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.
Similar content being viewed by others
Notes
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
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
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
APA (1994) Diagnostic and statistical manual of mental disorders, 4th edn. American Psychiatric Association, Washington, DC
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
Beck AT, Ward CH, Mendelson M, Mock J, Erbaugh J (1961) An inventory for measuring depression. Arch Gen Psychiatry 4:561–571
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
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
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
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
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
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
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
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
Correa DD, Gorenstein C (1988) Bateria de testes de momória (I). Critérios de elaboração e avaliação. Arq Bras Psicol 38:24–35
Curran HV, Gorenstein C (1993) Differential effects of lorazepam and oxazepam on priming. Int Clin Psychopharmacol 8:37–42
Deptula D, Pomara N (1990) Effects of antidepressants on human performance: a review. J Clin Psychopharmacol 10:105–111
Derouesne C, Lacomblez L, Thibault S, LePoncin M (1999) Memory complaints in young and elderly subjects. Int J Geriatr Psychiatry 14:291–301
Elliott R (1998) The neuropsychological profile in unipolar depression. Trends Cogn Sci 2:447–454
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
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
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
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
Gathercole SE (1998) The development of memory. J Child Psychol Psychiatry 39:3–27
Georgieff N, Dominey PF, Michel F, Marie-Cardine M, Dalery J (1998) Anomia in major depressive state. Psychiatry Res 77:197–208
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
Glass RM, Uhlenhuth EH, Hartel FW, Matuzas W, Fischman MW (1981) Cognitive dysfunction and imipramine in outpatient depressive. Arch Gen Psychiatry 38:1048–1051
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
Gorenstein C, Bernik MA, Pompéia S, Marcourakis T (1995b) Impairment of performance associated with long-term use of benzodiazepines. J Psychopharmacol 9:313–318
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
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
Hamilton M (1960) A rating scale for depression. J Neurol Neurosurg Psychiatry 23:56–62
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
Hindmarch I (1994) Relevant psychometric tests for antidepressants and anxiolytics. Int Clin Psychopharmacol 9(Suppl 1):27–33
Kalska H, Punamaki RL, Makinen-Pelli T, Saarinen M (1999) Memory and metamemory functioning among depressed patients. Appl Neuropsychol 6:96–107
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
Knegtering H, Eijck M, Huijsman A (1994) Effects of antidepressants on cognitive functioning of elderly patients. A review. Drugs Aging 5:192–199
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
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
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
Neter J, Kutner MH, Nachtsheim CJ, Wasserman W (1996) Applied Linear Statistical Models, 4th edn. McGraw-Hill, Boston, MA
Niederehe G, Yoder C (1989) Metamemory perceptions in depressions of young and older adults. J Nerv Ment Dis 177:4–14
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
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
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
Schmitt JA, Kruizinga MJ, Riedel WJ (2001) Non-serotonergic pharmacological profiles and associated cognitive effects of serotonin reuptake inhibitors. J Psychopharmacol 15:173–179
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
Spielberg CD, Gorsuch RL, Lushene RE (1970) Manual for the State–Trait Anxiety Inventory. Consulting Psychologists Press, Palo Alto, CA
Thompson PJ (1991) Antidepressants and memory: a review. Hum Psychopharmacol 6:79–90
Tulving E, Schacter DL (1990) Priming and human memory systems. Science 247:301–306
Veiel HO (1997) A preliminary profile of neuropsychological deficits associated with major depression. J Clin Exp Neuropsychol 19:587–603
Wechsler DA (1945) A standardized memory scale for clinical use. J Psychol 19:87–95
Wechsler DA (1955) Manual for the Wechsler adult intelligence scale. National Foundation for Educational Research, London
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
Corresponding author
Rights 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
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00213-005-0274-2