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Paroxetine and Fluoxetine Effects On Mood and Cognitive Functions in Depressed Nondemented Elderly Patients
Abstract
BACKGROUND: A large proportion of the elderly population complains of depressive symptoms. The ideal antidepressant for these patients, who often suffer from numerous concomitant diseases, should not worsen their cognitive functions and should be free of contraindications. METHOD: To assess the effects of 2 selective serotonin reuptake inhibitors on cognitive functions in elderly depressed patients (ICD-10 criteria), we conducted a double-blind, randomized, parallel-group, multicenter study comparing paroxetine (20-40 mg daily) and fluoxetine (20-60 mg daily) treatment for 1 year. Cognitive performance was evaluated by means of the Buschke Selective Reminding Test, the Blessed Information and Memory Test, the Clifton Assessment Schedule, the Cancellation Task Test, and the Wechsler Paired Word Test; the Hamilton Rating Scale for Depression (HAM-D) and the Clinical Anxiety Scale were administered to assess the course of depressive and anxiety symptoms, respectively. RESULTS: 242 patients were enrolled (mean +/- SD age = 75.4 +/- 6.6 years). During the study, no deterioration of cognition was observed; on the contrary, most of the tested cognitive functions improved. Good antidepressant efficacy was maintained for over 1 year with both drugs, based on the percentage of responders to treatment (patients achieving a HAM-D total score < 10; 60%). Both drugs showed a good tolerability and safety profile. CONCLUSION: The 2 antidepressants proved to be suitable for the long-term treatment of depression in the elderly and to be devoid of detrimental effects on the tested cognitive functions.
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“Treatment with selective serotonin reuptake inhibitors (SSRIs) has resulted in improved attention, memory, and learning [14]”
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Hippocampal volume, memory, and cortisol status in major depressive disorder: Effects of treatment
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“, 2002 (28)¶ 242 75 56 52 Fluoxetine, 20–60 mg/d, vs.”
BackgroundMethodInfluentialFluoxetine versus other types of pharmacotherapy for depression
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“…RCTs could not be included because 2 antidepressants from the same class were compared with each other (Bayer et al., 1989; Brion et al., 1996; Cassano et al., 2002; De Vanna et al., 1990; Fairbairn et al., 1989; Finkel et al., 1999; Geretsegger et al., 1994; Gwirtsman et al., 1983; Nair et…”
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“For example, improvement in episodic memory has been reported after SSRI treatment such as fluoxetine (Levkovitz et al., 2002; Battista-Cassano et al., 2002; Gallassi et al., 2006) and paroxetine (Battista-Cassano et al.”
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“, 2002([102]) 242 52 weeks Fluoxetine 20-60 Paroxetine 20-40 33 vs.”
BackgroundInfluentialFluoxetine versus other types of pharmacotherapy for depression
Cipriani, A., Brambilla, P., Furukawa, T. A., Geddes, J. R., Gregis, M., Hotopf, M. H., Malvini, L., & Barbui, C. (2005) · Cochrane Database of Systematic Reviews · doi:10.1002/14651858.cd004185.pub2 · Cited by 146
Fluoxetine improves the memory deficits caused by the chemotherapy agent 5-fluorouracil
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Herrera-Guzmán, I., Herrera-Abarca, J. E., Gudayol-Ferré, E., Herrera-Guzmán, D., Gómez-Carbajal, L., Peña-Olvira, M., Villuendas-González, E., & Joan, G.-O. (2010) · Psychiatry Research · doi:10.1016/j.psychres.2010.03.006 · Cited by 120
“, 2002; Battista-Cassano et al., 2002; Wroolie et al., 2006). A similar effect has been found in the imipramine tricyclic antidepressant (Koetsier et al., 2002), and in reboxetine, a noradrenaline-selective re-uptake inhibitor (Fergusson et al., 2003). The work by Raskin et al. (2007) does not show attention improveme…”
BackgroundResultEscitalopram in the Treatment of Depressed Elderly Patients
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“Likewise, newer anticonvulsants (Brunbech and Sabers, 2002; Ortinski and Meador, 2004; Daban et al., 2006a), newer antidepressants (Cassano et al., 2002), and atypical antipsychotics (Reinares et al., 2000; MacQueen and Young, 2003) cause little or no cognitive impairment when used in the…”
Adverse Effects of Pharmacologic Treatments of Major Depression in Older Adults
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“Consistent with this hypothesis, serotonergic treatments attenuate depression-related dysfunction in cognitive domains such as episodic memory, working memory, attention, and executive function (Cassano et al., 2002; Constant et al., 2005; Herrera-Guzman et al., 2009, 2010a; Levkovitz et al., 2002), although it should…”
BackgroundParoxetine—The Antidepressant from Hell? Probably Not, But Caution Required
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Paroxetine versus other anti-depressive agents for depression
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“Preliminary studies with SSRI agents such as citalopram, fluoxetine or paroxetine, showed reduction of irritability [114] and no side effects on cognitive impairment [115].”
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“Studies with SSRIs have demonstrated memory and psychomotor performance improvements after fluoxetine in adults (Hale and Pinninti 1995) and elderly depressed patients (Kerr et al. 1993; Geretsegger et al. 1994; Cassano et al. 2002).”
BackgroundQuality of life and function after electroconvulsive therapy
McCall, W. V., Dunn, A. G., & Rosenquist, P. B. (2004) · The British Journal of Psychiatry · doi:10.1192/bjp.185.5.405 · Cited by 55
“Similar findings of improved cognition have been reported in stroke patients recovering from depression (Narushima et al, 2003) and in clinical trials of antidepressant medication in primary depression (Reynolds et al, 1987; Reifler et al, 1989; Newhouse et al, 2000; Cassano et al, 2002).”
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“Improvement of cognition with SSRIs was also obtained utilizing sertraline (Constant et al., 2005), fluoxetine (Levkovitz et al., 2002) and paroxetine (Cassano et al., 2002).”
MethodSelf-citationSSRIs and cognitive performance in a working sample
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“…that paroxetine is devoid of detrimental effects on cognitive functions either in normal subjects or in depressed patients; however, no major improvement in the cognitive performance has been shown in either study (Cassano et al. 2002; Ferguson et al. 2003; for review, see Nebes et al. 2003).”
BackgroundEffects of fluoxetine on hippocampal-dependent and hippocampal-independent learning tasks
Valluzzi, J. A., & Chan, K. (2007) · Behavioural Pharmacology · doi:10.1097/fbp.0b013e3282ee2a91 · Cited by 45
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Long-term effects of antidepressants on cognition in patients with Alzheimer's disease
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“Studies with SSRIs in the elderly have shown cognitive improvements in elderly patients without AD (14, 16).”
BackgroundEvidence-Based Pharmacologic Interventions for Geriatric Depression
Shanmugham, B., Karp, J. F., Drayer, R. A., Reynolds, C. F., & Alexopoulos, G. S. (2005) · Psychiatric Clinics of North America · doi:10.1016/j.psc.2005.09.012 · Cited by 30
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“Paroxetine and fluoxetine improved most of the tested cognitive functions in a study of 242 depressed patients during one year [277].”
BackgroundBupropion normalizes cognitive performance in patients with depression.
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(R)-fluoxetine enhances cognitive flexibility and hippocampal cell proliferation in mice
Marwari, S., & Dawe, G. S. (2018) · Journal of Psychopharmacology · doi:10.1177/0269881118754733 · Cited by 30
“Major depressive disorder (MDD) involves neuropsychological alterations not only in emotional responses but also across a broad dimension of cognitive function.”
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“, 2011), whereas newer antidepressants such as selective serotonin- or serotonin/ noradrenalin reuptake inhibitors (SSRIs/SNRIs) as well as atypical neuroleptics received by the vast majority of our patients are rather expected to exert beneficial effects in cognitive functioning (Austin et al., 2001; Cassano et al.,…”
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Memory Loss in a Patient Treated with Fluoxetine
Joss, J. D., Burton, R. M., & Keller, C. A. (2003) · Annals of Pharmacotherapy · doi:10.1345/aph.1d154 · Cited by 25
Effects of remission speed and improvement of cognitive functions of depressed patients
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“Fluoxetine, the same SSRI used in this study, can improve memory and mental processing speed (Battista-Cassano et al., 2002; Levkovitz et al., 2002; Finkel et al., 1999; Newhouse et al., 2000; Gallassi et al., 2006).”
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“, 2002 [44] Clearly industry Paroxetine, 20e40 Fluoxetine, 20e60 242; 52 NR Fair De Wilde et al.”
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Use of paroxetine for the treatment of depression and anxiety disorders in the elderly: a review
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“This finding may be particularly significant, since depression in the elderly is often associated with decline of cognitive symptoms, and even mild cognitive impairment or dementia [64–67].”
BackgroundWhen ageing meets the blues: Are current antidepressants effective in depressed aged patients?
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“Antidepressants differentially affect cognition depending on their receptor-binding profiles (Furlan et al. 2001 ; Cassano et al. 2002 ; Riedel et al. 2005 ; Gualtieri & Johnson, 2007).”
BackgroundDrug Class Review: Second-Generation Antidepressants
Gartlehner, G., Hansen, R. A., Reichenpfader, U., Kaminski, A., Kien, C., Strobelberger, M., Noord, M. V., Thieda, P., Thaler, K. J., & Gaynes, B. N. (2011) · Cited by 17
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Ampuero, E., Luarte, A., Flores, F. S., Soto, A. I., Pino, C. H., Silva, V., Erlandsen, M., Concha, T., & Wyneken, Ú. (2024) · Frontiers in Pharmacology · doi:10.3389/fphar.2024.1412420 · Cited by 23
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“In 242 elderly depressed patients treated with paroxetine or fluoxetine, no deterioration of cognition was observed (21).”
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“…longer (Barch et al., 2012; Beheydt et al., 2015; Bondareff et al., 2000; Brendel et al., 2018; Butters et al., 2000, 2011; Carrière et al., 2017; Cassano et al., 2002; Choe et al., 2016; Del Ser et al., 2019; Devanand et al., 2003; Jorge et al., 2010; Leng et al., 2018; Lenze et al., 2020;…”
ResultInfluentialGudayol‐Ferré, E., Herrera‐Guzmán, I., Camarena, B., Cortés‐Penagos, C., Herrera‐Abarca, J. E., Martínez‐Medina, P., Asbún‐Bojalil, J., Lira‐Islas, Y., Reyes‐Ponce, C., & Guàrdia‐Olmos, J. (2012) · Human Psychopharmacology Clinical and Experimental · doi:10.1002/hup.2267 · Cited by 15
“Several works have likewise proved that chronic treatment with AD improves the neuropsychological alterations of MDD (Battista-Cassano et al., 2002; Constant et al., 2005; Herrera-Guzmán et al., 2009, 2010a, 2010b).”
BackgroundOyeyemi, D. M., Cooter, M. L., Chung, S., Whitson, H. E., Browndyke, J. N., Devinney, M. J., Smith, P. J., Garrigues, G. E., Moretti, E., Moul, J. W., et al. (2020) · Journal of Geriatric Psychiatry and Neurology · doi:10.1177/0891988720978791 · Cited by 16
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Hippocampal 5-HT1A receptor binding is related to object–location memory in humans
Glikmann‐Johnston, Y., Saling, M. M., Chen, J., O'Keefe, G. J., Gong, S. J., Tochon‐Danguy, H., Mulligan, R. S., & Reutens, D. C. (2014) · Brain Structure and Function · doi:10.1007/s00429-013-0675-7 · Cited by 13
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“This study did not find cognitive decline with the use of paroxetine and fluoxetine.(38) The current study used real-world data and found that there is no significant difference in cognition across the 2 treatment groups.”
BackgroundHerrera‐Guzmán, I., Gudayol‐Ferré, E., Jarne-Esparcia, A. J., Herrera‐Abarca, J. E., Herrera-Guzmán, D., Peró, M., & Guàrdia‐Olmos, J. (2009) · The European Journal of Psychiatry · doi:10.4321/s0213-61632009000100001 · Cited by 11
Effects of sertraline, duloxetine, vortioxetine, and idazoxan in the rat affective bias test
Refsgaard, L. K., Haubro, K., Pickering, D. S., Stuart, S. A., Robinson, E. S. J., & Andreasen, J. T. (2016) · Psychopharmacology · doi:10.1007/s00213-016-4407-6 · Cited by 13
“, 2013) and conventional antidepressants (Raskin et al., 2007; Greer et al., 2014; Katona et al., 2012; Herrera-Guzmán et al., 2009; Gallassi et al., 2006; Cassano et al., 2002; CulangReinlieb et al., 2012) in humans, although some inconsistencies in the literature exist (Ferguson et al.”
BackgroundInhibition of TNBC Cell Growth by Paroxetine: Induction of Apoptosis and Blockage of Autophagy Flux
Huang, Q., Wu, M., Pu, Y., Zhou, J., Zhang, Y., Li, R., Xia, Y., Zhang, Y., & Ma, Y. (2024) · Cancers · doi:10.3390/cancers16050885 · Cited by 14
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Li, X., Shao, J., Wang, H., Wang, X., Zhu, R., Yao, Z., & Lü, Q. (2022) · European Radiology · doi:10.1007/s00330-022-09004-x · Cited by 10
The role of encoding strategies in contextual memory deficits in patients with bipolar disorder
Corrêa, M. S., da Silveira, E. M. S., de Lima, D. B., Balardin, J. B., Walz, J. C., Kapczinski, F. P., & Bromberg, E. (2014) · Neuropsychological Rehabilitation · doi:10.1080/09602011.2014.969281 · Cited by 10
Cognitive Difficulties Associated With Depression What Are the Implications for Treatment
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“In contrast, we could not detect in MDD patients an improvement in their attention and working memory as reported by others (Cassano et al., 2002; Jaeger et al., 2006).”
ResultSecond-Generation Antidepressants in the Pharmacologic Treatment of Adult Depression
Gartlehner, G., Hansen, R. A., Morgan, L. C., Thaler, K. J., Lux, L. J., Noord, M. V., Mager, U., Gaynes, B. N., Thieda, P., Strobelberger, M., et al. (2011) · Cited by 8
Krzysztoforska, K., Piechal, A., Wojnar, E., Blecharz‐Klin, K., Pyrzanowska, J., Joniec‐Maciejak, I., Krzysztoforski, J., & Widy‐Tyszkiewicz, E. (2023) · Nutrients · doi:10.3390/nu15030625 · Cited by 7
“In turn, studies of selective serotonin reuptake inhibitors have shown that enhanced serotonergic transmission improves the performance of many declarative memory tasks in both animals and humans, prevents the development of pharmacologically induced amnesia, and improves memory consolidation and retrieval in mice [39…”
BackgroundInternational Dosage Differences in Fluoxetine Clinical Trials
Patten, S. B., Cipriani, A., Brambilla, P., Nosè, M., & Barbui, C. (2005) · The Canadian Journal of Psychiatry · doi:10.1177/070674370505000107 · Cited by 7
Pharmacotherapy of Late-Life Depression: Evidence-Based Recommendations
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Antidepressant Treatment of Geriatric Depression
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Gartlehner, G., Hansen, R. A., Kahwati, L. C., Lohr, K. N., Gaynes, B. N., & Carey, T. (2006) · Cited by 5
Klinisch-Neuropsychologische Aspekte der Therapie mit Psychopharmaka
Brunnauer, A., & Laux, G. (2010) · Springer eBooks · doi:10.1007/978-3-540-72340-0_25 · Cited by 3
Neuropsychological Performance in Remitted Major Depressive Disorder Patients: A Case-Control Study
Ahmed Souhali Bannour Mtiraoui, A. (2013) · Journal of Depression & Anxiety · doi:10.4172/2167-1044.1000136 · Cited by 3
Les antidépresseurs dans le traitement de la dépression de la personne âgée
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Working Memory in Patients with Major Depressive Disorder
Kaneda, Y. (2012) · Psychology · doi:10.4236/psych.2012.329115 · Cited by 4
“Cassano et al. (2002), in their double-blind, randomized, parallel-group, multicenter study comparing paroxetine and fluoxetine treatment for 1 year, found that improvement, rather than deterioration, was observed in most of the tested cognitive functions.”
BackgroundBastos, A. G., & Trentini, C. M. (2013) · Psicologia Teoria e Pesquisa · doi:10.1590/s0102-37722013000400010 · Cited by 3
Adverse Effects of Pharmacological Treatments of Major Depression in Older Adults
Sobieraj, D. M. (2019) · doi:10.23970/ahrqepccer215 · Cited by 3
Shi, H., Li, Q., Hu, F., Liu, Y., & Wang, K. (2025) · Translational Psychiatry · doi:10.1038/s41398-025-03291-w · Cited by 2
National patterns of paroxetine use among US Medicare patients from 2015–2020
Cavanah, L. R., Goldhirsh, J. L., Huey, L. Y., & Piper, B. J. (2024) · Frontiers in Psychiatry · doi:10.3389/fpsyt.2024.1399493 · Cited by 4
Medications and Cognition in Older Adults
Caporaso, G. L. (2012) · Springer eBooks · doi:10.1007/978-1-4614-3106-0_7 · Cited by 2
Liu, S., Ma, X., Yin, M., Zhu, H., Zhao, Y., Nelson, B., Jia Liu, B., & Jia, H. (2014) · Chinese Science Bulletin · doi:10.1007/s11434-014-0198-5 · Cited by 2
Myczkowski, M. L. (2009) · Digital Library of Theses and Dissertations (Universidade de São Paulo) · doi:10.11606/d.5.2009.tde-09122009-111406 · Cited by 4
Specialty-type and state-level variation in paroxetine use among older adult patientsPreprint
Cavanah, L. R., Goldhirsh, J. L., Huey, L. Y., et al. (2023) · medRxiv · doi:10.1101/2023.02.15.23285973 · Cited by 2
Metadata
- Authors
- Cassano, G. B., Puca, F., Scapicchio, P. L., Trabucchi, M., & Italian Study Group on Depression in Elderly Patients
- Affiliations
- University of Pisa (IT)
- Venue
- The Journal of Clinical Psychiatry
- Publisher
- Physicians Postgraduate Press, Inc
- Published
- 2002-05-15
- Volume
- 63
- Issue
- 5
- Pages
- 396-402
- ISSN
- 0160-6689 (ISSN-L)
- OpenAlex
- W2046119291
- Cited by
- 121
- References
- 0
- Citations by year
- 2025: 3 · 2024: 4 · 2023: 3 · 2022: 5 · 2021: 1 · 2020: 1 · 2019: 7 · 2018: 2 · 2017: 1 · 2016: 2 · 2015: 4 · 2014: 9 · 2013: 7 · 2012: 8
- FWCI
- 4.24
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- The Journal of Clinical Psychiatry (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Pharmacology (medical) › Treatment of Major Depression
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Social Sciences › Psychology › Experimental and Cognitive Psychology › Anxiety, Depression, Psychometrics, Treatment, Cognitive Processes
- Keywords
- paroxetine, fluoxetine, selective serotonin reuptake inhibitors, geriatric depression, cognitive function, long-term antidepressant treatment, antidepressant efficacy, safety and tolerability, anxiety symptoms
- MeSH terms
- Affect, Age Factors, Aged, Ambulatory Care, Anxiety Disorders, Cognition, Depressive Disorder, Double-Blind Method, Female, Fluoxetine, Humans, Male, Psychiatric Status Rating Scales, Survival Analysis, Treatment Outcome, Selective Serotonin Reuptake Inhibitors, Paroxetine
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