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

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. 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. 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. 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. 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.