Comparison of the antidepressants reboxetine, fluvoxamine and amitriptyline upon spontaneous pupillary fluctuations in healthy human volunteers

Rationale: Spontaneous fluctuations in the size of the pupil in darkness ar e a recognised index of "sleepiness". Objective: To evaluate the effects of single oral doses of three antidepressants: reboxetine (4 mg), a selective noradrenaline reuptake inhibitor, fluvoxamine (100 mg). a selective seroto nin reuptake inhibitor, and amitriptyline (100 mg), a tricyclic antidepress ant of known sedative property, upon spontaneous pupillary fluctuations in healthy male volunteers (n=16). Methods: Using the recently developed pupil lographic sleepiness test (PST), resting pupil diameter was recorded and tw o measures of pupillary fluctuations were obtained: total power obtained fr om a fast Fourier transform and spectral analysis, and the pupillary unrest index (PUI), a cumulative measure of changes in pupil size. Subjects also rated themselves on a battery of visual analogue scales for "alertness", "a nxiety" and "contentedness". Results: Resting pupil diameter was enhanced b y reboxetine, but remained unaffected by the other two antidepressants. Ami triptyline, consistent with its sedative property, increased the total powe r of pupillary fluctuations and showed a tendency to increase PUI. These pu pillary effects of amitriptyline were paralleled by reduced scores on the " alertness", "contentedness" and "anxiety" self ratings. Neither fluvoxamine nor reboxetine affected pupillary fatigue waves or subjective ratings of " alertness". Reboxetine caused a small reduction in subjectively rated "anxi ety". Conclusions: The mydriatic effect of reboxetine may be due to noradre naline reuptake blockade in the iris and/or in the central nervous system. The enhancement of pupillary fatigue waves by the sedative antidepressant a mitriptyline, but not by the non-sedative antidepressants fluvoxamine and r eboxetine, indicates that the PST is a suitable quantitative objective test for the detection of drug-induced changes in the level of arousal.