Treatment of negative symptoms in schizophrenia and schizoaffective disorder by selegiline augmentation of antipsychotic medication : A pilot study examining the role of dopamine

It has been suggested that schizophrenic negative symptoms may be manifestations of regionally deficient CNS dopaminergic activity. We sought to test this hypothesis by openly treating patients on chronic antipsychotic medication who showed prominent negative symptoms with low-dose selegiline (5 mg b.i.d.), a monoamine oxidase-B inhibitor that selectively enhances dopaminergic activity. Twenty-one patients meeting DSM-III-R criteria for chronic schizophrenia (N = 14) or schizoaffective disorder (N = 7) with prominent negative symptoms were studied. Subjects had been kept at their current antipsychotic and antiparkinsonian medication dose levels for at least a month before the study, which was continued unchanged throughout the trial. Over 6 weeks of selegiline treatment, a 34.7% reduction in negative symptoms was demonstrated on the Scale for the Assessment of Negative Symptoms. There were also reductions in depressive symptoms (21-item Hamilton Depression Scale dropped 36.8%) and extrapyramidal symptoms (Simpson-Angus Extrapyramidal Symptom Scale scores dropped 27.7%), but no change was observed in the severity of positive symptoms as measured by the Brief Psychiatric Rating Scale. Global clinical improvement was demonstrated, with mean Clinical Global Impressions Scale score rising 17.6%. These findings support the hypothesis that negative symptoms, as well as extrapyramidal symptoms and certain depressive symptoms, may be manifestations of regionally deficient dopaminergic activity.