Effects of Antipsychotic Agents on Symptoms of Schizophrenia
Antipsychotic agents have a specific effect on positive symptoms of schizophrenia including hallucinations, delusions and thought disorder (Hirsch and Barnes, 1995). First-generation antipsy-chotic drugs (e.g., chlorpromazine and haloperidol) are effective for alleviating positive symptoms and in preventing their recur-rence in many schizophrenic patients (Miyamoto et al., 2000, 2002a).
Although the proportion of patients who improve and the magnitude of therapeutic effects vary greatly, second-generation antipsychotics appear to be at least as effective for psychotic symptoms as conventional drugs (Markowitz et al., 1999; Remington and Kapur, 2000).
Within a short period of time, clozapine, risperidone, olanzapine, quetiapine and ziprasidone have become the drugs of choice over conventional antipsychotic drugs in the treatment of schizophrenia and schizoaffective disorder (Buckley, 2001). There is, however, still considerable debate with regard to the clinical superiority of second-generation over conventional antipsychotics. The CATIE study (Lieberman, 2005) failed to resolve this debate, with all medications tested demonstrating comparable clinical efficacy.
Negative symptoms can be divided into three components that are usually difficult to distinguish: 1) primary or deficit-enduring negative symptoms, 2) primary nonenduring negative symptoms, and 3) secondary negative symptoms that may be associated with positive symptoms, EPS, depression and environmental depriva-tion (Buchanan and Gold, 1996; Collaborative Working Group on Clinical Trial Evaluations, 1998a). Studies of the early course of illness have shown that about 70% of schizophrenics develop pri-mary negative symptoms, such as affective blunting, emotional withdrawal, poverty of speech, anhedonia and apathy, before the onset of positive symptoms (Hafner et al., 1992). Negative symptoms may represent core features of the illness, and may be associated with poor outcome and prolonged hospitalization for patients (Buchanan and Gold, 1996).
Conventional antipsychotics are generally less effective against negative than positive symptoms of schizophrenia (Miyamoto et al., 2002a). Thus, the efficacy of second-generation antipsychotics on negative symptoms compared with that of first-generation drugs has received much attention. Although second-generation antipsychotics have been shown to be more effective than conventional agents in treating negative symptoms, there is a continuing debate as to whether these effects are related to a reduction in EPS, or to a direct effect on primary negative symptoms (Marder and Meibach, 1994; Kane et al., 2001; Remington and Kapur, 2000; Carpenter et al., 1995; Conley et al., 1994; Meltzer, 1995).
A summary of the clinical profile of second-generation drugs on a range of symptoms is provided in Table 77.3.
Depressive symptoms frequently occur in the context of psy-chotic symptoms or intercurrently between psychotic episodes (Siris, 2001). Antidepressant medication used adjunctively to antipsychotic drugs is generally indicated and effective (Siris, 2001). Atypical antidepressants have been reported to have se-lective benefits against mood symptoms in schizophrenia, both manic and depressive (Sartorius et al., 2002).
Suicidal behavior presents a particular problem in patients with schizophrenia. Recently the FDA approved clozapine for use in suicidal patients with schizophrenia on the basis of results in the InterSePT study. This study found that clozapine treatment produced a lower rate of suicidal behavior than the comparison treatment olanzapine in patients with active or histories of sui-cidal behavior (Meltzer et al., 2003).