Early symptomatic worsening during treatment with fluoxetine in major depressive disorder: prevalence and implications
Cusin C, Fava M, Amsterdam JD, Quitkin FM,
Reimherr FW, Beasley CM Jr, Rosenbaum JF, Perlis RH.
Depression Clinical and Research Program,
Massachusetts General Hospital,
Harvard Medical School,
Boston, MA 02114, USA.
J Clin Psychiatry. 2007 Jan;68(1):52-7.


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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