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Idazoxan and Response to Typical Neuroleptics in Treatment-Resistant Schizophrenia

Comparison with the Atypical Neuroleptic, Clozapine

Published online by Cambridge University Press:  02 January 2018

Robert E. Litman ,
Tung-Ping Su ,
William Z. Potter ,
Walter W. Hong  and
David Pickar
Robert E. Litman*
Affiliation:
National Institute of Mental Health, Experimental Therapeutics Branch, Bethesda
Tung-Ping Su
Affiliation:
National Institute of Mental Health, Experimental Therapeutics Branch, Bethesda
William Z. Potter
Affiliation:
National Institute of Mental Health, Experimental Therapeutics Branch, Bethesda
Walter W. Hong
Affiliation:
National Institute of Mental Health, Experimental Therapeutics Branch, Bethesda
David Pickar
Affiliation:
National Institute of Mental Health, Experimental Therapeutics Branch, Bethesda
*
Dr R. E. Litman, National Institute of Mental Health, Experimental Therapeutics Branch, Section on Clinical Studies, NIH 10/4N212, 10 Center DR MSC 1380, Bethesda MD 20892-1380
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Abstract

Background

We investigated whether antagonism of α2 adrenergic receptors would augment treatment response in schizophrenia, by administering idazoxan, an α2 antagonist drug, to treatment-resistant patients on typical neuroleptics.

Method

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 α2 receptors augmented therapeutic response to typical neuroleptic treatment in treatment-resistant patients with schizophrenia. This antagonism may contribute to clozapine's superior antipsychotic effects.

Type
Papers
Information
The British Journal of Psychiatry , Volume 168 , Issue 5 , May 1996 , pp. 571 - 579
Copyright
Copyright © 1996 The Royal College of Psychiatrists 

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References

American Psychiatric Association (1987) Diagnostic and Statistical Manual of Mental Disorders (3rd edn, revised) (DSM–III–R). Washington, DC: APA.Google Scholar
Andreasen, N. C. (1981) The Scale for the Assessment of Negative Symptoms (SANS). Iowa City: University of Iowa.Google Scholar
Breier, A., Buchanan, R. W., Waltrip, R. W. III, et al (1994) The effect of clozapine on plasma norepinephrine: relationship to clinical efficacy. Neuropsychopharmacology, 10, 1–7.Google Scholar
Bunney, W. E. Jr. & Hamburg, D. A. (1963) Methods for reliable longitudinal assessment of behaviour. Archives of General Psychiatry, 9, 280–294.CrossRefGoogle Scholar
Davidson, M., Kahn, R. S., Stern, R. G., et al (1993) Treatment with clozapine and its effect on plasma homovanillic acid and norepinephrine concentrations in schizophrenia. Psychiatry Research, 46, 151–163.Google Scholar
Duinkerke, S. J., Botter, P. A., Janssen, A. A., et al (1993) Ritanserin, a selective 5HT21C antagonist, and negative symptoms in schizophrenia: a placebo-controlled, double-blind trial. British Journal of Psychiatry, 163, 451–455.Google Scholar
Eisenhofer, G., Goldstein, D. S., Stull, R., et al (1986) Simultaneous liquid chromatographic determination of 3,4-dihydroxyphenylglycol, catecholamines, and 3,4-dihydroxyphe-nylalanine in plasma in their responses to inhibition of monoamine oxidase. Clinical Chemistry, 32, 2030–2033.Google Scholar
Green, A. I., Alam, M. Y., Sobieraj, J. T., et al (1993) Clozapine response and plasma catecholamines and their metabolites. Psychiatry Research, 46, 139–149.CrossRefGoogle ScholarPubMed
Grenhoff, J., Nissel, M., Ferre, S., et al (1993) Noradrenergic modulation of midbrain dopamine cell firing elicited by stimulation of the locus coeruleus in the rat. Journal of Neural Transmission, 93, 11–25.CrossRefGoogle ScholarPubMed
Guy, W. (1976) ECDEU Assessment Manual for Psychopharmacology, pp. 535–543. Rockville, MD: Alcohol, Drug Abuse, and Mental Health Administration.Google Scholar
Javaid, J. I., Dekirmenjian, H., Liskevych, U., et al (1981) Fluphenazine determination in human plasma by sensitive gas chromatographic method using a nitrogen detector. Journal of Chromatographic Sciences, 19, 439.Google Scholar
Kane, J., Honigfeld, G., Singer, J., et al (1988) Clozapine for the treatment-resistant schizophrenic: a double-blind placebo comparison with chlorpromazine. Archives of General Psychiatry, 45, 789–796.Google Scholar
Karoum, F. & Neff, N. (1982) Quantitative gas chromatographymass spectrometry (GC-MS) of biogenic amines: theory and practice. In Modern Methods in Pharmacology (eds Spector, S. & Beck, N.), pp. 131–163. New York: Alan R. Liss.Google Scholar
Litman, R. E., Hong, W. W., Weissman, E. M., et al (1993) Idazoxan, an α2 antagonist, augments fluphenazine in schizophrenic patients: a pilot study. Journal of Clinical Psychopharmacology, 13, 264–267.Google Scholar
Litman, R. E., & Pickar, D. (in press) Noradrenergic systems as a target for augmenting pharmacotherapy in schizophrenia. In The New Pharmacotherapy of Schizophrenia (ed. Breier, A.). Washington, DC: APA.Google Scholar
Manji, H. (1992) G Proteins: implications for psychiatry. American Journal of Psychiatry, 149, 746–760.Google Scholar
Manji, H. Hsiao, J. H., Risby, E. D., et al (1991) The mechanisms of action of lithium. II: effects on serotonergic and noradrenergic systems in normal subjects. Archives of General Psychiatry, 48, 513–524.Google Scholar
Meltzer, H. Y. (1989) Clinical studies on the mechanism of action of clozapine: the dopamine-serotonin hypothesis of schizophrenia. Psychopharmacology, 99 (suppl.), S18–S27.CrossRefGoogle ScholarPubMed
Michel, M. C., Brodde, O. E., Schnepel, B., et al (1989) [3H]Idazoxan and some other α2-adrenergic drugs also bind with high affinity to a nonadrenergic site. Molecular Pharmacology, 35, 324–330.Google Scholar
Nicholson, A. N. & Pascoe, P. A. (1991) Presynaptic α2-adrenoceptor function and sleep in man: Studies with clonidine and idazoxan. Neuropharmacology, 30, 367–372.CrossRefGoogle Scholar
Overall, J. E. & Gorham, D. E. (1961) The Brief Psychiatric Rating Scale. Psychological Research, 10, 799–812.Google Scholar
Pickar, D. (1995) Prospects for pharmacotherapy of schizophrenia. Lancet, 345, 557–562.Google Scholar
Overall, J. E., Owen, R. R., Litman, R. E., et al (1992) Clinical and biologic response to clozapine in patients with schizophrenia: crossover comparison with fluphenazine. Archives of General Psychiatry, 49, 345–353.Google Scholar
Richelson, E. & Nelson, A. (1984) Antagonism by neuroleptics of neurotransmitter receptors of normal human brain in vitro. European Journal of Pharmacology, 103, 194–204.CrossRefGoogle ScholarPubMed
Schotte, A., Janssen, P. F. M., Megens, A. A. H. P., et al (1993) Occupancy of central neurotransmitter receptors by risperidone, clozapine and haloperidol, measured quantitative autoradiography. Brain Research, 631, 191–202.Google Scholar
Simpson, G. & Angus, J. S. W. (1970) A rating scale for extrapyramidal side-effects. Acta Psychiatrica Scandinavica, 212 (suppl.), 9–11.Google Scholar
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