The selective serotonin re-uptake inhibitors (SSRIs) are increasingly being used to treat depression and anxiety disorders. Gastrointestinal (GI) symptoms are the main side effects, probably resulting from the stimulation of central or peripheral 5-HT receptors. The present double-blind, placebo-controlled study was undertaken to see if the GI side effects of fluvoxamine could be attenuated by the co-administration of the 5-HT3 antagonist ondansetron. The results demonstrate that, in volunteers, a single 100 mg oral dose of fluvoxamine can produce GI symptoms. Co-administration of ondansetron significantly reduced peak nausea and GI side effects, compared with placebo.
Andrews P L R, Bhandari P. (1993) The 5-hydroxytryptamine receptor antagonists as antiemetics: preclinical evaluation and mechanism of action. Eur J Cancer29A (suppl. I): S11-S16
2.
Andrews P L R, Davidson H.M. (1990) Activation of vagal afferent terminals by 5 hydroxytryptamine is mediated by the 5HT3 receptor in the anaesthetised ferret. J Physiol422: 92P
3.
Bergeron R., Blier P. (1994) Cisapride for the treatment of nausea produced by selective serotonin reuptake inhibitors. Am J Psychiatr151: 1084-1086
4.
Black D.W., Wesner R., Bowers W., Gabel J. (1993) A comparison of fluvoxamine, cognitive therapy, and placebo in the treatment of panic disorder. Arch Gen Psychiatr50: 44-50
5.
Butcher M.E. (1993) Global experience with ondansetron and future potential . Oncology50: 191-197
6.
Celada P., Dolera M., Alvarez E., Artigas F. (1992) Effects of acute and chronic treatment with fluvoxamine on extracellular and platelet serotonin in the blood of major depressive patients . Relationship to clinical improvement. J Affective Disord25: 243-250
7.
Del Favero A., Roila F., Basurto C., Minotti V., Ballatori E., Patoia L., Tonato M., Tognoni G. (1990) Assessment of nausea. Eur J Clin Pharmacol38: 115-120
8.
Furman B.L. and Waton N.G. (1989) 5HT and peripheral secretory mechanisms. In Fozard J R (ed.), The peripheral actions of 5HT. Oxford University Press, Oxford, pp. 274-300
9.
Gershon M.D., Mawe G.M., Branchek T.A. (1989) 5HT and enteric neurones. In Fozard J R (ed.), The peripheral actions of 5HT. Oxford University Press, Oxford , pp. 247-273
10.
Gillis C.N. (1985) Peripheral metabolism of serotonin. In Vanhoutte P (ed.), Serotonin and the cardiovascular system. Raven Press, NY, pp. 27-36
11.
Gorard D.A., Libby G.W., Farthing M J G (1994) 5HT and human small intestinal motility: effect of inhibiting 5HT reuptake. Gut35: 496-500
12.
Laporte A.M., Kidd E.J., Vergé D., Gozlan H., Hamon M. (1992) Autoradiographic mapping of central 5HT3 receptors. In Hamon M (ed.), Central and peripheral 5HT3 receptors. Academic Press Ltd, London, pp. 157-187
13.
Legay C., Faudon M., Hery F., Ternaux J.P. (1983) 5HT metabolism in the intestinal wall of the rat. I. The mucosa. Neurochem Int5: 721-727
14.
Martin A.J., Tebbs V.M., Ashford J.J. (1987) Affective disorders in general practice. Treatment of 6000 patients with fluvoxamine. Pharmatherapeutica5: 40-49
15.
Miner W.D., Sanger G.J. (1986) Inhibition of cisplatin-induced vomiting by selective 5-hydroxytryptamine M-receptor antagonism. Br J Pharmacol88: 487-489
16.
Morrow G.R. (1984) The assessment of nausea and vomiting: past problems, current issues and suggestions for future research. Cancer53 (suppl.): 2267-2280
17.
Ortiz J., Artigas F. (1992) Effects of monoamine uptake inhibitors on extracellular and platelet 5HT in rat blood: different effects of clomipramine and fluoxetine . Br J Pharmacol105: 941-946
Pritchard J.F., Bryson J.C., Kernodle A.E., Benedetti T.L., Powell J.R. (1990) Influence of age and gender on the pharmacokinetics of ondansetron. Clin Pharmacol Ther47: 161
20.
Richelson E., Nelson A. (1984) Antagonism by antidepressants of neurotransmitter receptors of normal human brain in vitro. J Pharmacol Exp Ther230: 94-102
21.
Sanger G.J. (1992) The involvement of 5HT3 receptors in visceral function. In Hamon M (ed.), Central and peripheral 5HT3 receptors. Academic Press Ltd, London, pp. 207-255
22.
Schwörer H., Racké K., Kilbinger H. (1987) Spontaneous release of endogenous 5HT and 5HIAA from the isolated vascularly perfused ileum of the guinea pig. Neuroscience21: 297-303
23.
Van Harten J., Van Bemmel P., Dobrinska M.R., Ferguson R.K., Raghoebar M. (1991) Bioavailability of fluvoxamine given with and without food. Biopharm Drug Disposition12: 571-576
24.
de Vries M.H., van Harten J., van Bemmel P., Raghoebar M. (1993) Pharmacokinetics of fluvoxamine maleate after increasing single oral doses in healthy subjects. Biopharm Drug Disposition14: 291-296
25.
Wagner W., Plekkenpol B., Gray T.E. (1992) Review of fluvoxamine safety database. Drugs43: 48-54
26.
Wilde M.I., Plosker G.L., Benfield P. (1993) Fluvoxamine: an updated review of its pharmacology and therapeutic use in depressive illness. Drugs46: 895-924
