Differential impact of selective serotonin reuptake inhibitors on platelet response to clopidogrel: A randomized, double-blind, crossover trial: A randomized, double-blind, crossover trial

B.H. Rokach, G. Spectre, E. Shai, A. Lotan, A. Ritter, F. Al-Aieshy, R.E. Malmström, D. Varon, R. Alcalai

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10 Scopus citations


Study Objective To assess the effect of two selective serotonin reuptake inhibitors (SSRIs), fluvoxamine and citalopram, that markedly differ in their level of cytochrome P450 (CYP) 2C19 inhibition, on the laboratory response to clopidogrel, a prodrug requiring metabolism by the CYP system, and especially CYP2C19, to produce its active form. Design Randomized, double-blind, crossover trial. Setting Clinical research unit of an academic medical center. Subjects Fifteen healthy male volunteers. Intervention All subjects received clopidogrel as a 300-mg loading dose on day 1, followed by 75 mg/day on days 2 and 3. Platelet function was tested at baseline and then after clopidogrel treatment on day 3. After a washout period of 2 weeks, subjects were randomly assigned in a double-blind manner to receive either citalopram 20 mg/day or fluvoxamine 100 mg/day for 7 days. On day 5, platelet function was tested while receiving the SSRI treatment alone; then, a 300-mg clopidogrel loading dose was administered, followed by clopidogrel 75 mg/day on days 6 and 7. Platelet function was then reassessed on day 7 while receiving the combination of the SSRI and clopidogrel. The treatment protocol was then repeated after a washout period of 2 weeks in all subjects with the other SSRI. Measurements and Main Results The antiplatelet effects of fluvoxamine and citalopram and their interactions with clopidogrel were assessed. The response to these three drugs was assessed by light transmittance aggregometry and vasodilator-stimulated phosphoprotein phosphorylation, reporting P2Y12 receptor reactivity. Both fluvoxamine and citalopram tended to reduce adenosine diphosphate-induced aggregation: 80.8 ± 3.4% at baseline, 67.3 ± 6.3% while receiving citalopram, and 65.8 ± 6.4% while receiving fluvoxamine. All subjects had a good laboratory response to clopidogrel, with a mean aggregation of 23.5 ± 3.2% and a mean platelet reactivity index of 47.7 ± 3.9% (p
Original languageEnglish
Pages (from-to)140-147
Number of pages8
Issue number2
StatePublished - 2015

Bibliographical note

Export Date: 20 July 2022; Cited By: 9; Correspondence Address: R. Alcalai; Heart Institute, Hadassah Hebrew University Medical Center, Ein-Kerem, Jerusalem, 91120, Israel; email: ronny@hadassah.org.il; CODEN: PHPYD


  • Adult
  • Citalopram
  • Cross-Over Studies
  • Cytochrome P-450 CYP2C19
  • Cytochrome P-450 CYP2C19 Inhibitors
  • Double-Blind Method
  • Drug Interactions
  • Fluvoxamine
  • Humans
  • Male
  • Middle Aged
  • Platelet Aggregation Inhibitors
  • Prodrugs
  • Serotonin Uptake Inhibitors
  • Ticlopidine
  • Young Adult
  • adenosine diphosphate
  • citalopram
  • clopidogrel
  • collagen
  • cytochrome P450 2C19
  • fluvoxamine
  • serotonin
  • vasodilator stimulated phosphoprotein
  • antithrombocytic agent
  • CYP2C19 protein, human
  • cytochrome P450 2C19 inhibitor
  • prodrug
  • serotonin uptake inhibitor
  • ticlopidine
  • adult
  • Article
  • controlled study
  • crossover procedure
  • double blind procedure
  • drug determination
  • drug effect
  • drug mechanism
  • drug potentiation
  • drug response
  • enzyme inhibition
  • enzyme mechanism
  • enzyme metabolism
  • flow cytometry
  • human
  • loading drug dose
  • male
  • normal human
  • platelet aggregation assay
  • platelet reactivity
  • protein phosphorylation
  • randomized controlled trial
  • thrombocyte aggregation
  • analogs and derivatives
  • comparative study
  • drug effects
  • drug interaction
  • metabolism
  • middle aged
  • young adult
  • antiplatelets
  • cytochrome P450
  • pharmacodynamics
  • selective serotonin reuptake inhibitors


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