Early Symptomatic Worsening During Treatment With Fluoxetine in Major Depressive Disorder: Prevalence and Implications
Abstract
BACKGROUND: A subset of patients experience worsening of depressed mood after beginning antidepressant treatment, which could represent the natural history of the illness or a treatment-related effect. While patterns of response have been examined as possible predictors of outcome, the clinical correlates and implications of early worsening per se have not been investigated. METHOD: In a post hoc analysis, we studied the clinical correlates of early worsening in a large sample of outpatients (N = 694) diagnosed with a DSM-III-R-defined major depressive episode and treated with fluoxetine (20 mg/day) for up to 12 weeks. We defined early worsening as an increase of at least 5 points on a modified 17-item Hamilton Rating Scale for Depression (mHAM-D, including reverse vegetative symptoms) compared to the previous visit, and occurring during the acute phase of treatment. The primary analysis compared remission and response at week 12 between those patients with and without worsening. RESULTS: In our sample, 211 patients (30.4%) experienced early worsening of depression. An increase in mHAM-D score at week 2, 3, 4, or 6 was associated with a significantly lower probability of remission and response at both week 8 and week 12, while no significant difference was observed in study discontinuation. Baseline features, including gender, age, mHAM-D score at entry, number of previous depressive episodes, and duration of illness were not associated with the development of early worsening during fluoxetine treatment. CONCLUSION: Early clinical worsening is common and associated with a decreased likelihood of achieving remission.
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The occurrence of paradoxical effects was reported in double-blind placebo-controlled investigations that were concerned with fluoxetine and sertraline.
“The occurrence of paradoxical effects was reported in double-blind placebo-controlled investigations that were concerned with fluoxetine and sertraline.”
From May antidepressant drugs worsen the conditions they are supposed to treat? The clinical foundations of the oppositional model of tolerance (2020) · cites this paper as [28]
Depressive symptoms reappeared again when fluoxetine was administered.
“Depressive symptoms reappeared again when fluoxetine was administered.”
From May antidepressant drugs worsen the conditions they are supposed to treat? The clinical foundations of the oppositional model of tolerance (2020) · cites this paper as [28]
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- Authors
- Cusin, C., Fava, M., Amsterdam, J. D., Quitkin, F. M., Reimherr, F. W., Beasley, C. M., Rosenbaum, J. F., & Perlis, R. H.
- Affiliations
- Harvard University (US)
- University of Pennsylvania (US)
- Columbia University (US)
- Eli Lilly (United States) (US)
- Venue
- The Journal of Clinical Psychiatry
- Publisher
- Physicians Postgraduate Press, Inc
- Published
- 2007-01-15
- Volume
- 68
- Issue
- 01
- Pages
- 52-57
- ISSN
- 0160-6689 (ISSN-L)
- OpenAlex
- W2056881294
- Cited by
- 22
- References
- 0
- Citations by year
- 2026: 1 · 2024: 2 · 2023: 1 · 2020: 2 · 2017: 2 · 2016: 2 · 2015: 2 · 2014: 1
- FWCI
- 1.78
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- The Journal of Clinical Psychiatry (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institute of Mental Health (K23MH067060)
- Topics
- Health Sciences › Medicine › Pharmacology › Treatment of Major Depression
- Social Sciences › Psychology › Experimental and Cognitive Psychology › Anxiety, Depression, Psychometrics, Treatment, Cognitive Processes
- Social Sciences › Psychology › Clinical Psychology › Psychotherapy Techniques and Applications
- Keywords
- fluoxetine, major depressive disorder, early treatment response, remission, treatment response prediction, Hamilton Depression Rating Scale, outpatients, antidepressant side effects
- MeSH terms
- Adult, Clinical Trials as Topic, Major Depressive Disorder, Depressive Disorder, Major, Female, Fluoxetine, Humans, Male, Middle Aged, Prognosis, Retrospective Studies, Prevalence, Selective Serotonin Reuptake Inhibitors, Disease Progression
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