Abstract
Clozapine, an atypical neuroleptic which is more efficacious than typical neuroleptics, elevates plasma and urinary noradrenergic indices in schizophrenia patients (Pickar et al, 1992). Since one mechanism for clozapine's noradrenergic effects may be antagonism of α2 receptors, we added idazoxan, a highly selective antagonist of α2 receptors, to stable neuroleptic treatment in double-blind, placebo controlled fashion in 17 treatment-refractory patients with schizophrenia. Symptoms significantly decreased with the addition of idazoxan to stable fluphenazine treatment, and returned back to baseline levels following discontinuation of idazoxan. Idazoxan treatment resulted in reductions (p<0.01) in global psychosis and in the Brief Psychiatric Rating Scale (BPRS) score compared to treatment with fluphenazine alone. Idazoxan reduced positive and negative symptoms (p<.05) and paranoia-suspiciousness (p>0.01) on the BPRS; changes in BPRS symptoms were correlated with idazoxan-induced changes in plasma norepinephrine (NE) in 9 patients. No effects of idazoxan on extrapyramidal symptoms, dyskinetic movements, or plasma fluphenazine levels were found. In a subgroup of 12 patients, idazoxan plus fluphenazine was as effective as clozapine in reducing symptoms of schizophrenia. These data suggest that the addition of idazoxan to stable neuroleptic treatment improves symptoms in neuroleptic-resistant schizophrenia patients. Correlations with idazoxan-induced changes in plasma NE support the hypothesis that the mechanism underlying idazoxan's therapeutic effects involves increased alpha-2 blockade. Moreover, these data suggest that potent alpha-2 blockade may be relevant to clozapine's mechanisms of action.
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Litman, R., Su, T., Hong, W. et al. Augmentation of Response to Typical Neuroleptic Treatment Using Idazoxan, an Alpha-2 Antagonist, in Patients with Schizophrenia. Neuropsychopharmacol 11, 275 (1994). https://doi.org/10.1038/sj.npp.1380172
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DOI: https://doi.org/10.1038/sj.npp.1380172