IDAZOXAN AND RESPONSE TO TYPICAL NEUROLEPTICS IN TREATMENT-RESISTANT SCHIZOPHRENIA - COMPARISON WITH THE ATYPICAL NEUROLEPTIC, CLOZAPINE

Background. We investigated whether antagonism of alpha(2) adrenergic receptors would augment treatment response in schizophrenia, by admini stering idazoxan, an alpha(2) antagonist drug, to treatment-resistant patients on typical neuroleptics. Method, Seventeen hospitalised treat ment-resistant patients with DSM-III-R schizophrenia or schizoaffectiv e 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. Results. The addition of idazoxan to fluphenazi ne treatment resulted in significant reductions of global psychosis an d total, positive and negative symptoms on the Brief Psychiatric Ratin g Scale. compared to neuroleptic treatment alone. Symptom improvement significantly correlated with idazoxan-induced changes in indices of n oradrenergic function. In a subgroup of patients, idazoxan plus typica l neuroleptic treatment compared favourably with clozapine treatment, when both were compared to typical neuroleptic treatment alone. Conclu sions. The antagonism of alpha(2) receptors augmented therapeutic resp onse to typical neuroleptic treatment in treatment-resistant patients with schizophrenia. This antagonism may contribute to clozapine's supe rior antipsychotic effects.