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Conventional antipsychotic medications refer to those widely used and available in the United States before 1990, including the phenothiazines, butyrophenones, thioxanthenes, dibenzoxazepines, and dihydroindolones. Their common mode of action is to block dopamine D2 receptors throughout the brain, and their therapeutic activity is presumably related to such blockade in the mesolimbic system. Their widespread use, as well as the anticipated future availability of nonconventional antipsychotic agents, underlines the importance of examining research that supports use of conventional agents. This article reviews evidence for the efficacy and effectiveness of these conventional antipsychotic medications during both the acute and long-term phases of treatment for schizophrenia. The acute phase refers to the periods during which the patient experiences an acute episode of positive symptoms, with either the onset of symptoms after an asymptomatic period or a marked increase in symptoms over a baseline of less severe symptoms. Operationally, we define this phase as the first 6 to 8 weeks after onset of an episode of positive symptoms. Symptom remission is the central goal in the acute phase. The phase of long-term maintenance treatment refers to the periods during which the patient is not experiencing an acute episode as defined above. The nature of this phase varies tremendously across individuals. Some individuals are asymptomatic and relatively free of any disability; others experience persistent psychotic symptoms in addition to considerable impairment in their ability to live independently, work, and relate to others. The central goals of antipsychotic drug treatment in the long-term treatment phase are continued suppression of the acute symptoms (continuation therapy) or prevention of the occurrence of another episode of acute symptoms (maintenance or prophylactic therapy). Review Questions- What is the efficacy of conventional antipsychotics for
- relief of acute positive symptoms of schizophrenia?
- prevention of relapse and recurrence of positive symptoms?
- reduction of cognitive impairments and negative symptoms?
- What is the effectiveness of the conventional antipsychotics for
- relief of acute positive symptoms of schizophrenia?
- prevention of relapse and recurrence of positive symptoms?
- reduction of cognitive impairments and negative symptoms?
- Is there differential efficacy and effectiveness among the alternative conventional antipsychotics, including depot forms?
- What effects do conventional antipsychotics have on functional status and other nonclinical outcomes?
- What strategies can be recommended in the pharmacological treatment of individuals suffering their first acute episode of schizophrenia?
MethodsThe literature on conventional antipsychotic medications is extensive and sometimes lengthy. This literature review began with searches of PSYCLIT and MEDLINE covering the years 1966 to 1993 using key words. All references related to the following key words were requested with the "explode" command: schizophrenia "and" tranquilizing agents; schizophrenia "and" tranquilizing agents, major "or" tranquilizing agents; schizophrenia "and" clinical trials "or" comparative study "or" followup studies; schizophrenia "and" neuroleptic drugs-effective "or" efficacy drug therapy. Additional discussions with experts in the field and other key informants provided additional unpublished manuscripts and articles not obtained from the literature search. Our total search yielded 956 citations. Given the volume of literature, we largely reviewed existing reviews. Because subsequent reviews tend to update prior reviews by the same authors, and because the research questions changed over time, we decided to focus only on reviews published since 1984. Although most of the reviews we considered do not meet the minimum criteria for high quality according to Beaman (1991) -- for example, they typically lack specification of procedures used to identify and select the studies covered -- we selected a group of higher quality reviews that we judged to provide ample information about the review questions. Kane et al. (1985, 1986), Kane and Lieberman (1987), Baldessarini et al. (1988, 1990), Davis et al. (1989, 1993), Kane (1989), Schooler (1991), Kane and Marder (1993), and Bollini et al. (1994) authored these reviews. This review is organized according to the review questions. For each question, the findings and conclusions from each review are summarized. Subquestions related to the main review question are also addressed. When other reviews offer new information or present divergent findings or conclusions, they are mentioned. Citations of primary studies are reserved for questions not addressed in reviews or for the most recent studies that have not been covered by prior reviews.
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