Selegiline in the Treatment of Negative Symptoms of Schizophrenia

Abstract

Key words: Selegiline; schizophrenia; negative symptoms; neurotherapeutics; clinical trial. Introduction and Overview One of the great successes of modern psychiatry was the introduction of antipsychotic drugs over 50 years ago (Ayd & Blackwell, 1970). The impressive effectiveness of these agents in relieving florid positive symptoms of schizophrenia has permitted a whole population of formerly institutionalized patients to live in the community. Unfortunately, this great benefit has not been matched by the effect of antipsychotic drugs on the negative symptoms of schizophrenia, which so limit the daily function of these patients, and classical neuroleptics often worsened these symptoms. More recently, atypical antipsychotics have shown improved properties in this regard, but negative symptoms remain the least medication-responsive features of chronic schizophrenia. The impoverishment of emotion and initiative that underlie negative symptoms resemble symptoms affecting patients with Parkinson's disease, as well as the pseudo-parkinsonian effects of first-generation antipsychotics, and has been hypothesized to reflect specific deficits in the functioning of dopaminergic pathways (Bermanzohn & Siris, 1992; Davis et al ., 1991). Selegiline (formerly 1-depreny1) is a dopamine enhancing antiparkinsonian drug (Knoll, 1983), which acts as a selective monoamine oxidase type B (MAO-B) inhibitor without the clinical toxicities that have limited the use of non-selective MAO inhibitors (MAOIs) in psychiatry. The potential of selegiline to alleviate some of the parkinsonian-like emotional deficits of schizo-phrenics has led to a series of investigations of its use as a specific remedy for negative symptoms over the past 15 years.