Fluvoxamine improves negative symptoms in treated chronic schizophrenia: An add-on double-blind, placebo-controlled study

Abstract

Although antipsychotic drugs are highly effective in alleviating positive symptoms of schizophrenia they have little impact on the negative symptoms of the illness. These symptoms, including apathy, social withdrawal, blunted affect, and motor retardation present serious obstacles to the successful rehabilitation of chronic schizophrenic patients and have been the focus of renewed interest (Crow 1980; Andreasen and Olsen 1982). The hypothesis of schizophrenia, based on a significant correlation between antipsychotic potency of neuroleptic drugs and their propensity to block dopamine receptors (Seeman et al 1976; Snyder 1976) is widely accepted, but other neurotransmitters may have a role in the pathogenesis, particularly of negative symptoms. Evidence pointing to serotonergic dysfunction in schizophrenia has accumulated. Increased plasma (Garelis et al 1975; DeLisi et ai 1981; Freedman et al 1981) and platelet (Jackman et al 1983) serotonin concentrations in chronic schizophrenics including a possible link to cortical atrophy (DeLisi et al 1981) have been reported and our group (Lerer et al 1988) found a blunted prolactin response to fenfluramine challenge in unmedicated chronic schizophrenic patients compared to normal controls. Furthermore, improvement in negative symptoms of schizophrenia has been reported as a result of treatment with serotonin active agents, fenfluramine (Stahl et al 1985), ritanserin (Gelders et al 1986) and ¢yproheptadine (Silver et al 1989). Clozapine, which appears to be effective in treatmentresistent positive and negative symptoms of chronic schizophrenia, has a high serotonergic:dopaminergic blocking ratio (Kant ct al 1988. Richelson 1984). There is little evidence that antidepressants can ameliorate negative symptoms of schizophrenia, although tricyclic and monoamine oxidase inhibiting (MAOI) antidepressants may be useful in schizophrenic patients demonstrating depressive symptoms (Siris et al 1978). However, the recently developed antidepressants such as fluvoxamine (Benfield and Ward 1986) acting specifically on the serotonergic system may be effective in treating primary negative symptoms of schizophrenia. We report the results of a doubleblind add-on study of fluvoxamine in chronic schizophrenic patients. To our knowledge this is the first such report.