Skip to main content
NCBI home page
British Journal of Clinical Pharmacology logoLink to British Journal of Clinical Pharmacology
. 1983;15(Suppl 3):385S–392S. doi: 10.1111/j.1365-2125.1983.tb02129.x

A double-blind placebo controlled study to compare the autonomic effects of fluvoxamine with those of amitriptyline and doxepin in healthy volunteers

W H Wilson, H Higano, Y Papadatos, S Kelwala, T A Ban
PMCID: PMC1427650  PMID: 6407500

Abstract

1 A double-blind placebo- and standard-controlled study was designed to determine the autonomic effects of fluvoxamine, a putative antidepressant possessing a high 5-hydroxytryptamine (5-HT) re-uptake-blocking activity with essentially no effects on noradrenaline. The study employed single doses of fluvoxamine (50 mg, 75 mg and 100 mg), amitriptyline (50 mg and 75 mg), doxepin (50 mg and 75 mg) and placebo, each of which was administered to 17 healthy volunteers according to a repeated-measures latin square design balanced for drug carry-over.

2 Both amitriptyline (Ami) and doxepin (Dox) produced statistically significant decreases in salivary flow relative to placebo, and these effects were still present 24 h after taking medication. For none of the doses of fluvoxamine (Flu) tested did the differences from placebo (Plac) approach significance. There were no differences between the mean response to Ami and Dox, and equivalent dose levels produced similar profiles of differences from Plac.

3 Both Ami and Dox produced significant decreases in pupil diameter relative to Plac. Corresponding doses of Ami and Dox produce remarkably similar effects on pupil diameter and the differences from Plac in mean responses were virtually identical. There was a suggestion that higher doses of Flu (75 mg and 100 mg) may produce increases in pupil diameter; however, the effect was not present unless adjustments (covariance analysis) were made for baseline values, and the mean response over the three doses was not different from Plac.

4 Although there was a tendency toward reduced palpebral fissure size, with the effects of Ami and Dox being greater than Flu, there were no reliable, significant differences in this measure.

5 Fluvoxamine neither produced significant changes in pulse rate, systolic and diastolic blood pressure or mean arterial pressure, nor were there effects in those parameters as a function of postural change. In contrast, Dox produced decreases in systolic and diastolic blood pressures. Neither Ami nor Dox produced significant effects on systolic, diastolic or mean arterial blood pressure related to postural change, but three subjects complained of symptoms compatible with orthostatic hypotension after Dox 75 mg.

Full text

PDF
385S

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Arnold S. E., Kahn R. J., Faldetta L. L., Laing R. A., McNair D. M. Tricyclic antidepressants and peripheral anticholinergic activity. Psychopharmacology (Berl) 1981;74(4):325–328. doi: 10.1007/BF00432740. [DOI] [PubMed] [Google Scholar]
  2. Blackwell B. Adverse effects of antidepressant drugs. Part 1: monoamine oxidase inhibitors and tricyclics. Drugs. 1981 Mar;21(3):201–219. doi: 10.2165/00003495-198121030-00002. [DOI] [PubMed] [Google Scholar]
  3. Blackwell B., Stefopoulos A., Enders P., Kuzma R., Adolphe A. Anticholinergic activity of two tricyclic antidepressants. Am J Psychiatry. 1978 Jun;135(6):722–724. doi: 10.1176/ajp.135.6.722. [DOI] [PubMed] [Google Scholar]
  4. Claassen V., Davies J. E., Hertting G., Placheta P. Fluvoxamine, a specific 5-hydroxytryptamine uptake inhibitor. Br J Pharmacol. 1977 Aug;60(4):505–516. doi: 10.1111/j.1476-5381.1977.tb07528.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. DAVIES B. M., GURLAND J. B. Salivary secretion in depressive illness. J Psychosom Res. 1961 Oct;5:269–271. doi: 10.1016/0022-3999(61)90004-6. [DOI] [PubMed] [Google Scholar]
  6. Ghose K., Coppen A., Turner P. Autonomic actions and interactions of mianserin hydrochloride (Org. GB 94) and amitriptyline in patients with depressive illness. Psychopharmacology (Berl) 1976 Sep 17;49(2):201–204. doi: 10.1007/BF00427291. [DOI] [PubMed] [Google Scholar]
  7. JONAS S. Miosis following administration of chlorpromazine and related agents. Am J Psychiatry. 1959 Mar;115(9):817–818. doi: 10.1176/ajp.115.9.817. [DOI] [PubMed] [Google Scholar]
  8. Kerr F. A., Szabadi E. Interaction of desipramine and ciclazindol with adrenergic mechanisms in the human iris [proceedings]. Br J Clin Pharmacol. 1979 Oct;8(4):396P–397P. [PubMed] [Google Scholar]
  9. Kopera H. Anticholinergic and blood pressure effects of mianserin, amitriptyline and placebo. Br J Clin Pharmacol. 1978;5 (Suppl 1):29S–34S. [PMC free article] [PubMed] [Google Scholar]
  10. Mathew R. J., Weinman M., Claghorn J. L. Tricyclic side effects without tricyclics in depression. Psychopharmacol Bull. 1980 Jul;16(3):58–60. [PubMed] [Google Scholar]
  11. Mathew R. J., Weinman M., Claghorn J. L. Xerostomia and sialorrhea in depression. Am J Psychiatry. 1979 Nov;136(11):1476–1477. doi: 10.1176/ajp.136.11.1476. [DOI] [PubMed] [Google Scholar]
  12. Moro F., Scapagnini U., Scaletta S., Drago F. Serotonin nerve endings and regulation of pupillary diameter. Ann Ophthalmol. 1981 Apr;13(4):487–490. [PubMed] [Google Scholar]
  13. Peck A. W., Bye C. E., Clubley M., Henson T., Riddington C. A comparison of bupropion hydrochloride with dexamphetamine and amitriptyline in healthy subjects. Br J Clin Pharmacol. 1979 May;7(5):469–478. doi: 10.1111/j.1365-2125.1979.tb00988.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Peterson G. R., Blackwell B., Hostetler R. M., Kuzma R., Adolphe A. Anticholinergic activity of the tricyclic antidepressants desipramine and doxepin in nondepressed volunteers. Commun Psychopharmacol. 1978;2(2):145–150. [PubMed] [Google Scholar]
  15. Shur E., Checkley S. Pupil studies in depressed patients: an investigation of the mechanism of action of desipramine. Br J Psychiatry. 1982 Feb;140:181–184. doi: 10.1192/bjp.140.2.181. [DOI] [PubMed] [Google Scholar]
  16. Snyder S. H., Yamamura H. I. Antidepressants and the muscarinic acetylcholine receptor. Arch Gen Psychiatry. 1977 Feb;34(2):236–239. doi: 10.1001/archpsyc.1977.01770140126014. [DOI] [PubMed] [Google Scholar]
  17. Szabadi E., Gaszner P., Bradshaw C. M. The peripheral anticholinergic activity of tricyclic antidepressants: comparison of amitriptyline and desipramine in human volunteers. Br J Psychiatry. 1980 Nov;137:433–439. doi: 10.1192/bjp.137.5.433. [DOI] [PubMed] [Google Scholar]
  18. Wilson W. H., Petrie W. M., Ban T. A. Possible lack of anticholinergic effects with mianserin: a pilot study. J Clin Psychiatry. 1980 Feb;41(2):63–65. [PubMed] [Google Scholar]

Articles from British Journal of Clinical Pharmacology are provided here courtesy of British Pharmacological Society

RESOURCES