Hostname: page-component-5447f9dfdb-xmf2s Total loading time: 0 Render date: 2025-07-29T19:10:00.496Z Has data issue: false hasContentIssue false
  • English
  • Français

Effect of Clozapine on d-Fenfluramine-Evoked Neuroendocrine Responses in Schizophrenia and its Relationship to Clinical Improvement

Published online by Cambridge University Press:  02 January 2018

Vivienne A. Curtis ,
Pádraig Wright ,
Adrianne Reveley ,
Robert Kerwin  and
James V. Lucey
Vivienne A. Curtis*
Affiliation:
Institute of Psychiatry, London
Pádraig Wright
Affiliation:
Institute of Psychiatry, London
Adrianne Reveley
Affiliation:
Institute of Psychiatry, London
Robert Kerwin
Affiliation:
Institute of Psychiatry, London
James V. Lucey
Affiliation:
Institute of Psychiatry, London
*
Dr Curtis, Institute of Psychiatry, De Crespigny Park, London SE5 8AF
Get access Rights & Permissions [Opens in a new window]

Abstract

Background

Clozapine is an effective antipsychotic that has high affinity for serotonin type 2 (5-HT2) receptors. The importance of 5-HT antagonism in the overall clinical efficacy of clozapine is unclear. Using a neuroendocrine strategy we tested the hypothesis that clinical response to clozapine is related to alteration in 5-HT function.

Method

Ten treatment-resistant schizophrenic subjects were treated with clozapine for a mean of 10.3 (s.e. 0.9) weeks; d-fenfluramine (DFEN) challenge tests were performed before and after treatment with concurrent clinical ratings (BPRS, SAPS, SANS) made at the time of testing.

Results

All patients showed clinical improvement following treatment with clozapine. In addition, clozapine produced a significant attenuation of prolactin (PRL) and cortisol (CRT) response to DFEN challenge. Change in symptom ratings correlated significantly with reduction in PRL response to DFEN challenge.

Conclusions

These data show that functional alterations occur in the 5-HT system following response to clozapine and lend support to studies suggesting that 5-HT is an important component to the spectrum of action of clozapine.

Information

Type
Papers
Information
The British Journal of Psychiatry , Volume 166 , Issue 5 , May 1995 , pp. 642 - 646
Copyright
Copyright © Royal College of Psychiatrists, 1995 

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

Article purchase

Temporarily unavailable

References

Altar, C. A., Wasley, A. M., Neale, R. F., et al (1986) Typical and atypical anti-psychotic occupancy of D2 and S2 receptors an autoradiographic analysis in rat brain. Brain Research Bulletin, 16, 517–525.Google Scholar
American Psychiatric Association (1987) Diagnostic and Statistical Manual of Mental Disorders (3rd edn, revised) (DSM–III–R). Washington, DC: APA.Google Scholar
Andreason, N. C. (1981a) The Scale for the Assessment of Positive Symptoms (SAPS). University of Iowa, Iowa City, Iowa.Google Scholar
Andreason, N. C. (1981b) The Scale for the Assessment of Negative Symptoms (SANS). University of Iowa, Iowa City, Iowa.Google Scholar
Baum, C. K., Tudor, R. & Landon, J. (1974) A single competitive protein-binding assay for plasma cortisol. Clinical Chemistry, 55, 147.CrossRefGoogle Scholar
Bennett, J. P., Enna, S. J., Bylund, D., et al (1979) Neurotransmitter receptors in frontal cortex of schizophrenics. Archives of General Psychiatry, 36, 927–934.CrossRefGoogle ScholarPubMed
Canton, H., Verriele, L. & Colpaert, F. C. (1990) Binding of typical and atypical antipsychotics to 5HT1c and 5HT2 sites: clozapine potently interacts with 5HT1c sites. European Journal of Pharmacology, 191, 93–96.CrossRefGoogle ScholarPubMed
Duinkerke, S. J., Botter, P. A., Jansen, A. A. I., et al (1993) Ritanserin a selective 5-HT2/1c antagonist and negative symptoms in schizophrenia. A placebo controlled double blind trial. British Journal of Psychiatry, 163, 451–455.CrossRefGoogle ScholarPubMed
Fuller, R. W. & Snoddy, H. D. (1984) Central dopamine receptors mediating pergolide-induced elevation of serum corticosterone in rats. Neuropharmacology, 23, 1389–1394.Google Scholar
Garratini, S., Mennini, T. & Samanin, R. (1987) From fenfluramine racemate to d-fenfluramine. Annals of the New York Academy of Sciences, 499, 156–166.CrossRefGoogle Scholar
Goodall, E. M., Cowen, P. J., Franklin, M., et al (1993) Ritanserin attenuates anorectic endocrine and thermic responses to d-fenfluramine in human volunteers. Psychopharmacology, 112, 461–466.Google Scholar
Invernizzi, R., Berettera, C., Garratini, S., et al (1986) d- and l-isomers of fenfluramine differ markedly in their interaction with brain serotonin and catecholamines in the rat. European Journal of Pharmacology, 20, 9–15.CrossRefGoogle Scholar
Kahn, R. S., Siever, L., Gabreil, S., et al (1992) Serotonin function in schizophrenia: effects of MCPP in schizophrenic patients and healthy subjects. Psychiatry Research, 43, 1–12.CrossRefGoogle ScholarPubMed
Kahn, R. S., Davidson, M., Siever, L., et al (1993a) Serotonin function and treatment response to clozapine in schizophrenic patients. American Journal of Psychiatry, 150, 1337–1342.Google Scholar
Kahn, R. S., Davidson, M., Knott, P., et al (1993b) Effect of neuroleptic medication on cerebrospinal fluid monoamine metabolite concentrations in schizophrenia. Archives of General Psychiatry, 50, 599–605.Google Scholar
Kane, J. M., Honigfeld, G., Singer, J., et al (1988) Clozapine for the treatment resistant schizophrenic. Archives of General Psychiatry, 45, 789–796.CrossRefGoogle ScholarPubMed
Kanton, R. E., Dudlettes, S. D. & Shulgin, A. T. (1980) S-methoxy-alpha-methyltryptamine: a hallucinogenic homolog of serotonin. Biological Psychiatry, 15, 349–352.Google Scholar
Lemus, C. Z., Lieberman, J. A., Johns, C. A., et al (1991) Hormonal responses to fenfluramine challenge in clozapine treated patients. Biological Psychiatry, 29, 691–694.Google Scholar
Lindstrom, L. H. (1985) Low HVA and normal 5HIAA levels in drug free schizophrenic patients compared to healthy volunteers: Correlations with symptomatology and family history. Psychiatry Research, 14, 265–273.Google Scholar
Meltzer, H. Y. & Fang, V. S. (1976) The effect of neuroleptics on serum prolactin of schizophrenic patients. Archives of General Psychiatry, 33, 279–286.Google Scholar
Muck-Seler, D., Jakoljevic, M. & Deanovic, Z. (1991) Platelet serotonin in subtypes of schizophrenia and depression. Psychiatry Research, 38, 105–113.Google Scholar
Nash, J. F., Meltzer, H. Y. & Gudelsky, G. A. (1988) Antagonism of serotonin receptor mediated neuroendocrine and temperature responses by atypical neuroleptics in the rat. European Journal of Pharmacology, 151, 463–469.CrossRefGoogle ScholarPubMed
Overall, J. E. & Gorham, D. R. (1962) The Brief Psychiatric Rating Scale. Psychological Research, 10, 799–812.Google Scholar
Pilowsky, L. S., Costa, D. C., Ell, P. J., et al (1992) Clozapine, single photon emission tomography and the D2 blockade hypothesis of schizophrenia. Lancet, 340, 199–202.Google Scholar
Sedvall, G., Fryo, B., Nyback, H., et al (1980) Relationships in healthy volunteers between concentrations of monoamine metabolites in cerebrospinal fluid and family history of psychiatric morbidity. Psychopharmacology, 70, 1–4.Google Scholar
Submit a response

eLetters

No eLetters have been published for this article.