, Volume 185, Issue 3, pp 339–347 | Cite as

The effects of escitalopram on working memory and brain activity in healthy adults during performance of the n-back task

  • Emma J. Rose
  • Enrico Simonotto
  • Edgar P. Spencer
  • Klaus P. EbmeierEmail author
Original Investigation



Psychotropic medication affects cognition and brain function, making it a potential confounder in functional neuroimaging studies of psychiatric patients.


To determine whether the sub-acute administration of an antidepressant (escitalopram) would induce differences in cognitive performance and associated brain function, which could be observed within the normal power of a functional imaging study.

Materials and methods

Healthy adults (N=10) received a short course of escitalopram (10 mg/day for 7 days). Participants performed a parametric working memory (WM) task during BOLD fMRI, both while medication-free and after medication. To control for order effects, the medication-free examination was completed by half the subjects before starting medication and by the other half at least one week after medication.


Escitalopram had no significant effect on WM accuracy or reaction time. Preliminary analysis of the imaging data revealed no significant (p corrected<0.05) differences in memory-load-dependent activation between conditions. However, small volume correction analysis of regions that were significant prior to correction for multiple comparisons highlighted between condition differences in regions likely to be susceptible to antidepressant effects (i.e. thalamus, anterior cingulate and inferior frontal gyrus).


These results suggest that the sub-acute administration of antidepressants in healthy controls does not affect cognitive or hemodynamic function in healthy adults to a magnitude greater than one standard deviation unit. Therefore, the confounding effect of antidepressants on signal intensity in imaging studies of medicated, depressed individuals may be limited.


Escitalopram Working memory Major depression Functional MRI 



This work was funded in part by a research studentship from the Medical Research Council (EJR), by a SHEFC Research Development Grant (KPE) and funds from the Gordon Small Charitable Trust (KPE). None of the authors declares an interest that may bias the results presented.


  1. Amado-Boccara I, Gougoulis N, Littre MFP, Galinowski A, Loo H (1995) Effects of antidepressants on cognitive functions: a review. Neurosci Biobehav Rev 19:479–493CrossRefPubMedGoogle Scholar
  2. Beck AT, Ward CH, Mendelson M, Mock J, Erbaugh J (1961) An inventory for measuring depression. Arch Gen Psychiatry 4:53–63Google Scholar
  3. Boyer WF, Feighner JP (1992) An Overview of Paroxetine. J Clin Psychiatry 53:3–6Google Scholar
  4. Burghardt NS, Sullivan GM, McEwen BS, Gorman JM, LeDoux JE (2004) The selective serotonin reuptake inhibitor citalopram increases fear after acute treatment but reduces fear with chronic treatment: a comparison with tianeptine. Biol Psychiatry 55:1171–1178CrossRefPubMedGoogle Scholar
  5. Callicott JH, Mattay VS, Bertolino A, Finn K, Coppola R, Frank JA, Goldberg TE, Weinberger DR (1999) Physiological characteristics of capacity constraints in working memory as revealed by functional MRI. Cereb Cortex 9:20–26CrossRefPubMedGoogle Scholar
  6. Casey BJ, Cohen JD, O’Craven K, Davidson RJ, Irwin W, Nelson CA, Noll DC, Hu XP, Lowe MJ, Rosen BR, Truwitt CL, Turski P (1998) Reproducibility of fMRI results across four institutions using a spatial working memory task. NeuroImage 8:249–261CrossRefPubMedGoogle Scholar
  7. Davidson RJ, Irwin W, Anderle MJ, Kalin NH (2003) The neural substrates of affective processing in depressed patients treated with venlafaxine. Am J Psychiatry 160:64–75CrossRefPubMedGoogle Scholar
  8. Davies J, Lloyd KR, Jones IK, Barnes A, Pilowsky LS (2003) Changes in regional cerebral blood flow with venlafaxine in the treatment of major depression. Am J Psychiatry 160:374–376CrossRefPubMedGoogle Scholar
  9. Del Ben CM, Deakin JFW, Mckie S, Delvai NA, Williams SR, Elliott R, Dolan M, Anderson IM (2005) The effect of citalopram pretreatment on neuronal responses to neuropsychological tasks in normal volunteers: An fMRI study. Neuropsychopharmacology 30:1724–1734CrossRefPubMedGoogle Scholar
  10. Drevets WC, Bogers W, Raichle ME (2002) Functional anatomical correlates of antidepressant drug treatment assessed using PET measures of regional glucose metabolism. Eur Neuropsychopharmacol 12:527–544CrossRefPubMedGoogle Scholar
  11. Fairweather DB, Ashford J, Hindmarch I (1996) Effects of fluvoxamine and dothiepin on psychomotor abilities in healthy volunteers. Pharmacol Biochem Behav 53:265–269CrossRefPubMedGoogle Scholar
  12. Fairweather DB, DalPozzo C, Kerr JS, Lafferty SV, Hindmarch I (1997) Citalopram compared to dothiepin and placebo: effects on cognitive function and psychomotor performance. Hum Psychopharmacol 12:119–126CrossRefGoogle Scholar
  13. Geday J, Hermansen F, Rosenberg R, Smith DF (2005) Serotonin modulation of cerebral blood flow measured with positron emission tomography (PET) in humans. Synapse 55:224–229CrossRefPubMedGoogle Scholar
  14. Gevins A, Cutillo B (1993) Spatiotemporal dynamics of component processes in human working memory. Electroencephalogr Clin Neurophysiol 87:128–143CrossRefPubMedGoogle Scholar
  15. Goldstein BJ, Goodnick PJ (1998) Selective serotonin reuptake inhibitors in the treatment of affective disorders-III. Tolerability, safety and pharmacoeconomics. J Psychopharmacol 12:S55–S87PubMedGoogle Scholar
  16. Gorman JM, Liebowitz MR, Fyer AJ, Goetz D, Campeas RB, Fyer MR, Davies SO, Klein DF (1987) An open trial of fluoxetine in the treatment of panic attacks. J Clin Psychopharmacol 7:329–332PubMedGoogle Scholar
  17. Guilmette TJ, Dabrowski J, Kennedy ML, Gnys J (1999) A comparison of nine WAIS-R short forms in individuals with mild to severe traumatic brain injury. Assessment 6:33–41PubMedGoogle Scholar
  18. Harmer CJ, Bhagwager Z, Cowen PJ, Goodwin GM (2002) Acute administration of citalopram facilitates memory consolidation in healthy volunteers. Psychopharmacology 163:106–110CrossRefPubMedGoogle Scholar
  19. Harmer CJ, Shelley NC, Cowen PJ, Goodwin GM (2004) Increased positive versus negative affective perception and memory in healthy volunteers following selective serotonin and norepinephrine reuptake inhibition. Am J Psychiatry 161:1256–1263CrossRefPubMedGoogle Scholar
  20. Hasbroucq T, Rihet P, Blin O, Possamai CA (1997) Serotonin and human information processing: fluvoxamine can improve reaction time performance. Neurosci Lett 229:204–208CrossRefPubMedGoogle Scholar
  21. Hindmarch I (1988) A pharmacological profile of fluoxetine and other antidepressants on aspects of skilled performance and car handling ability. Br J Psychiatry 153:99–104Google Scholar
  22. Hindmarch I, Bhatti JZ (1988) Psychopharmacological effects of sertraline in normal, healthy volunteers. Eur J Clin Pharmacol 35:221–223CrossRefPubMedGoogle Scholar
  23. Hindmarch I (1995) The behavioral toxicity of the selective serotonin reuptake inhibitors. Int Clin Psychopharmacol 9:13–17PubMedGoogle Scholar
  24. Hindmarch I, Harrison C (1988) The effects of paroxetine and other antidepressants in combination with alcohol in psychomotor activity related to car driving. Hum Psychopharmacol 3(1):13–20CrossRefGoogle Scholar
  25. Hindmarch I, Kerr JS (1994) Effects of paroxetine on cognitive function in depressed patients, volunteers, and elderly volunteers. Med Sci Res 22:669–670Google Scholar
  26. Jansma JM, Ramsey NF, Coppola R, Kahn RS (2000) Specific versus nonspecific brain activity in a parametric n-back task. NeuroImage 12:688–697CrossRefPubMedGoogle Scholar
  27. Kalin NH, Davidson RJ, Irwin W, Warner G, Orendi JL, Sutton SK, Mock BJ, Sorenson JA, Lowe M, Turski PA (1997) Functional magnetic resonance imaging studies of emotional processing in normal and depressed patients: effects of venlafaxine. J Clin Psychiatry 58:32–39Google Scholar
  28. Kennedy SH, Evans KR, Kruger S, Mayberg HS, Meyer JH, McCann S, Arifuzzman AI, Houle S, Vaccarino FJ (2001) Changes in regional brain glucose metabolism measured with positron emission tomography after paroxetine treatment of major depression. Am J Psychiatry 158:899–905PubMedGoogle Scholar
  29. Lancaster JL, Summerlin JL, Rainey L, Freitas CS, Fox PT (1997) The Talairach Daemon: a database server for the Talairach atlas labels. NeuroImage 5:S633Google Scholar
  30. Lancaster JL, Woldorff MG, Parsons LM, Liotti M, Freitas ES, Rainey L, Kochunov PV, Nickerson D, Mikiten SA, Fox PT (2000) Automated Talairach Atlas labels for functional brain mapping. Hum Brain Mapp 10:120–131CrossRefPubMedGoogle Scholar
  31. Loubinoux I, Tombari D, Pariente J, Gerdelat-Mas A, Franceries X, Cassol E, Rascol O, Pastor J, Chollet F (2005) Modulation of behavior and cortical motor activity in healthy subjects by a chronic administration of a serotonin enhancer. NeuroImage 27:299–313CrossRefPubMedGoogle Scholar
  32. Mackay C, Cox T, Burrows B, Lazzerini T (1978) An inventory for the measurement of self reported stress and arousal. Br J Soc Clin Psychol 17:283–284PubMedGoogle Scholar
  33. Masand PS, Gupta S (1999) Selective serotonin-reuptake inhibitors: an update. Harv Rev Psychiatr 7:69–84CrossRefGoogle Scholar
  34. Mayberg HS, Brannan SK, Tekell JL, Silva JA, Mahurin RK, McGinnis S, Jerabek PA (2000) Regional metabolic effects of fluoxetine in major depression: serial changes and relationship to clinical response. Biol Psychiatry 48:830–843CrossRefPubMedGoogle Scholar
  35. Mckie S, Del Ben C, Elliott R, Williams S, Vai N, Anderson I, Deakin J (2005) Neuronal effects of acute citalopram detected by pharmacoMRI. Psychopharmacology 180:680–686CrossRefPubMedGoogle Scholar
  36. Nathan PJ, Sitaram C, Stough C, Silberstein RB, Sali A (2000a) 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 11:639–642PubMedGoogle Scholar
  37. Nathan PJ, Stough C, Siteram G (2000b) Serotonin and information processing: a pharmacodynamic study on the effects of citalopram on cognitive and psychomotor function. Hum Psychopharmacol 15:306–307CrossRefPubMedGoogle Scholar
  38. Nelson HE, Willison J (1991) National Adult Reading Test (NART): test manual. NFER-Nelson, WindsorGoogle Scholar
  39. Nystrom LE, Braver TS, Sabb FW, Delgado MR, Noll DC, Cohen JD (2000) Working memory for letters, shapes, and locations: fMRI evidence against stimulus-based regional organization in human prefrontal cortex. NeuroImage 11:424–446CrossRefPubMedGoogle Scholar
  40. Rey A (1964) L’examen de clinique en psychologie. Presses Universitaires de France, ParisGoogle Scholar
  41. Robertson IH, Ward T, Ridgeway V, Nimmo-Smith I (1994) The test of everyday attention: test manual. Thames Valley Test Company, Bury St. EdmundsGoogle Scholar
  42. Rose EJ, Ebmeier KP (2006) Pattern of impaired working memory during major depression. J Affect Disord (Dec 15, 2005; E-pub ahead of print)Google Scholar
  43. Rose EJ, Simonotto E, Ebmeier KP (2006) Limbic over-activity in depression during preserved performance on the n-back task. NeuroImage 29:203–215PubMedGoogle Scholar
  44. Saxena S, Brody AL, Ho ML, Zohrabi N, Maidment KM, Baxter LR Jr (2003) Differential brain metabolic predictors of response to paroxetine in obsessive-compulsive disorder versus major depression. Am J Psychiatry 160:522–532CrossRefPubMedGoogle Scholar
  45. Shaywitz SE, Shaywitz BA (2005) Dyslexia (specific reading disability). Biol Psychiatry 57:1301–1309CrossRefPubMedGoogle Scholar
  46. Talairach J, Tournoux P (1988) Co-planar stereotaxic atlas of the human brain. Thieme, New YorkGoogle Scholar
  47. Walker LG (1990) The measurement of anxiety. Postgrad Med J 66:S11–S17Google Scholar
  48. Wechsler D (1981) Manual for the Wechsler adult intelligence scale - revised. The Psychological Corporation, San Antonio, TXGoogle Scholar

Copyright information

© Springer-Verlag 2006

Authors and Affiliations

  • Emma J. Rose
    • 1
    • 2
    • 3
  • Enrico Simonotto
    • 1
    • 2
  • Edgar P. Spencer
    • 4
  • Klaus P. Ebmeier
    • 1
    • 2
    Email author
  1. 1.Department of PsychiatryUniversity of EdinburghEdinburghUK
  2. 2.SHEFC Brain Imaging Research Centre for Scotland, Department of Clinical NeurosciencesWestern General HospitalEdinburghUK
  3. 3.Intramural Research ProgrammeNational Institute on Drug AbuseBaltimoreUSA
  4. 4.Medical Toxicology UnitGuys’ and Saint Thomas’ HospitalLondonUK

Personalised recommendations