Skip to main content
Log in

Cognitive performance in depressed patients after chronic use of antidepressants

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

Abstract

Rationale

Depressive disorders are conditions that often require continuous treatment, and it is therefore important to evaluate the consequences of prolonged administration. There are few studies assessing cognitive functions of depressed patients after long-term use of antidepressants.

Objectives

This study evaluated the cognitive performance of depressed patients treated with antidepressants for at least 6 months.

Methods

Patients with major depression (DSM-IV) using imipramine for 2.4±0.6 years (mean±SE), clomipramine for 2.8±1.2 years, fluoxetine for 1.8±0.3 years and sertraline for 1.5±0.3 years were compared to matched controls (sex, age and educational level) without any psychiatric diagnosis. Memory evaluation consisted of episodic, implicit and working memory tests as well as metamemory assessment.

Results

(a) Psychomotor performance of patients taking imipramine was worse than that of controls in inserting pins and a visual reaction time task; on the performance of tapping the difference from controls varied according to dose/weight for patients taking clomipramine and fluoxetine. (b) For memory tests, differences between patients taking sertraline and controls were observed in the number of digits and words recalled; the difference between patients and controls varied according to dose/weight on the number of familiar words correctly completed for patients taking clomipramine and on digit span backward for those taking sertraline. (c) Metamemory was worse in all patient groups irrespective of patients’ clinical state.

Conclusions

The impairment in psychomotor and memory performances associated with these antidepressants seems to be of low intensity and of questionable clinical relevance.

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

Access this article

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

Instant access to the full article PDF.

Similar content being viewed by others

Notes

  1. We expect a variation of 14.7±5.6 for each increase of one unit on the dose/weight covariate. A similar interpretation may be made for fluoxetine.

References

  • Allen D, Curran HV, Lader M (1991) The effects of repeated doses of clomipramine and alprazolam on physiological, psychomotor and cognitive functions in normal subjects. Eur J Clin Pharmacol 40:355–362

    Article  PubMed  CAS  Google Scholar 

  • Amado-Boccara I, Gougoulis N, Poirier Littre MF, Galinowski A, Loo H (1995) Effects of antidepressants on cognitive functions: a review. Neurosci Biobehav Rev 19:479–493

    Article  PubMed  CAS  Google Scholar 

  • Amin MM, Khan P, Lehmann HE (1980) The differential effects of viloxazine and imipramine on performance tests: their relationship to behavioural toxicity. Psychopharmacol Bull 16:57–58

    PubMed  CAS  Google Scholar 

  • APA (1994) Diagnostic and statistical manual of mental disorders, 4th edn. American Psychiatric Association, Washington, DC

    Google Scholar 

  • Bartfai A, Asberg M, Martensson B, Gustavsson P (1991) Memory effects of clomipramine treatment: relationship to CSF monoamine metabolites and drug concentrations in plasma. Biol Psychiatry 30:1075–1092

    Article  PubMed  CAS  Google Scholar 

  • Beck AT, Ward CH, Mendelson M, Mock J, Erbaugh J (1961) An inventory for measuring depression. Arch Gen Psychiatry 4:561–571

    PubMed  CAS  Google Scholar 

  • Beck AT, Steer RA, Garbin MG (1988) Psychometric properties of the Beck Depression Inventory: twenty-five years of evaluation. Clin Psychol Rev 8:7–100

    Article  Google Scholar 

  • Bennett-Levy J, Powell GE (1980) The Subjective Memory Questionnaire (SMQ). An investigation into the self-reporting of ‘real-life’ memory skills. Br J Soc Clin Psychol 19:177–188

    Google Scholar 

  • Biaggio AMB, Natalício L (1979) Manual para o inventário de ansiedade traço-estado (IDATE). Centro Editor de Psicologia Aplicada (CEPA), Rio de Janeiro

  • Bond AJ, Lader MH (1972) Residual effects of hypnotics. Psychopharmacologia 25:117–132

    Article  PubMed  CAS  Google Scholar 

  • Buffett-Jerrott SE, Stewart SH, Teehan MD (1998) A further examination of the time-dependent effects of oxazepam and lorazepam on implicit and explicit memory. Psychopharmacology (Berl) 138:344–353

    Article  CAS  Google Scholar 

  • Burt DB, Zembar MJ, Niederehe G (1995) Depression and memory impairment: a meta-analysis of the association, its pattern, and specificity. Psychol Bull 117:285–305

    Article  PubMed  CAS  Google Scholar 

  • Calev A, Ben-Tzvi E, Shapira B, Drexler H, Carasso R, Lerer B (1989) Distinct memory impairments following electroconvulsive therapy and imipramine. Psychol Med 19:111–119

    PubMed  CAS  Google Scholar 

  • Carvalho SC, Marcourakis T, Artes R, Gorenstein C (2002) Memory performance in panic disorder patients after chronic use of clomipramine. J Psychopharmacol 16:220–226

    PubMed  Google Scholar 

  • Cassano GB, Puca F, Scapicchio PL, Trabucchi M (2002) Paroxetine and fluoxetine effects on mood and cognitive functions in depressed nondemented elderly patients. J Clin Psychiatry 63:396–402

    PubMed  CAS  Google Scholar 

  • Correa DD, Gorenstein C (1988) Bateria de testes de momória (I). Critérios de elaboração e avaliação. Arq Bras Psicol 38:24–35

    Google Scholar 

  • Curran HV, Gorenstein C (1993) Differential effects of lorazepam and oxazepam on priming. Int Clin Psychopharmacol 8:37–42

    Article  PubMed  CAS  Google Scholar 

  • Deptula D, Pomara N (1990) Effects of antidepressants on human performance: a review. J Clin Psychopharmacol 10:105–111

    PubMed  CAS  Google Scholar 

  • Derouesne C, Lacomblez L, Thibault S, LePoncin M (1999) Memory complaints in young and elderly subjects. Int J Geriatr Psychiatry 14:291–301

    Article  PubMed  CAS  Google Scholar 

  • Elliott R (1998) The neuropsychological profile in unipolar depression. Trends Cogn Sci 2:447–454

    Article  Google Scholar 

  • Fava M (2003) Symptoms of fatigue and cognitive/executive dysfunction in major depressive disorder before and after antidepressant treatment. J Clin Psychiatry 64(Suppl 14):30–34

    PubMed  Google Scholar 

  • First MB, Spitzer RL, Gibbon M, Williams JBW (1995) Structured Clinical Interview for DSM-IV Axis I Disorders—patient edition, version 2.0 (SCID-I/P). Biometrics Research Department, New York

  • Flavell JH (1971) First discussant’s comments: what is memory development the development of? Hum Dev 14:272–278

    Article  Google Scholar 

  • Fudge JL, Perry PJ, Garvey MJ, Kelly MW (1990) A comparison of the effect of fluoxetine and trazodone on the cognitive functioning of depressed outpatients. J Affect Disord 18:275–280

    Article  PubMed  CAS  Google Scholar 

  • Furukawa TA, Takeuchi H, Hiroe T, Mashiko H, Kamei K, Kitamura T, Takahashi K (2001) Symptomatic recovery and social functioning in major depression. Acta Psychiatr Scand 103:257–261

    Article  PubMed  CAS  Google Scholar 

  • Gathercole SE (1998) The development of memory. J Child Psychol Psychiatry 39:3–27

    Article  PubMed  CAS  Google Scholar 

  • Georgieff N, Dominey PF, Michel F, Marie-Cardine M, Dalery J (1998) Anomia in major depressive state. Psychiatry Res 77:197–208

    Article  PubMed  CAS  Google Scholar 

  • Geretsegger C, Bohmer F, Ludwig M (1994) Paroxetine in the elderly depressed patient: randomized comparison with fluoxetine of efficacy, cognitive and behavioural effects. Int Clin Psychopharmacol 9:25–29

    Article  PubMed  CAS  Google Scholar 

  • Glass RM, Uhlenhuth EH, Hartel FW, Matuzas W, Fischman MW (1981) Cognitive dysfunction and imipramine in outpatient depressive. Arch Gen Psychiatry 38:1048–1051

    PubMed  CAS  Google Scholar 

  • Gorenstein C, Pompeia S, Andrade L (1995a) Scores of Brazilian University students on the Beck Depression and the State Trait Anxiety Inventories. Psychol Rep 77:635–641

    PubMed  CAS  Google Scholar 

  • Gorenstein C, Bernik MA, Pompéia S, Marcourakis T (1995b) Impairment of performance associated with long-term use of benzodiazepines. J Psychopharmacol 9:313–318

    Article  CAS  Google Scholar 

  • Graf P, Schacter DL (1985) Implicit and explicit memory for new associations in normal and amnesic subjects. J Exp Psychol Learn Mem Cogn 11:501–518

    Article  PubMed  CAS  Google Scholar 

  • Guy W (1976) ECDEU assessment manual for psychopharmacology, revisada edn. NIMH, Rockville, MD

  • Hale AS, Pinninti NR (1995) Critical flicker threshold and anticholinergic effects of chronic antidepressant treatment in remitted depressives. J Psychopharmacol 9:258–266

    Article  CAS  Google Scholar 

  • Hamilton M (1960) A rating scale for depression. J Neurol Neurosurg Psychiatry 23:56–62

    PubMed  CAS  Google Scholar 

  • Harding TW, de Arango MV, Baltazar J, Climent CE, Ibrahim HH, Ladrido-Ignacio L, Murthy RS, Wig NN (1980) Mental disorders in primary health care: a study of their frequency and diagnosis in four developing countries. Psychol Med 10:231–241

    PubMed  CAS  Google Scholar 

  • Hindmarch I (1994) Relevant psychometric tests for antidepressants and anxiolytics. Int Clin Psychopharmacol 9(Suppl 1):27–33

    Article  PubMed  Google Scholar 

  • Kalska H, Punamaki RL, Makinen-Pelli T, Saarinen M (1999) Memory and metamemory functioning among depressed patients. Appl Neuropsychol 6:96–107

    Article  PubMed  CAS  Google Scholar 

  • Kerr JS, Fairweather DB, Hindmarch I (1993) Effects of fluoxetine on psychomotor performance, cognitive function and sleep in depressed patients. Int Clin Psychopharmacol 8:341–343

    Article  PubMed  CAS  Google Scholar 

  • Knegtering H, Eijck M, Huijsman A (1994) Effects of antidepressants on cognitive functioning of elderly patients. A review. Drugs Aging 5:192–199

    PubMed  CAS  Google Scholar 

  • Marcourakis T, Gorenstein C, Gentil V (1993) Clomipramine, a better reference drug for panic/agoraphobia II. Psychomotor and cognitive effects. J Psychopharmacol 7:325–330

    Article  CAS  Google Scholar 

  • Mari JJ, Williams P (1986) A validity study of a psychiatric screening questionnaire (SRQ-20) in primary care in the city of Sao Paulo. Br J Psychiatry 148:23–26

    PubMed  CAS  Google Scholar 

  • Meyers BS, Mattis S, Gabriele M, Kakuma T (1991) Effects of nortriptyline on memory self-assessment and performance in recovered elderly depressives. Psychopharmacol Bull 27:295–299

    PubMed  CAS  Google Scholar 

  • Neter J, Kutner MH, Nachtsheim CJ, Wasserman W (1996) Applied Linear Statistical Models, 4th edn. McGraw-Hill, Boston, MA

    Google Scholar 

  • Niederehe G, Yoder C (1989) Metamemory perceptions in depressions of young and older adults. J Nerv Ment Dis 177:4–14

    Article  PubMed  CAS  Google Scholar 

  • Peselow ED, Corwin J, Fieve RR, Rotrosen J, Cooper TB (1991) Disappearance of memory deficits in outpatient depressives responding to imipramine. J Affect Disord 21:173–183

    Article  PubMed  CAS  Google Scholar 

  • Pompeia S, Gorenstein C, Curran HV (1996) Does potency determine amnestic effects of benzodiazepines? A dose–response comparison of flunitrazepam and nitrazepam. Behav Pharmacol 7:532–539

    PubMed  CAS  Google Scholar 

  • Sakulsripong M, Curran HV, Lader M (1991) Does tolerance develop to the sedative and amnesic effects of antidepressants? A comparison of amitriptyline, trazodone and placebo. Eur J Clin Pharmacol 40:43–48

    Article  PubMed  CAS  Google Scholar 

  • Schmitt JA, Kruizinga MJ, Riedel WJ (2001) Non-serotonergic pharmacological profiles and associated cognitive effects of serotonin reuptake inhibitors. J Psychopharmacol 15:173–179

    Article  PubMed  CAS  Google Scholar 

  • Seppala T, Linnoila M, Mattila MJ (1978) Psychomotor skills in depressed out-patients treated with l-tryptophan, doxepin, or chlorimipramine. Ann Clin Res 10:214–221

    PubMed  CAS  Google Scholar 

  • Spielberg CD, Gorsuch RL, Lushene RE (1970) Manual for the State–Trait Anxiety Inventory. Consulting Psychologists Press, Palo Alto, CA

    Google Scholar 

  • Thompson PJ (1991) Antidepressants and memory: a review. Hum Psychopharmacol 6:79–90

    Article  Google Scholar 

  • Tulving E, Schacter DL (1990) Priming and human memory systems. Science 247:301–306

    Article  PubMed  CAS  Google Scholar 

  • Veiel HO (1997) A preliminary profile of neuropsychological deficits associated with major depression. J Clin Exp Neuropsychol 19:587–603

    Article  PubMed  CAS  Google Scholar 

  • Wechsler DA (1945) A standardized memory scale for clinical use. J Psychol 19:87–95

    Google Scholar 

  • Wechsler DA (1955) Manual for the Wechsler adult intelligence scale. National Foundation for Educational Research, London

    Google Scholar 

Download references

Acknowledgements

The authors acknowledge FAPESP (SCC), CNPq (RA, CG), PRONEX (RA) and PROTEM (RA) for their grants. The research was conducted at LIM-15, LIM-23 and AMBAN, HCFMUSP.

We hereby declare that the experiments comply with the current laws of Brazil, the country in which they were performed.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Clarice Gorenstein.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Gorenstein, C., de Carvalho, S.C., Artes, R. et al. Cognitive performance in depressed patients after chronic use of antidepressants. Psychopharmacology 185, 84–92 (2006). https://doi.org/10.1007/s00213-005-0274-2

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00213-005-0274-2

Keywords

Navigation