Drug treatment of the negative symptoms of schizophrenia.

The traditional antipsychotics are generally poorly effective or ineffective against the negative symptoms of schizophrenia and are also associated with extensive side effects which can themselves cause or exacerbate secondary negative symptomatology. As well as having a low propensity to cause extrapyramidal side effects (EPS), the currently available, putative, atypical antipsychotics (clozapine, risperidone, sertindole, and olanzapine), developmental antipsychotics (zotepine, quetiapine and ziprasidone) and low doses of certain traditional antipsychotics, such as amisulpride and fluphenazine, have been reported to ameliorate negative symptoms in comparison with placebo or standard antipsychotics such as fluphenazine, haloperidol or perphenazine. To date, few trials have specifically examined primary negative symptomatology and it has been suggested that the improvements observed with these drugs may be related to decreases in positive symptoms and/or reduced sedation or extrapyramidal side effects. Although atypicality has been ascribed to 5-HT2/D2 antagonism, the exact pharmacological mechanism(s) underlying the efficacy of the atypical antipsychotics have not been elucidated. Many of these drugs bind to multiple other receptors and/or inhibit neurotransmitter uptake and it seems probable that some of these other pharmacological properties may also contribute to their clinical features.