We investigated the relationships between the changes in plasma catecholamine metabolites
obtained from depressed patients before and after administration of sulpiride, a benzamide
compound, or fluvoxamine, a selective serotonin reuptake inhibitor (SSRI), and between
clinical responses to treatment with each of these drugs. Responders to sulpiride
had significantly lower plasma homovanillic acid (pHVA) levels before administration
of sulpiride than did non-responders or controls (responders: 4.5 ± 3.1 ng/ml, non-responders:
11.1 ± 5.9 ng/ml, controls: 10.9 ± 5.3 ng/ml). Positive relationships were observed
between changes in pHVA levels and improvement rates in the 17-item Hamilton Depression
Rating Scale (Ham-D). In contrast, responders to fluvoxamine had significantly higher
plasma free 3-methoxy-4-hydroxyphenylglycol (pMHPG) levels before administration of
fluvoxamine than did non-responders or controls (responders: 8.5 ± 1.8 ng/ml, non-responders:
5.9 ± 2.I ng/ml, controls: 5.2 ± 2.9 ng/ml). Negative relationships were observed
between changes in pMHPG levels and improvement rates in Ham-D. These results suggest
that lower pretreatment pHVA levels and higher pretreatment levels of pMHPG might
be predictors of response to sulpiride and fluvoxamine, respectively, and that sulpiride
might produce a functional increase in the dopaminergic system, resulting in improvement
in some depressive symptoms; fluvoxamine, on the other hand, might produce a functional
decrease in the noradrenergic system via serotonergic neurons, resulting in improvement of those symptoms.
References
- 1
Aberg-Wistedt A, Ross S B, Jaostell K G, Sjoquist B.
A double-blind study of zimelidine, a serotonin uptake inhibitor, and desipramine,
a noradrenaline uptake inhbitor, in endogenous depression.
Acta Psychiatr Scand.
1982;
66
66-82
- 2
Asnis G M, Hameedi F A, Goggard A W, Potkin S G, Black D, Jameel M, Desagani K, Woods S W.
Fluvoxamine in the treatment of panic disorder: a multi-center, double-blind, placebo-controlled
study in outpatients.
Psychiatry Res.
2001;
103
1-14
- 3
Banki C M.
Correlation between cerebrospinal fluid amine metabolites and psychomotor activity
in affective disorders.
J Neurochem.
1977;
28
255-257
- 4
Benfield P, Ward A.
Fluvoxamine: a review of its pharmacodynamic and pharmacokinetic properties, and therapeutic
efficacy in depressive illness.
Drugs.
1986;
32
313-334
- 5
Bocchetta A, Bernardi F, Burrai C, Pedditzi M, Del Zompo M.
A double-blind study of L-sulpiride versus amitriptyline in lithium maintained bipolar
depressives.
Acta Psychiatr Scand.
1993;
88
434-439
- 6
Cassano G B, Musetti L, Soriani A, Savino M.
The pharmacologic treatment of depression: drug selection criteria.
Pharmacopsychiatry.
1993;
26 (suppl 1)
17-23
- 7
Checkley S.
Monoamines, depression and antidepressant drugs.
Pharmacopsychiatry.
1988;
21
6-8
- 8
Coplan J D, Papp L A, Pine D, Martinez J, Cooper T, Rosenblum L A. et al .
Clinical improvement with fluoxetine therapy and noradrenergic function in patients
with panic disorder.
Arch Gen Psychiatry.
1997;
54
643-648
- 9
De Bellis M D, Geracioti T D, Altemus M, Kling M A.
Cerebrospinal fluid monoamine metabolites in fluoxetine-treated patients with major
depression and in healthy volunteers.
Biol Psychiatry.
1993;
33
636-641
- 10
Grant M M, Weiss J M.
Effects of chronic antidepressant drug administration and electroconvulsive shock
on locus coeruleus electrophysiologic activity.
Biol Psychiatry.
2001;
49
117-129
- 11
Grossmann F, Potter W Z.
Catecholamines in depression: a cumulative study of urinary norepinephrine and its
major metabolites in unipolar and bipolar depressed patients versus healthy volunteers
at the NIMH.
Psychiatry Res.
1999;
30
21-27
- 12
Hall H, Sä Llemark M, Wedel I.
Acute effects of atypical antidepressants on various receptors in the rat brain.
Acta Pharmacol Et Toxicol.
1984;
54
379-384
- 13
Hochberg H M, Kanter D, Houser V P.
Electrocardiographic findings during extended clinical trials of fluvoxamine in depression:
one years experience.
Pharmacopsychiatry.
1995;
28
253-256
- 14
Hudson J I, McElroy S L, Raymond N C, Crow S, Keck PE J r, Carter W P, Mitchell J E,
Strakowski S M, Pope HG J r, Coleman B S, Jonas J M.
Fluvoxamine in the treatment of binge-eating disorder: a multicenter placebo-controlled,
double-blind trial.
Am J Psychiatry.
1998;
155
1756-1762
- 15 Jenner P, Marsden C D. The mode of action of sulpiride as an atypical antidepressant
agent. In: Costa E, Racagni G (eds)
Typical and atypical antidepressants: Clinical practice. Raven Press New York; 1982: 85-103
- 16 Jimerson D C. Role of dopamine mechanisms in the affective disorders. In: Meltzer
HY (ed)
Psychopharmacology 3rd generation. Raven Press New York; 1987: 505-511
- 17
Karege F, Bovier P, Hilleret H, Guillard J M.
Lack of effect of anxiety on total plasma MHPG in depressed patients.
J Affect Disord.
1993;
28
211-217
- 18
Ko H C, Lu R B, Shiah I S, Hwang C C.
Plasma free 3-methoxy-4-hydroxyphenylglycol predicts response to fluoxetine.
Biol Psychiatry.
1997;
41
774-781
- 19
Kopin I J.
Catecholamine metabolism: basic aspects and clinical significance.
Pharmacol Rev.
1985;
37
333-364
- 20
Korf J, Van Praag H M.
Retarded depression and the dopamine metabolism.
Psychopharmacologia.
1971;
19
199-203
- 21
Markianos M, Botsis A, Arvantis Y.
Biogenic amine metabolites in plasma of drug-naive schizophrenic patients: association
with symptomatology.
Biol Psychiatry.
1992;
32
288-292
- 22
Maas J W, Hattox S E, Greene N M, Landis D H.
3-Methoxy-4-hydroxyphenethyleneglycol production by human brain in vivo.
Science.
1979;
205
1025-1027
- 23
Maas J W, Koslow S H, Katz M M, Bowden C L, Gibbons R L, Stokes P E. et al .
Pretreatment neurotransmitter metabolite levels and response to tricyclic antidepressant
drugs.
Am J Psychiatry.
1984;
141
1159-1171
- 24
Minegishi A, Ishizaki T.
Rapid and simple method for the simultaneous determination of 3,4-dihydroxyphenylacetic
acid, 5-hydroxyindole-3 -acetic acid and 4-hydroxy-3-methoxyphenylacetic acid in human
plasma by high-performance liquid chromatography with electrochemical detection.
J Chromatography.
1984;
308
55-63
- 25
Minegishi A, Ishizaki T.
Determination of free 3-methoxy-4-hydroxyphenylglycol with several other monoamine
metabolites in plasma by high-performance liquid chromatography with amperometric
detection.
J Chromatography.
1984;
311
51-57
- 26
Möller H J.
Are all antidepressants the same?.
J Clin Psychiatry.
2000;
61 (suppl 6)
24-28
- 27
Mundo E, Maina G, Uslenghi C.
Munticentre, double-blind, comparison of fluvoxamine and clomipramine in the treatment
of obsessive-compulsive disorder.
Int Clin Psychopharmacol.
2000;
15
69-76
- 28
Nagaoka S, Iwamoto N, Arai H.
First-episode neuroleptic-free schizophrenics: concentrations of monoamines and their
metabolites in plasma and their correlations with clinical response to haloperidol
treatment.
Biol Psychiatry.
1997;
41
857-864
- 29
Nakamura J, Yoshimura R, Ueda N, Eto S.
Interaction between fluvoxamine and smoking (nicotine), caffeine, and levomepromazine
in Japanese.
Int J Neuropsychopharmacol.
2000;
3 (suppl 1)
s244
- 30
Nakamura J, Yoshimura R, Okuno T, Ueda N, Hachida M, Yasumoto K, Egami H, Maeda H,
Nishi M, Aoyagi S.
Association of plasma free-3-methoxy-4-hydroxy-phenyl (ethylene) glycol, natural killer
cell activity, and delirium in post-operative patients.
Int Clin Psychophramacol.
2000;
16
339-343
- 31
Racagni G, Brunello N.
Physiology to functionality: the brain and neurotransmitter activity.
Int Clin Psychophramacol.
1999;
14 (suppl 1)
s3-7
- 32
Richelson E, Nelson A.
Antagonism by antidepressants of neurotransmitter receptors of normal human brain
in vitro.
J Pharmacol Exp Ther.
1984;
230
94-102
- 33
Roy A, Pickar D, Linnoila M, Doran A R, Ninan P, Paul S M.
Cerebrospinal fluid monoamine and monoamine metabolite concentrations in melancholia.
Psychiatry Res.
1985;
15
281-292
- 34
Rüther E, Degner D, Munzel U, Brunner E, Lenhard G, Biehl J. et al .
Antidepressant action of sulpiride. Results of a placebo-controlled double-blind trial.
Pharmacopsychiatry.
1999;
32
127-135
- 35
Sheline Y, Bardgett M E, Csernansky J G.
Correlated reductions in cerebrospinal fluid 5-HIAA and MHPG concentrations after
treatment with selective serotonin reuptake inhibitors.
J Clin Psychopharmacol.
1997;
17
11-14
- 36 Siever L J. Role of noradrenergic mechanism in the etiology of the affective disorders. In:
Meltzer HY (eds)
Psychophannacology 3rd generation. Raven Press New York; 1987: 493-504
- 37
Standish-Barry H M, Bouras N, Bridges P K, Watson J P.
A randomized double blind group comparative study of sulpiride and amitriptyline in
affective disorder.
Psychopharmacology.
1983;
81
258-260
- 38 Stahl S M. Essential psychopharmacology. Cambridge University Press 2000
- 39
Szabo S T, Blier P.
Effect of combined 5-HT reuptake inhibition and 5-HT2A antagonism on the firing activity of NE neurons.
Soc Neurosci Abstr.
2000;
26
1928
- 40
Szabo S T, de Montigny C, Blier P.
Progressive attenuation of the firing activity of locus coeruleus noradrenergic neurons
by sustained administration of selective serotonin reuptake inhibitors.
Int J Neuropsychopharmacol.
2000;
3
1-11
- 41 The Research Unit on Pediatric Psychopharmacology Anxiety Study Group: Fluvoxamine
for the treatment of anxiety disorders in children and adolescents. N Engl J Med 2001
344: 1279-1285
- 42
Ueda N, Yoshimura R, Nakamura J.
Fluvoxamine might improve some depressive symptoms by indirectly influencing noradrenergic
neurons.
Int J Neuropsychopharmacol.
2000;
3 (suppl 1)
s238
- 43
Ueda N, Yoshimura R, Shinkai K, Nakamura J.
Fluvoxamine-induced nausea.
Psychiatry Res.
2001;
104
259-264
- 44
Van Scheyen J D, Van Praag H M, Korf J.
Controlled study comparing nomifensine and clomipramine in unipolar depression, using
the probenecid technique.
Br J Clin Parmacol.
1977;
4 (suppl 2)
s179-184
- 45
Verbeeck W J, Berk M, Paiker J, Jersky B.
The prolactin response to sulpiride in major depression: the role of the D2 receptor
in depression.
Eur Neuropsychopharmacol.
2001;
11
215-220
- 46
Ware M R.
Fluvoxamine: a review of the controlled trials in depression.
J Clin Psychiatry.
1997;
58 (suppl 5)
s15-23
- 47
Yazici O, Arieioglu F, Gurrit G, Ucok A, Tastaban Y, Ozguroglu M, Durat T, Sahin D.
Noradrenergic and serotoninergic depression.
J Affect Disord.
1993;
27
123-129
- 48
Yoshimura R, Ueda N, Nakamure J.
Low dosage of levomepromazine did not increase plasma concentrations of fluvoxamine.
Int Clin Psychopharmacol.
2000a ;
15
233-235
- 49
Yoshimura R, Nakamura J, Ueda N, Terao T.
Effect of risperidone on plasma free 3-methoxy-4-hydroxyphenylglycol (pMHPG) levels
in schizophrenic patients: relationship among plasma concentrations of risperidone
and 9-hydroxyrisperidone, pMHPG levels, and clinical improvement.
Int Clin Psychopharmacol.
2000b ;
15
175-180
- 50
Yoshimura R, Yamada Y, Ueda N, Nakamura J.
Changes in plasma monoamine metabolites during acute lithium intoxication.
Hum Psychopharmacol.
2000c ;
15
357-360
- 51
Yoshimura R, Kakihara S, Soya A, Ueda N, Shinkai K, Nakamura J.
Effect of clonazepam treatment on antipsychotic drug-induced Meige syndrome and changes
in plasma levels of GABA, HVA, and MHPG during treatment.
Psychiatry Clin Neurosci.
2001;
55
543-546
Nobuhisa Ueda
Department of Psychiatry
School of Medicine
University of Occupational and Environmental Health
1-1 Iseigaoka
Yahatanisi-ku
Kitakyusyu, 807-8555
Fukuoka
Japan
Telefon: +81 (93) 691-7253
Fax: +81 (93) 692-4894
eMail: EZD04735@nifty.com