diagnostic criteria for schizophrenia remain actively ill despite optimal pharmacological treatment. These individuals tend to progressively deteriorate in terms of social and vocational functioning despite major public and private investments in their rehabilitation. For patients who do not respond to the first prescribed antipsychotic drug, current clinical practice is to switch to a second and a third drug, and eventually to clozapine, the only antipsychotic drug proven to be effective in treatment-refractory schizophrenia (TRS). Occasionally, two antipsychotics are given concomitantly or psychotropic drugs are added to antipsychotic drugs; however, very few empirical data exist to support this practice. Although there are many exceptions, patients who do not benefit from the first prescribed drug will not benefit from any pharmacological intervention. Therefore, efforts are under way to determine the reason for lack of response to available treatments and devise novel, more effective treatments. To be successful these efforts must result in a more specific definition of TRS, as well as in a better understanding of the illness pathophysiology and the mechanism of action of the drugs.