A Cross-Sectional Study of the Prevalence of Cognitive and Physical Symptoms During Long-Term Antidepressant Treatment
Abstract
BACKGROUND: Antidepressant therapies have been associated with a variety of side effects of both physical and psychological nature. Until recently, however, the majority of the studies focusing on side effects of antidepressants have not routinely included assessment of cognitive side effects. The purpose of the present work is to examine cross-sectionally the prevalence of cognitive and physical side effects of antidepressants during long-term treatment of depression. METHOD: Patients at least 18 years of age who were deemed responders to antidepressant therapy following at least 3 months of treatment for major depressive disorder (MDD) (diagnosed according to DSM-IV criteria) and whose MDD was considered to be in partial or full remission were eligible for inclusion in this study. Eligible patients were enrolled between January 2003 and December 2004. Study participants were administered the Harvard Department of Psychiatry/National Depression Screening Day (HANDS) scale, the Epworth Sleepiness Scale, the Brief Fatigue Inventory, the Massachusetts General Hospital Cognitive and Physical Functioning Questionnaire (CPFQ), and a study-specific questionnaire inquiring about the emergence of specific side effects such as apathy, fatigue, and inattentiveness. RESULTS: 117 MDD patients (mean +/- SD age: 43.4 +/- 12.6 years; women: N = 78 [66.7%]) met criteria for response according to the HANDS (score < 9). Cognitive symptoms (apathy, inattentiveness, forgetfulness, word-finding difficulty, and mental slowing) were each reported on both the CPFQ and the study-specific questionnaire by more than 30% of the responders on antidepressants. The physical symptoms of fatigue and sleepiness/sedation were reported by over 40% of the responders on both the CPFQ and the study-specific questionnaire. A significant, positive relationship was found between the CPFQ and the severity of residual depressive symptoms as measured by the HANDS total score (F = 15.3, p = .0002). CONCLUSION: Physical and cognitive symptoms are frequently reported by MDD patients who have responded to antidepressants and are treated in the long term with these agents. It is likely that these symptoms are both side effects of the antidepressants as well as residual symptoms of MDD.
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There are a few data suggesting that emotional blunting may be quite prevalent.
“There are a few data suggesting that emotional blunting may be quite prevalent.”
From Emotional blunting with antidepressant treatments: A survey among depressed patients (2017) · cites this paper as Fava et al., 2006
A cross-sectional study in 117 patients with major depressive disorder found that about 30% of patients on SSRI had some form of apathy.
“Similarly, a cross-sectional study in 117 patients with major depressive disorder found that about 30% of patients on SSRI had some form of apathy (Fava et al., 2006).”
From Emotional blunting with antidepressant treatments: A survey among depressed patients (2017) · cites this paper as Fava et al., 2006
The observed rates of emotional blunting are in accord with rates suggested in previous studies.
“are in accord with rates suggested in previous studies (Opbroek et al., 2002; Bolling and Kohlenberg, 2004; Fava et al., 2006).”
From Emotional blunting with antidepressant treatments: A survey among depressed patients (2017) · cites this paper as Fava et al., 2006
Emotional blunting may persist even after depressive symptoms have improved and may occur in patients of all ages.
“Such adverse affective manifestations may persist even after the symptoms of depression have improved and may ensue in patients of all ages [63].”
There are many reports of cognitive impairments that remain following antidepressant treatment that successfully reduces depressive symptomatology, even when remission of depressive symptoms is obtained.
“In contrast, there are many reports of cognitive impairments that remain following antidepressant treatment that successfully reduces depressive symptomatology [19–21], even when remission of depressive symptoms is obtained [22–24].”
Long-term antidepressant treatment (generally lasting more than 6 months) can have a detrimental impact on executive function, memory, attention, and motivation in patients with MDD.
“Some studies have suggested that long-term antidepressant treatment (generally lasting more than 6 months) can have a detrimental impact on executive function, memory, attention, and motivation in patients with MDD (Fava et al., 2006; Popovic et al., 2015; Bortolato et al., 2016).”
From Aerobic Exercise as a Tool to Improve Hippocampal Plasticity and Function in Humans: Practical Implications for Mental Health Treatment (2016) · cites this paper as Fava et al., 2006
Treatment with antidepressants has been associated with increased cognitive deficits, such as apathy, inattentiveness, forgetfulness, word-finding difficulty, and mental slowing, in depressed individuals reaching partial or full remission (n = 117).
“For instance, treatment with antidepressants has been associated with increased cognitive deficits, such as apathy, inattentiveness, forgetfulness, word-finding difficulty, and mental slowing, in depressed individuals reaching partial or full remission (n = 117) [80].”
From Cognitive remission: a novel objective for the treatment of major depression? (2016) · cites this paper as [80]
Long-term therapy with certain antidepressants may be linked to cognitive side effects in adult subjects with major depressive disorder.
“Long-term therapy with certain antidepressants may also be linked to cognitive side effects in adult subjects with MDD.”
From Cognitive remission: a novel objective for the treatment of major depression? (2016) · cites this paper as [80]
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- Authors
- Fava, M., Graves, L. M., Benazzi, F., Scalia, M. J., Iosifescu, D. V., Alpert, J. E., & Papakostas, G. I.
- Affiliations
- Harvard University (US)
- University of California San Diego (US)
- Venue
- The Journal of Clinical Psychiatry
- Publisher
- Physicians Postgraduate Press, Inc
- Published
- 2006-11-15
- Volume
- 67
- Issue
- 11
- Pages
- 1754-1759
- ISSN
- 0160-6689 (ISSN-L)
- OpenAlex
- W1973988192
- Cited by
- 229
- References
- 0
- Citations by year
- 2026: 3 · 2025: 7 · 2024: 12 · 2023: 9 · 2022: 11 · 2021: 9 · 2020: 8 · 2019: 5 · 2018: 17 · 2017: 13 · 2016: 18 · 2015: 22 · 2014: 20 · 2013: 17 · 2012: 11
- FWCI
- 4.39
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- The Journal of Clinical Psychiatry (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Pharmacology › Treatment of Major Depression
- Health Sciences › Medicine › Psychiatry and Mental health › Schizophrenia research and treatment
- Social Sciences › Psychology › Experimental and Cognitive Psychology › Anxiety, Depression, Psychometrics, Treatment, Cognitive Processes
- Keywords
- antidepressant side effects, cognitive side effects, physical side effects, major depressive disorder, long-term antidepressant treatment, fatigue, sleepiness, sedation, apathy, inattention, residual depressive symptoms, cognitive slowing, depression remission
- MeSH terms
- Adult, Antidepressive Agents, Chronic Disease, Cognition Disorders, Cross-Sectional Studies, Major Depressive Disorder, Fatigue, Female, Humans, Male, Population Surveillance, Sleep Stages, Prevalence
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