Idazoxan and Response to Typical Neuroleptics in Treatment-Resistant Schizophrenia

Abstract

BackgroundWe investigated whether antagonism of α2adrenergic receptors would augment treatment response in schizophrenia, by administering idazoxan, an α2antagonist drug, to treatment-resistant patients on typical neuroleptics.MethodSeventeen hospitalised treatment-resistant patients with DSM–III–R schizophrenia or schizoaffective disorder were studied on typical neuroleptic treatment, on treatment with idazoxan plus typical neuroleptic, and after discontinuation of idazoxan, in fixed, non-random order, and under double-blind, placebo-controlled conditions.ResultsThe addition of idazoxan to fluphenazine treatment resulted in significant reductions of global psychosis and total, positive and negative symptoms on the Brief Psychiatric Rating Scale, compared to neuroleptic treatment alone. Symptom improvement significantly correlated with idazoxan-induced changes in indices of noradrenergic function. In a subgroup of patients, idazoxan plus typical neuroleptic treatment compared favourably with clozapine treatment, when both were compared to typical neuroleptic treatment alone.ConclusionsThe antagonism of α2receptors augmented therapeutic response to typical neuroleptic treatment in treatment-resistant patients with schizophrenia. This antagonism may contribute to clozapine's superior antipsychotic effects.