Skip to main content
SpringerLink
Log in

Differential effects of escitalopram on attention: a placebo-controlled, double-blind cross-over study

  • Original Investigation
  • Published:
Psychopharmacology Aims and scope Submit manuscript

Abstract

Rationale

The role of serotonin (5-HT) in attention is not fully understood yet.

Objective

We aimed to investigate whether attention is modulated after treatment with escitalopram, a selective serotonin reuptake inhibitor (SSRI).

Methods

We administered 10 mg of escitalopram to 20 healthy subjects in a placebo-controlled, double-blind cross-over design for 1 day or to another 20 participants for a period of 7 days. Attention was assessed at time of plasma peak escitalopram concentration using the computerised Attention Network Test (ANT), which is a combined flanker and cued reaction time task.

Results

The results showed differential effects of serotonergic manipulation on attention depending on sequence of intake. For the acute treatment, we found significant differences between escitalopram and placebo for all warning conditions dependent of sequence of intake: participants receiving escitalopram as first treatment showed significant slower reaction times in all warning conditions as compared with placebo while participants receiving escitalopram as second treatment showed significant faster reaction times as compared with placebo. For the sub-chronic treatment, we found significant differences between escitalopram and placebo depending on sequence of intake, but only for the flanker condition: participants receiving escitalopram first had significant slower reaction times in incongruent trials with escitalopram as compared with placebo while participants starting with placebo had significant shorter reaction times in incongruent trials with escitalopram.

Conclusions

Thus, the results showed a differential effect of escitalopram in cognition, especially in attention, and are discussed with regard to an interaction between serotonin and familiarity with the attention test.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4

Similar content being viewed by others

References

  • Abrams JK, Johnson PL, Hay-Schmidt A, Mikkelsen JD, Shekhar A, Lowry CA (2005) Serotonergic systems associated with arousal and vigilance behaviors following administration of anxiogenic drugs. Neuroscience 133(4):983–97

    Article  CAS  PubMed  Google Scholar 

  • Aronson S, Delgado P (2004) Escitalopram. Drugs Today 40(2):121–131

    Article  CAS  PubMed  Google Scholar 

  • Balducci C, Nurra M, Pietropoli A, Samanin R, Carli M (2003) Revearsal of visual attention dysfunction after AMPA lesions of the nucleus basalis magnocellularis (NBM) by cholinesterase inhibitor donezepil and by a 5-HT1A receptor antagonist WAY 100635. Psychopharmacology 167:28–36

    CAS  PubMed  Google Scholar 

  • Ballaz SJ, Akil H, Watson SJ (2007) The 5-HT7 receptor: role in novel object discrimination and relation to novelty-seeking behaviour. Neuroscience 149(1):192–202

    Article  CAS  PubMed  Google Scholar 

  • Burke WJ (2002) Escitalopram. Expert Opin Investig Drugs 11(10):1477–1486

    Article  CAS  PubMed  Google Scholar 

  • Burke WJ, Gergel I, Bose A (2002) Fixed-dose trial of the single isomer SSRI escitalopram in depressed patients. J Clin Psychiatry 63:331–336

    CAS  PubMed  Google Scholar 

  • Carli M, Samanin R (1992) Serotonin2 receptor agonists and serotonergic anorectic drugs affect rats’ performance differently in a five choice serial reaction time task. Psychopharmacology 106:228–234

    Article  CAS  PubMed  Google Scholar 

  • Carli M, Samanin R (2000) The 5-HT1A receptor agonist 8-OH-PHAT reduces rats’ accuracy of attentional performance and enhances impulsive responding in a five-choice serial reaction time task: role of presynaptic 5-HT1A receptors. Psychopharmacology 149:259–268

    Article  CAS  PubMed  Google Scholar 

  • Clarke HF, Walker SC, Crofts HS, Dalley JW, Robbins TW, Roberts AC (2005) Prefrontal serotonin depletion affects revearsal learning but not attentional set shifting. J Neurosci 25:532–538

    Article  CAS  PubMed  Google Scholar 

  • Clarke HF, Walker SC, Dallex JW, Robbins TW, Roberts AC (2007) Cognitive inflexibility after prefrontal serotonin depletion is behaviourally and neurochemically specific. Cereb Cortex 17(1):18–27

    Article  CAS  PubMed  Google Scholar 

  • Cohen J (1988) Statistical power analysis for the behavioural sciences, 2nd edn. Lawrence Earlbaum Associates, Hillsdale

    Google Scholar 

  • Eriksen BA, Ericksen CW (1974) Effects of noise letters upon the identification of a target letter in a nonsearch task. Percept Psychophys 16:143–149

    Google Scholar 

  • Fan J, McCandliss BD, Sommer T, Raz A, Posner MI (2002) Testing the efficiency and independence of attentional networks. J Cogn Neurosci 14(3):340–347

    Article  PubMed  Google Scholar 

  • Fan J, McCandliss BD, Fossella J, Flombaum JI, Posner MI (2005) The activation of attentional networks. Neuroimage 26(2):471–479

    Article  PubMed  Google Scholar 

  • Faul F, Erdfelder E, Lang AG, Buchner A (2007) G*Power3: a flexible statistical power analysis program for the social, behavioural, and biomedical sciences. Behav Res Meth 39:175–191

    Google Scholar 

  • Fernandez-Duque D, Posner MI (1997) Relating the mechanisms of orienting and alerting. Neuropsychologia 35(4):477–486

    Article  CAS  PubMed  Google Scholar 

  • Fernandez-Duque D, Posner MI (2001) Brain imaging of attentional networks in normal and pathological states. J Clin Exp Neuropsychol 23:74–93

    Article  CAS  PubMed  Google Scholar 

  • Gray JA (1982) The neuropsychology of anxiety: an inquiry into the functions of the septo-hippcampal system. Clarendon Press, Oxford

    Google Scholar 

  • Gray JA, Smith T (1969) An arousal-decision model for partial reinforcement and discrimination learning. In: Gilbert R, Sutherland N (eds) Animal Discrimination Learning. Academic Press, New York, pp 243–272

    Google Scholar 

  • Hedges LV, Olkin I (1985) Statistical methods for meta-analysis. Academic Press, Orlando

    Google Scholar 

  • Hennig J, Huwe S, Netter P (1997) The antagonism of ipsapirone induced biobehavioral responses by ±pindolol in high and low impulsives. J Neural Transm 104:1027–1035

    Article  CAS  PubMed  Google Scholar 

  • Hennig J, Kroeger A, Meyer B, Prochaska H, Krien P, Huwe S, Netter P (1998) Personality correlates of ±pindolol induced decreases in prolactin. Pharmacopsychiatry 31:19–24

    Article  CAS  PubMed  Google Scholar 

  • Klein N, Sacher J, Geiss-Granadia T, Attarbaschi T, Mossaheb N, Lanzenberger R, Pötzi C, Holik A, Spindelegger C, Asenbaum S, Dudczak R, Tauscher J, Kasper S (2006) In vivo imaging of serotonin transporter occupancy by means of SPECT and [123I]ADAM in healthy subjects administered different doses of escitalopram or Citalopram. Psychpharmacology 188:263–272

    Article  CAS  Google Scholar 

  • Klein N, Sacher J, Geiss-Granadia T, Mossaheb N, Attarbaschi T, Lanzenberger R, Spindelegger C, Holik a, Asenbaum A, Dudczak R, Tauscher J, Kasper S (2007) Higher serotonin transporter occupancy after multiple dose administration of escitalopram compared to citalopram: an [123I]ADAM SPECT study. Psychopharmacology 191:333–339

    Article  CAS  PubMed  Google Scholar 

  • Koskinen T, Ruotsalainen S, Puumala T, Lappalainen R, Koivisto E, Mannisto PT, Sirvio J (2000) Activation of 5-HT2A receptors impairs response control in rats in a five-choice serial reaction time task. Neuropharmacology 39:471–481

    Article  CAS  PubMed  Google Scholar 

  • Lader M, Melhuish A, Fricka G, Fredericson Overo K, Christensen V (1986) The effects of citalopram in single and repeated doses and with alcohol on physiological and psychological measures in healthy subjects. Eur J Clin Pharmacol 31:183–190

    Article  CAS  PubMed  Google Scholar 

  • Meltzer HY (1999) The role serotonin in antipsychotic drug action. Neuropsychopharmacology 21:106S–115S

    CAS  PubMed  Google Scholar 

  • Meltzer HY, LI Z, Kaneda Y, Ichikawa J (2003) Serotonin receptors: their key role in drugs to treat schizophrenia. Prog Neuropsychopharmacol Biol Psychiatry 27(7):1159–72

    Article  CAS  PubMed  Google Scholar 

  • Mirjana C, Baviera M, Invernizzi RW, Balducci C (2004) The serotonin 5-HT2A receptors antagonist M100907 prevents impairment in attentional performance by NMDA receptor blockade in the rat prefrontal cortex. Neuropsychopharmacology 29:1637–1647

    Article  CAS  PubMed  Google Scholar 

  • Mongeau R, Blier P, de Montigy C (1997) The serotonergic and noradrenergic systems of the hippocampus: their interactions and the effects of antidepressant treatments. Brains Res Rev 23(3):145–195

    Article  CAS  Google Scholar 

  • Nathan PJ, Sitaram G, Stough C, Silberstein RB, Sali A (2000) Serotonin, noradrenaline and cognitive function: a preliminary investigation of the acute pharmacodynamic effects of a serotonin versus a serotonin and noradrenaline reuptake inhibitor. Behav Pharmacol 11:639–642

    CAS  PubMed  Google Scholar 

  • Netter P, Hennig J, Rohrmann S (1999) Psychobiological differences between aggression and psychoticism. Pharmacopsychiatry 32:5–12

    Article  CAS  PubMed  Google Scholar 

  • Ogren SO, Eriksson TM, Elvander-Tottie E, D’Addario C, Ekstroem JC, Svenningsson P, Meister B, Kehr J, Stiedl O (2008) The role of 5-HT(1A) receptors in learning and memory. Behav Brain Res. doi:10.1016/j.bbr.2008.02.023

    PubMed  Google Scholar 

  • Rammsayer T, Netter P (1988) Effects of changes in brain 5-HT activity on indicators for cortical arousal. Int Clin Psychopharmacol 3:231–237

    Article  CAS  PubMed  Google Scholar 

  • Riedel WJ, Klaassen T, Deutz NEP, van Someren A, van Praag HM (1999) Tryptophan depletion in normal volunteers produces selective impairment in memory consolidation. Psychopharmacology 141:362–369

    Article  CAS  PubMed  Google Scholar 

  • Riedel WJ, Eikmans K, Heldens A, Schmitt JAJ (2005) Specific serotonergic reuptake inhibition impairs vigilance performance acutely and after subchronic treatment. J Psychopharmacol 19(1):12–20

    Article  CAS  PubMed  Google Scholar 

  • Reis M, Chermá CB, Bengtsson F (2007) Therapeutic drug monitoring of escitalopram in an outpatient setting. Ther Drug Monit 29(6):758–766

    Article  CAS  PubMed  Google Scholar 

  • Robbins TW (1997) Arousal systems and attentional processes. Biol Psychol 45:57–71

    Article  CAS  PubMed  Google Scholar 

  • Robbins TW (2007) Shifting and stopping: fronto-striatal substrates, neurochemical modulation and clinical implications. Phil Trans R Soc B 362:917–932

    Article  CAS  PubMed  Google Scholar 

  • Robbins TW, Roberts AC (2007) Differential regulation of fronto-executive function by the monoamines and acetylcholine. Cereb Cortex 17:i151–i160

    Article  PubMed  Google Scholar 

  • Riedel SJAJ, WJ VEFPM, Kruizinga M, Ramaekers JG (2002) Modulation of the critical flicker fusion effects of serotonin reuptake inhibitors by concomitant papillary changes. Psychopharmacology 160:381–386

    Article  PubMed  Google Scholar 

  • Sogaard B, Mengel H, Rao N, Larsen F (2005) The pharmacokinetics of escitalopram after oral and intravenous administration of single and multiple doses to healthy subjects. J Clin Pharmacol 45(12):1400–1406

    Article  CAS  PubMed  Google Scholar 

  • Stahl SM (2005) Essential psychopharmacology. The prescriber’s guide. University Press, Cambrigde

    Google Scholar 

  • Verheij MMM, VeenflietJV KTG, Steenhof M, Cools AR (2009) Individual differences in the sensitivity to serotonergic drugs: a pharmacobehavioural approach using rats selected on the basis of their response to novelty. Psychopharmacology (Berl) . doi:10.1007/s00213-009-1552-1

    Google Scholar 

  • Waugh J, Goa KL (2003) Escitalopram: a review of its use in the management of major depressive and anxiety disorders. CNS Drugs 17(5):343–362

    Article  CAS  PubMed  Google Scholar 

  • Wingen M, Kuypers KP, Ramaekers JG (2007) The role of 5-HT1A and 5-HT2A receptors in attention and motor control: a mechanistic study in healthy volunteers. Psychpharmacology 190(3):391–400

    Article  CAS  Google Scholar 

  • Yasuno F, Suhara T, Nakayama T, Ichimiya T, Okubo Y, Takano A, Anso T, Inoue M, Maeda J, Suzuki K (2004) Inhibitory effect of hippocampal 5-HT1A receptors on human explicit memory. Am J Psychiatry 161(8):1505–1506

    Article  Google Scholar 

  • Yevtushenko VY, Belous AI, Yevtushenko YG, Gsinin SE, Buzik OJ, Agibalova TV (2007) Efficacy and tolerability of escitalopram versus citalopram in major depressive disorder: a 6-week, multicenter, prospective, randomized, double-blind, active-controlled study in adult outpatients. Clin Ther 29(11):2319–2332

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgements

This study was a research grant supported in part by H. Lundbeck A/S (Copenhagen, Denmark). Lundbeck was not responsible for the creation of the study, the choice of investigators, the control of allocation schedule, the conduct of the trial, the collection and monitoring of data, the analysis and interpretation and the writing of the manuscript. B. Drueke, J. Baetz, M. Boecker and Prof. Dr. S. Gauggel report no other conflicts of interest. Dr. O. Moeller received travel support from Pfizer and Servier. Prof. Dr. C. Hiemke has served as a consultant for Servier (Paris, France) and Pfizer (New York, NY). He has served on the speakers’ bureau of Bristol-Myers Squibb, Janssen Cilag, Otsuka, Pfizer, Astra Zeneca, Sanofi-Aventis (Berlin, Germany), Lundbeck (Copenhagen, Denmark), Servier and Eli Lilly (Indianapolis, IN). He has received grant supports from Sanofi-Aventis and Pfizer. Prof. Dr. G. Gründer has served as a consultant for Astra Zeneca (London, UK), Bristol-Myers Squibb (New York, NY), Johnson & Johnson (Beerse, Belgium), Otsuka (Rockville, MD) and Pfizer (New York, NY). He has served on the speakers’ bureau of Astra Zeneca, Bristol-Myers Squibb, Eli Lilly (Indianapolis, IN), Janssen Cilag, Otsuka, Pfizer, Servier (Paris, France) and Wyeth (Madison, NJ). He has received grant support from Alkermes (Cambridge, Ma), Bristol-Myers Squibb, Eli Lilly, Johnson & Johnson, and Pfizer.

Author information

Authors and Affiliations

  1. Department of Medical Psychology and Medical Sociology, RWTH Aachen University, Pauwelsstr. 30, 52074, Aachen, Germany

    Barbara Drueke, Julia Baetz, Maren Boecker & Siegfried Gauggel

  2. Department of Psychiatry and Psychotherapy and JARA - Translational Brain Medicine, RWTH Aachen University, Pauwelsstr. 30, 52074, Aachen, Germany

    Olaf Moeller & Gerd Gründer

  3. Department of Psychiatry and Psychotherapy, University of Mainz, Untere Zahlbacher Str. 8, 55131, Mainz, Germany

    Christoph Hiemke

Authors
  1. Barbara Drueke
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Julia Baetz
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Maren Boecker
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Olaf Moeller
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Christoph Hiemke
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Gerd Gründer
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Siegfried Gauggel
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Barbara Drueke.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Drueke, B., Baetz, J., Boecker, M. et al. Differential effects of escitalopram on attention: a placebo-controlled, double-blind cross-over study. Psychopharmacology 207, 213–223 (2009). https://doi.org/10.1007/s00213-009-1649-6

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00213-009-1649-6

Keywords

Search

Navigation