title: Modulation of the critical flicker fusion effects of serotonin reuptake inhibitors by concomitant pupillary changes.
abstract: BACKGROUND
  Serotonin reuptake inhibitors (SSRIs) have been attributed CNS-activating properties based on their ability to elevate the Critical Flicker Fusion (CFF) threshold. However, such an interpretation may be questioned since CFF elevations may also be due to SSRI-induced increases in pupil diameter.
  
  
  OBJECTIVE
  The effect of pupillary changes on CFF assessment following SSRI administration was investigated in a double blind, crossover study.
  
  
  METHODS
  During three periods of 15 days, 21 healthy men and women (30-50 years) received sertraline (50 mg on days 1-8, 100 mg on days 9-15), citalopram (20 mg on days 1-8, 40 mg on days 9-15) and placebo. Assessments were done on days 1, 8 and 15 and consisted of pupillary measurements and CFF assessments with and without pupillary control (a 2-mm artificial pupil) using the Leeds Psychomotor Tester.
  
  
  RESULTS
  Both SSRIs induced an acute and steady increase in pupil diameters. CFF thresholds were depressed following acute administration of sertraline and citalopram, but this was only apparent when a control was made for the pupillary changes. No CFF effects were seen at day 8, but CFF was again reduced at day 15, with and without control for pupil size.
  
  
  CONCLUSIONS
  Mydriasis masked the detrimental effects of both SSRIs on CFF during the acute assessments. Our results raise questions regarding the validity of the assessment of the behavioural toxicity of SSRIs based on CFF measurements without ample control for pupil size, especially when these concern acute measurements.
authors.affiliation: Department of Psychiatry and Neuropsychology, Universiteit Maastricht, Maastricht, The Netherlands. j.schmitt@np.unimaas.nl
authors.forename: Jeroen A J
authors.initials: JA
authors.lastname: Schmitt
authors.forename: Wim J
authors.initials: WJ
authors.lastname: Riedel
authors.forename: Eric F P M
authors.initials: EF
authors.lastname: Vuurman
authors.forename: Monique
authors.initials: M
authors.lastname: Kruizinga
authors.forename: Johannes G
authors.initials: JG
authors.lastname: Ramaekers
mesh_terms: D000328:Adult; D000704:Analysis of Variance; D015283:Citalopram / Q000009:adverse effects / Q000494:pharmacology; D018592:Cross-Over Studies; D004311:Double-Blind Method; D005260:Female; D005425:Flicker Fusion / Q000187:drug effects* / Q000502:physiology; D006801:Humans; D008297:Male; D008875:Middle Aged; D015878:Mydriasis / Q000139:chemically induced; D011680:Pupil / Q000187:drug effects* / Q000502:physiology; D017367:Selective Serotonin Reuptake Inhibitors / Q000009:adverse effects / Q000494:pharmacology*; D020280:Sertraline / Q000009:adverse effects / Q000494:pharmacology
chemical_list: D015283:Citalopram; D017367:Selective Serotonin Reuptake Inhibitors; D020280:Sertraline