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The dopamine-serotonin relationship in clozapine response

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Abstract

The effects of clozapine on the dopamine and serotonin systems may underlie its atypical pharmacologic and clinical profile. To examine this hypothesis, we measured dopamine and serotonin plasma and cerebrospinal (CSF) metabolites and the relationship of these values to treatment response in 19 neuroleptic refractory and intolerant schizophrenic patients. Only a small change in the CSF and plasma homovanillic acid (HVA) and 5-hydroxyindoleacetic acid (5HIAA) levels was found. However, the pretreatment CSF HVA/5HIAA ratio and, to a lesser extent, the CSF HVA level predicted treatment response. These results suggest that the modest relationship between HVA and 5-HIAA and treatment response supports the involvement of both neurotransmitters in the pathophysiology of schizophrenia.

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References

  • Achenheil M, Blatt B, Lampart C (1975) Effect of clozapine on 5HIAA excretion in urine and CSF of psychotic patients and on serotonin metabolism in rat brain. Acta Vitaminol Enzymol 29:79–81

    PubMed  Google Scholar 

  • Agren H, Mefford IN, Rudorfen MV, Linnoila M, Potter WZ (1986) Interacting neurotransmitter systems. A non-experimental approach to the 5-HIAA-HVA correlation in human CSF. J Psychiatr Res 20:175–193

    Article  PubMed  Google Scholar 

  • Bartholini G, Halfely W, Jalfre M, Keller HH, Pletscher A (1972) Effect of clozapine on cerebral catecholominergic neurone systems. Br J Pharmacol 46:736–740

    PubMed  Google Scholar 

  • Deutsch AG, Moghaddam B, Innis R, Krystal JH, Aghajanian GK, Bunney BS, Charney DS (1991) Mechanisms of action of atypical antipsychotic drugs. Implications for novel therapeutic strategies for schizophrenia. Schizophr Res 4:121–156

    Article  PubMed  Google Scholar 

  • Fri CG, Wiesel FA, Sedvall G (1974) Simultaneous quantification of homovanillic acid and 5-hydroxyindoleacetic acid in cerebrospinal fluid by mass fragmentography. Life Sci 14:2469–2480

    Article  PubMed  Google Scholar 

  • Friedman RL, Sanders-Bush E, Barett RL (1985) Clozapine blocks disruptive and discriminative stimulus effects of quipazine. Eur J Pharmacol 106:191–193

    Article  Google Scholar 

  • Gerlach J, Thorsen K, Fog R (1975) Extrapyramidal reactions and amino metabolites in cerebrospinal fluid during haloperidol and clozapine treatment of schizophrenic patients. Psychopharmacology 40:341–350

    Article  Google Scholar 

  • Guy W (1976) Clinical Global Impression Scale. In: EDCEU Assessment Manual. US Department of Health Education and Welfare, pp 218–222

  • Honigfeld G, Paten J, Singer J (1984) Clozapine: antipsychotic activity in treatment-resistant schizophrenics. Adv Ther 1:77–97

    Google Scholar 

  • Kane J, Honigfeld G, Singer J, Meltzer H (1988) Clozapine for the treatment-resistant schizophrenic: a double-blind comparison versus chlorpromazine/benztropine. Arch Gen Psychiatry 45:789–796

    PubMed  Google Scholar 

  • Lieberman JA, Saltz BL, Johns CA, Pollock S, Kane JM (1984) Clozapine effects on tardive dyskinesia. Psychopharmacol Bull 25:57–62

    Google Scholar 

  • Meltzer HY, Bastoni B, Ramirez L, Matsurbara S (1989a) Clozapine: new research on efficacy and mechanism of action. Eur Arch Psychiatry Neurol Sci 238:332–339

    Article  PubMed  Google Scholar 

  • Meltzer HY (1989b) Clinical studies on the mechanism of action of clozapine: the dopamine-serotonin hypothesis of schizophrenia. Psychopharmacology 99:518–527

    Article  Google Scholar 

  • Pickar D, Owen RR, Litman RE, Konicki E, Gutierrez R, Rapaport MH (1992) Clinical and biologic response to clozapine in patients with schizophrenia. Arch Gen Psychiatry 49:345–353

    PubMed  Google Scholar 

  • Simpson GM, Cooper TD (1978) Clozapine plasma levels and convulsions. Am J Psychiatry 135:99–100

    PubMed  Google Scholar 

  • Simpson GM, Lee JH, Zoubek B (1979) A rating scale for tardive dyskinesia. Psychopharmacology 64:171–179

    Article  PubMed  Google Scholar 

  • Woerner MG, Mannuzza S, Kane JM (1988) Anchoring the Brief Psychiatric Rating Scale; an aid to improve reliability. Psychopharmacol Bull 24:112–117

    PubMed  Google Scholar 

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Szymanski, S., Lieberman, J., Pollack, S. et al. The dopamine-serotonin relationship in clozapine response. Psychopharmacology 112 (Suppl 1), S85–S89 (1993). https://doi.org/10.1007/BF02245011

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