Comparison of the effects of venlafaxine, paroxetine and desipramine on the pupillary light reflex in man

Rationale: The time-course of the pupillary light reflex response is determ ined by the successive activation of the parasympathetic and sympathetic in nervations of the iris, the latency and the amplitude reflecting parasympat hetic and the recovery time mainly sympathetic activity. Objective. To comp are the effects of single doses of three antidepressants (venlafaxine: sero tonin/noradrenaline reuptake inhibitor, paroxetine: selective serotonin reu ptake inhibitor and desipramine: tricyclic antidepressant) on resting pupil diameter and the pupillary light reflex response. Methods: Fifteen healthy male volunteers participated in five weekly sessions, each of which was as sociated with one treatment (venlafaxine 75 mg or 150 mg, paroxetine 20 mg, desipramine 100 mg, or placebo) according to a double-blind, double-dummy, balanced, cross-over design. An infrared binocular television pupillometer was used for the recording of the resting pupil diameter and the pupillary light reflex in darkness, in previously dark-adapted eyes. Resting pupil d iameter in darkness was recorded before and after treatment. The pupillary light reflex was elicited after treatment, with six light hashes (green, 56 5 nm peak wavelength) of 200 ms duration and of incremental illuminance (me asured in the plane of the cornea): 3.0 x 10(-3), 8.5 x 10(-3) 2.5 x 10(-2) 7.0 x 10(-2) 0.18, 0.43 mW cm(-2). The parameters studied were: latency, a mplitude and 75% recovery time. Results. Analyses of variance followed by p ost hoc tests (least significant difference test or Dunnett's test; P < 0.0 5) revealed that both doses of venlafaxine produced a significant increase in resting pupil diameter, decrease in amplitude and shortening of the 75% recovery time of the light reflex response; venlafaxine 150 mg prolonged th e latency, while the other treatments had no significant effects. Conclusio ns. The increase in resting pupil diameter could be indicative of parasympa thetic inhibition and/or sympathetic activation. The shortening of the reco very time of the light reflex response is consistent with sympathetic poten tiation resulting from noradrenaline uptake blockade in the iris. The prolo ngation of the latency and decrease of the amplitude of the light reflex re sponse are indicative of a parasympatholytic effect of venlafaxine. However , as venlafaxine has negligible affinity for muscarinic cholinoceptors, thi s effect cannot be attributed to the blockade of cholinoceptors in the iris . A possible explanation for this finding is that it reflects a central rat her than a peripheral effect of the drug: the blockade of noradrenaline upt ake in the brain could lead to the potentiation of the noradrenergic inhibi tion of central parasympathetic (Edinger-Westphal) neurones. These results demonstrate the ability of therapeutically relevant single doses of venlafa xine to potentiate noradrenergic responses in man, consistent with the bloc kade of noradrenaline uptake.