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Cited by 221Treatment of Major DepressionNeural and Behavioral Psychology StudiesAnxiety, Depression, Psychometrics, Treatment, Cognitive Processes

Executive dysfunction predicts nonresponse to fluoxetine in major depression

Dunkin, Jennifer J, Leuchter, Andrew F, Cook, Ian A, Kasl-Godley, Julia E, Abrams, Michelle, Rosenberg-Thompson, Susan·2000·Journal of Affective Disorders
DOI 10.1016/s0165-0327(99)00157-3
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Abstract

Background Functional brain imaging studies of major depression have consistently revealed hypometabolism or hypoperfusion in specific regions of the prefrontal cortex and basal ganglia. Studies of cognitive functioning in major depression have suggested that some but not all subjects exhibit cognitive deficits that are consistent with frontal-subcortical dysfunction, although the reasons for this heterogeneity are unclear. In this study, we explored this heterogeneity among depressed subjects by examining the relationship between cognitive functioning and treatment outcome.Method Subjects with major depression were administered a complete neuropsychological test battery prior to treatment with fluoxetine.Results There were no significant differences between responders and nonresponders to fluoxetine in terms of age, educational achievement, number of past episodes of depression, and estimated premorbid IQ. However, nonresponders performed significantly worse than responders on several pretreatment measures of executive functioning, after controlling for baseline group differences in depression severity.Limitations The results are based on a small sample of primarily female subjects, resulting in low statistical power and less generalizability to samples of male subjects with depression.Conclusions The findings suggest that subtle prefrontal dysfunction in subjects with major depression may be predictive of poor response with particular medications. Assessment of the executive functions may play a particular role in pretreatment identification of subjects likely to respond to specific medications.

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  • Poor cognitive functioning is thought to contribute to the development and maintenance of psychiatric disorders, where executive dysfunction impacts negatively on response to pharmacological and non-pharmacological treatments for psychiatric disorders including mood disorders and PTSD.

    “Critically, poor cognitive functioning is thought to contribute to the development and maintenance of these disorders, where, for example, executive dysfunction impacts negatively on response to pharmacological and non-pharmacological treatments for psychiatric disorders including mood disorders and PTSD (Dunkin et al., 2000;Polak”

    From A review of the relation between dissociation, memory, executive functioning and social cognition in military members and civilians with neuropsychiatric conditions (2016) · cites this paper as Dunkin et al., 2000

  • Some pilot studies show that cognitive deficits in major depressive disorder patients may predict non-response to treatment with selective serotonin reuptake inhibitors or dual serotonergic-noradrenergic reuptake inhibitors.

    “Furthermore, some pilot studies show that cognitive deficits in MDD patients may predict non-response to treatment with selective serotonin reuptake inhibitors (SSRIs) or dual serotonergic-noradrenergic reuptake inhibitors (SNRIs), indicating that poor performance in selected cognitive domains may define a patient subgroup that requires complex or additional treatment [21–23].”

    From Cognitive remission: a novel objective for the treatment of major depression? (2016) · cites this paper as [21]

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Authors
Dunkin, J. J., Leuchter, A. F., Cook, I. A., Kasl-Godley, J. E., Abrams, M., & Rosenberg-Thompson, S.
Affiliations
University of California, Los Angeles (US)
Corresponding author
Dunkin, Jennifer J
ORCID
Venue
Journal of Affective Disorders
Publisher
Elsevier BV
Published
2000-10
Volume
60
Issue
1
Pages
13-23
ISSN
0165-0327 (ISSN-L)
DOI
10.1016/s0165-0327(99)00157-3
OpenAlex
W2047261130
Cited by
221
References
54
Citations by year
2026: 2 · 2025: 3 · 2024: 8 · 2023: 4 · 2022: 8 · 2021: 9 · 2020: 7 · 2019: 3 · 2018: 13 · 2017: 9 · 2016: 12 · 2015: 16 · 2014: 6 · 2013: 20 · 2012: 11
FWCI
1.73
Type
journal article
Language
en
Open access
closed
Licence
www.elsevier.com/tdm/userlicense/1.0/ (tdm)
Locations
  • Journal of Affective Disorders (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • National Institutes of Health (5r01mh040705-13)
  • National Institute of Mental Health (R01MH40705)
Topics
  • Health Sciences › Medicine › Pharmacology › Treatment of Major Depression
  • Life Sciences › Neuroscience › Cognitive Neuroscience › Neural and Behavioral Psychology Studies
  • Social Sciences › Psychology › Experimental and Cognitive Psychology › Anxiety, Depression, Psychometrics, Treatment, Cognitive Processes
Keywords
major depressive disorder, executive dysfunction, fluoxetine, treatment non-response, cognitive impairment, prefrontal cortex, treatment outcome prediction, neuropsychological assessment, antidepressant response
MeSH terms
Adult, Cognition Disorders, Major Depressive Disorder, Double-Blind Method, Female, Fluoxetine, Humans, Male, Neuropsychological Tests, Predictive Value of Tests, Severity of Illness Index, Single-Blind Method, Treatment Failure, Selective Serotonin Reuptake Inhibitors, Prefrontal Cortex

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