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 administering idazoxan, an alpha 2 antagonist drug, to treatment-resistant patients on typical neuroleptics.


METHODS
Seventeen 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.


RESULTS
The 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.


CONCLUSIONS
The antagonism of alpha 2 receptors augmented therapeutic response to typical neuroleptic treatment in treatment-resistant patients with schizophrenia. This antagonism may contribute to clozapine's superior antipsychotic effects.
Litman
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National Institute of Mental Health, Experimental Therapeutics Branch, Bethesda MD 20892-1380, USA.
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Potter
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D000317:Adrenergic alpha-Antagonists / Q000008:administration & dosage*; D000328:Adult; D014150:Antipsychotic Agents / Q000008:administration & dosage* / Q000009:adverse effects; D003024:Clozapine / Q000008:administration & dosage* / Q000009:adverse effects; D004146:Dioxanes / Q000008:administration & dosage* / Q000009:adverse effects; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D005260:Female; D005476:Fluphenazine / Q000008:administration & dosage / Q000009:adverse effects; D006801:Humans; D019329:Idazoxan; D007093:Imidazoles / Q000008:administration & dosage* / Q000009:adverse effects; D008297:Male; D008875:Middle Aged; D011569:Psychiatric Status Rating Scales; D012559:Schizophrenia / Q000175:diagnosis / Q000188:drug therapy*; D012565:Schizophrenic Psychology; D016896:Treatment Outcome
D000317:Adrenergic alpha-Antagonists; D014150:Antipsychotic Agents; D004146:Dioxanes; D007093:Imidazoles; D003024:Clozapine; D005476:Fluphenazine; D019329:Idazoxan