Treatment of Negative Symptoms in Schizophrenia and Schizoaffective Disorder by Selegiline Augmentation of Antipsychotic Medication

Abstract

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.

Treatments for schizophrenia: a critical review of pharmacology and mechanisms of action of antipsychotic drugs

“…Selegiline (deprenyl) is a monoamine oxidase (MAO)-B inhibitor that selectively enhances Although several case series reported the beneficial effects of selegiline on negative symptoms of schizophrenia, [342][343][344] one double-blind, controlled study of the agent as adjunct to antipsychotic treatment failed to offer therapeutic benefit. 345 The selective irreversible MAO-B inhibitors, selegiline and rasagiline, have been shown to possess neuroprotective activities in cell culture and in vivo models of Parkinson's disease (for a review, see Maruyama et al 346 ).…”

Depression in Schizophrenia: Perspective in the Era of “Atypical” Antipsychotic Agents

“…Adjunctive monoamine oxidase inhibitors (MAOIs) might also be useful for depression in schizophrenia, although the literature is sparse (142). It is of further interest that there have been some encouraging results involving adjunctive SSRIs (140,141,(143)(144)(145)(146)(147), MAOIs (141,(148)(149)(150), and trazodone (151) in double-blind trials treating negative symptoms in schizophrenia. No prospective randomized study has yet been published, however, involving an adjunctive antidepressant added to an atypical antipsychotic agent in depressed patients with schizophrenia.…”

Monoamine oxidase inhibitors: Promising therapeutic agents for Alzheimer’s disease (Review)

“…The enzyme preferentially degrades benzylamine and phenylethylamine and targets a wide variety of specific neurotransmitters involved in the primary substrates of MAO in the brain, including epinephrine (EP), norepinephrine (NE), dopamine (DA), serotonin (5-HT), and β-phenylethylamine (PEA) (1,2). The unique position of MAO in modulating the function of a diverse series of specific neurotransmitters in association with various conditions, including mood disorders (3), anxiety and depression (4,5), schizophrenia (6), attention deficit hyperactivity disorder (7)(8)(9), migraine (10), sexual maturation (11) and neurodegenerative diseases (12), has attracted significant attention to the protein as a therapeutic target.…”