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January 1991, Vol 48, No. 1 >
Article | January 1991

Changes in Plasma Homovanillic Acid Concentrations in Schizophrenic Patients Following Neuroleptic Discontinuation

Michael Davidson, MD; Renë S. Kahn, MD; Peter Powchik, MD; Patricia Warne, PhD; Miklos F. Losonczy, MD, PhD; Rami Kaminsky, MD; Seth Apter, MA; Stacey Jaff; Kenneth L. Davis, MD
[+] Author Affiliations

Accepted for publication June 24, 1990.

Reprint requests to Department of Psychiatry, Bronx Veterans Affairs Medical Center, Psychiatry Service (116A), 130 W Kingsbridge Rd, Bronx, NY 10468 (Dr Davidson).


Arch Gen Psychiatry. 1991;48(1):73-76. doi:10.1001/archpsyc.1991.01810250075011
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• Changes in plasma levels of the dopamine metabolite homovanillic acid have been reported to correlate with changes in the severity of schizophrenic symptoms during neuroleptic administration and after neuroleptic discontinuation. This study examined the effects of discontinuation of neuroleptic treatment on plasma homovanillic acid levels in 23 patients with chronic schizophrenia. It was hypothesized that clinical decompensation would be associated with increased plasma homovanillic acid levels. Plasma homovanillic acid was measured during administration of neuroleptic medication and during a subsequent 6-week drug-free period. Nine patients decompensated during the drug-free period and 14 patients did not. Following drug discontinuation, plasma homovanillic acid concentrations were higher in schizophrenic patients who decompensated than in those who did not. Furthermore, peak plasma homovanillic acid elevation after discontinuation of neuroleptic medication was significantly correlated with peak Brief Psychiatric Rating Scale increase. The data suggest that, in some schizophrenic patients, symptomatic decompensation after discontinuation of neuroleptic treatment is associated with increases in dopamine turnover.

REFERENCES

1 +
Kendler KS, Davis KL.  Acute and chronic effects of neuroleptic drugs on plasma and brain homovanillic acid in the rat . Psychiatr Res . 1984;;13:51-56.
2 +
Davidson M, Losonczy MF, Mohs RC, Lesser JC, Powchik P, Freed LB, Davis BM, Mykytyn VV, Davis KL.  Effects of debrisoquin and haloperidol on plasma homovanillic acid concentration in schizophrenic patients . Neuropsychopharmacology . 1987;;1:17-23.
3 +
Bacopoulos NG, Hattox SE, Roth RH.  3,4 Dihydroxyphenylacetic acid and homovanillic acid in rat plasma: possible indicators of dopaminergic activity . Eur J Pharmacol . 1979;;56:225-236.
4 +
Kopin I, Bankiewicz KS, Harvey-White J.  Assessment of brain dopamine metabolism from plasma HVA and MHPG during debrisoquin treatment: validation in monkeys treated with MPTP . Neuropsychopharmacology . 1988;;1:119-126.
5 +
Maas JW, Contreras SA, Seleshi E, Bowden CL.  Dopamine metabolism and disposition in schizophrenic patients . Arch Gen Psychiatry . 1988;;45:553-560.
6 +
Davila R, Manero E, Zumarraga Andia I, Schweitzer JW, Friedhoff AJ.  Plasma homovanillic acid as a predictor of response to neuroleptics . Arch Gen Psychiatry . 1988;;45:564-567.
7 +
Bunney BS, Grace AA.  Acute and chronic haloperidol treatments: comparison of effects on nigral dopaminergic cell activity . Life Sci . 1983;;32:983-993.
8 +
Pickar D, Labarca R, Doran A, Wolkowitz OM, Roy A, Breier A, Linnoila M, Paul SM.  Longitudinal measurement of plasma homovanillic acid levels in schizophrenic patients . Arch Gen Psychiatry . 1986;;43:669-676.
9 +
Bowers MB, Swigar ME, Jatlow PI, Hoffman FJ.  Plasma catecholamine metabolites and treatment response at neuroleptic state . Biol Psychiatry . 1989;;25:734-738.
10 +
Bunney BS, Sesack SR, Silva NL.  Midbrain dopaminergic systems: neurophysiology and electrophysiological pharmacology . In: Meltzer HY, ed. Psychopharmacology: The Third Generation of Progress . New York, NY: Raven Press; 1987;:113-126.
11 +
Bowers MB, Swigar ME, Jatlow PI, Goicoechea N.  Plasma catecholamine metabolism and early response to haloperidol . J Clin Psychiatry . 1984;;45:248-251.
12 +
Davis KL, Davidson M, Mohs RC, Kendler KS, Davis BM, Johns CA, DeNigris Y, Horvath TB.  Plasma homovanillic acid concentration and the severity of schizophrenic illness . Science . 1985;;227:1601-1602.
13 +
Davidson M, Davis KL.  A comparison of plasma homovanillic acid concentrations in schizophrenics and normal controls . Arch Gen Psychiatry . 1988;;45:561-563.
14 +
Van Putten TH, Marder S, Aravagiri M, Chabert N, Mintz J.  Plasma homovanillic acid as a predictor of response to fluphenazine treatment . Psychopharmacol Bull . 1989;;40:89-91.
15 +
Sharma R, Javaid JI, Janicak PH, Faull K, Comaty J, Davis JM.  Plasma and CSF HVA before and after pharmacological treatment . Psychiatr Res . 1989;;28:97-104.
16 +
Glazer WM, Bowers MB, Charney DS, Heninger GR.  The effect of neuroleptic discontinuation on psychopathology, involuntary movements, and biochemical measures in patients with persistent tardive dyskinesia . Biol Psychiatry . 1989;;26:224-233.
17 +
Endicott F, Spitzer RL.  A diagnostic interview: the schedule for affective disorders and schizophrenia . Arch Gen Psychiatry . 1987;;35:837-844.
18 +
Davidson M, Giordani A, Mohs RC, Aryan T, Davis KL.  Control of extraneous factors affecting plasma homovanillic acid concentrations . Psychiatr Res . 1987;;20:307-312.
19 +
Lieberman JA, Kane JM, Sarantakos S, Gadaleta D, Woerner M, Alvir J, Ramos-Lorenzi J.  Prediction of relapse in schizophrenia . Arch Gen Psychiatry . 1987;;44:597-603.
20 +
Kirch DG, Jaskiw G, Linnoila M, Wienberger DR, Wyatt RJ.  Plasma amine metabolites before and after withdrawal from neuroleptic treatment in chronic schizophrenic inpatients . Psychiatr Res . 1988;;25:233-242.
21 +
Kopin IJ.  Catecholamine metabolism: basic aspects and clinical significane . Pharmacol Rev . 1985;;37:333-364.
22 +
Curet O, Dennis T, Scatton B.  The formation of deaminated metabolites of dopamine in the locus coeruleus depends upon noradrenergic activity . Brain Res . 1985;;335:297-301.
23 +
Favre R de Haut M, Dalmaz JM, Pequignot JM, Peyrin L.  Peripheral distribution of free dopamine and its metabolites in the rat . J Neural Transm . 1986;;66:135-149.
24 +
Potter WZ, Hsiao JK, Goldman SM.  Effects of renal clearance on plasma concentrations of homovanillic acid: methodologic cautions . Arch Gen Psychiatry . 1989;;46:558-564.

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1 +
Kendler KS, Davis KL.  Acute and chronic effects of neuroleptic drugs on plasma and brain homovanillic acid in the rat . Psychiatr Res . 1984;;13:51-56.
2 +
Davidson M, Losonczy MF, Mohs RC, Lesser JC, Powchik P, Freed LB, Davis BM, Mykytyn VV, Davis KL.  Effects of debrisoquin and haloperidol on plasma homovanillic acid concentration in schizophrenic patients . Neuropsychopharmacology . 1987;;1:17-23.
3 +
Bacopoulos NG, Hattox SE, Roth RH.  3,4 Dihydroxyphenylacetic acid and homovanillic acid in rat plasma: possible indicators of dopaminergic activity . Eur J Pharmacol . 1979;;56:225-236.
4 +
Kopin I, Bankiewicz KS, Harvey-White J.  Assessment of brain dopamine metabolism from plasma HVA and MHPG during debrisoquin treatment: validation in monkeys treated with MPTP . Neuropsychopharmacology . 1988;;1:119-126.
5 +
Maas JW, Contreras SA, Seleshi E, Bowden CL.  Dopamine metabolism and disposition in schizophrenic patients . Arch Gen Psychiatry . 1988;;45:553-560.
6 +
Davila R, Manero E, Zumarraga Andia I, Schweitzer JW, Friedhoff AJ.  Plasma homovanillic acid as a predictor of response to neuroleptics . Arch Gen Psychiatry . 1988;;45:564-567.
7 +
Bunney BS, Grace AA.  Acute and chronic haloperidol treatments: comparison of effects on nigral dopaminergic cell activity . Life Sci . 1983;;32:983-993.
8 +
Pickar D, Labarca R, Doran A, Wolkowitz OM, Roy A, Breier A, Linnoila M, Paul SM.  Longitudinal measurement of plasma homovanillic acid levels in schizophrenic patients . Arch Gen Psychiatry . 1986;;43:669-676.
9 +
Bowers MB, Swigar ME, Jatlow PI, Hoffman FJ.  Plasma catecholamine metabolites and treatment response at neuroleptic state . Biol Psychiatry . 1989;;25:734-738.
10 +
Bunney BS, Sesack SR, Silva NL.  Midbrain dopaminergic systems: neurophysiology and electrophysiological pharmacology . In: Meltzer HY, ed. Psychopharmacology: The Third Generation of Progress . New York, NY: Raven Press; 1987;:113-126.
11 +
Bowers MB, Swigar ME, Jatlow PI, Goicoechea N.  Plasma catecholamine metabolism and early response to haloperidol . J Clin Psychiatry . 1984;;45:248-251.
12 +
Davis KL, Davidson M, Mohs RC, Kendler KS, Davis BM, Johns CA, DeNigris Y, Horvath TB.  Plasma homovanillic acid concentration and the severity of schizophrenic illness . Science . 1985;;227:1601-1602.
13 +
Davidson M, Davis KL.  A comparison of plasma homovanillic acid concentrations in schizophrenics and normal controls . Arch Gen Psychiatry . 1988;;45:561-563.
14 +
Van Putten TH, Marder S, Aravagiri M, Chabert N, Mintz J.  Plasma homovanillic acid as a predictor of response to fluphenazine treatment . Psychopharmacol Bull . 1989;;40:89-91.
15 +
Sharma R, Javaid JI, Janicak PH, Faull K, Comaty J, Davis JM.  Plasma and CSF HVA before and after pharmacological treatment . Psychiatr Res . 1989;;28:97-104.
16 +
Glazer WM, Bowers MB, Charney DS, Heninger GR.  The effect of neuroleptic discontinuation on psychopathology, involuntary movements, and biochemical measures in patients with persistent tardive dyskinesia . Biol Psychiatry . 1989;;26:224-233.
17 +
Endicott F, Spitzer RL.  A diagnostic interview: the schedule for affective disorders and schizophrenia . Arch Gen Psychiatry . 1987;;35:837-844.
18 +
Davidson M, Giordani A, Mohs RC, Aryan T, Davis KL.  Control of extraneous factors affecting plasma homovanillic acid concentrations . Psychiatr Res . 1987;;20:307-312.
19 +
Lieberman JA, Kane JM, Sarantakos S, Gadaleta D, Woerner M, Alvir J, Ramos-Lorenzi J.  Prediction of relapse in schizophrenia . Arch Gen Psychiatry . 1987;;44:597-603.
20 +
Kirch DG, Jaskiw G, Linnoila M, Wienberger DR, Wyatt RJ.  Plasma amine metabolites before and after withdrawal from neuroleptic treatment in chronic schizophrenic inpatients . Psychiatr Res . 1988;;25:233-242.
21 +
Kopin IJ.  Catecholamine metabolism: basic aspects and clinical significane . Pharmacol Rev . 1985;;37:333-364.
22 +
Curet O, Dennis T, Scatton B.  The formation of deaminated metabolites of dopamine in the locus coeruleus depends upon noradrenergic activity . Brain Res . 1985;;335:297-301.
23 +
Favre R de Haut M, Dalmaz JM, Pequignot JM, Peyrin L.  Peripheral distribution of free dopamine and its metabolites in the rat . J Neural Transm . 1986;;66:135-149.
24 +
Potter WZ, Hsiao JK, Goldman SM.  Effects of renal clearance on plasma concentrations of homovanillic acid: methodologic cautions . Arch Gen Psychiatry . 1989;;46:558-564.

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