Efficacy of Novel Antipsychotic Drugs in Treatment-Refractory Schizophrenia

Abstract

The Limitations in Efficacy and Side Effects of Typical Neuroleptic Drugs as Treatments for Schizophrenia are Well-known (Davis et al. 1980; Meltzer 1992). Although Major Positive Symptoms and Disorganization Remit During Neuroleptic Drug Treatment In As Many As 60%-70% of Patients with Schizophrenia, Negative symptoms, e.g., withdrawal, flat affect, and lack of initiative, usually respond only partially or not at all to these agents (Crow 1980; Meltzer and Zureick 1989; Kay and Singh 1989) and contribute significantly to caretaker burden. Despite the fact that most schizophrenic patients only have mild negative symptoms to begin with, the lack of effect of typical neuroleptic drugs on patients with severe negative symptoms is a serious problem. The social function and quality of life of patients with schizophrenia treated with typical neuroleptics is generally poor. Low employment and marital rates are evidence for the limitations of current therapy. The high rate of noncompliance with the neuroleptic drugs (Fleishhacker et al. 1994b) and the high suicide rate (9%-13% lifetime, 0.4%-0.8% per year; Drake et al. 1985) also provide evidence of the limitations of typical neuroleptic drugs in the treatment of schizophrenia. Noncompliance with typical neuroleptics is the result of many factors, including untreated psychopathol- ogy, inadequate patient preparation, and familial and environmental influences (Fleishhacker et al. 1994b). Extrapyramidal symptoms (EPS), especially akathisia, that are not adequately relieved by antiparkinsonian medication have been suggested to be the most important reason for noncompliance (Van Putten 1974). Suicide, too, is the result of many factors, and is commonly precipitated by depression and hopelessness (Drake et al. 1985). The suicide attempt rate appears to be similar in patients regardless of whether they are neuroleptic-responsive or neuroleptic-resistant (Meltzer and Okayli 1995).