Comparison of the antidepressants reboxetine, fluvoxamine and amitriptyline upon spontaneous pupillary fluctuations in healthy human volunteers.
BACKGROUND
Spontaneous fluctuations in the size of the pupil in darkness are 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 serotonin reuptake inhibitor, and amitriptyline (100 mg), a tricyclic antidepressant of known sedative property, upon spontaneous pupillary fluctuations in healthy male volunteers (n=16).


METHODS
Using the recently developed pupillographic sleepiness test (PST), resting pupil diameter was recorded and two measures of pupillary fluctuations were obtained: total power obtained from 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", "anxiety" and "contentedness".


RESULTS
Resting pupil diameter was enhanced by reboxetine, but remained unaffected by the other two antidepressants. Amitriptyline, consistent with its sedative property, increased the total power of pupillary fluctuations and showed a tendency to increase PUI. These pupillary 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 "anxiety".


CONCLUSIONS
The mydriatic effect of reboxetine may be due to noradrenaline reuptake blockade in the iris and/or in the central nervous system. The enhancement of pupillary fatigue waves by the sedative antidepressant amitriptyline, but not by the non-sedative antidepressants fluvoxamine and reboxetine, indicates that the PST is a suitable quantitative objective test for the detection of drug-induced changes in the level of arousal.
Phillips
M A
MA
Division of Psychiatry, University of Nottingham, Queen's Medical Centre, UK.
Bitsios
P
P
Szabadi
E
E
Bradshaw
C M
CM
D000328:Adult; D000639:Amitriptyline / Q000494:pharmacology; D000704:Analysis of Variance; D000928:Antidepressive Agents / Q000494:pharmacology*; D001007:Anxiety; D018592:Cross-Over Studies; D004311:Double-Blind Method; D016666:Fluvoxamine / Q000494:pharmacology; D006240:Happiness; D006801:Humans; D008297:Male; D009025:Morpholines / Q000494:pharmacology; D011569:Psychiatric Status Rating Scales; D011680:Pupil / Q000187:drug effects* / Q000502:physiology; D000077593:Reboxetine; D014851:Wakefulness / Q000187:drug effects
D000928:Antidepressive Agents; D009025:Morpholines; D000639:Amitriptyline; D000077593:Reboxetine; D016666:Fluvoxamine