title: Timing of clinical improvement and symptom resolution in the treatment of major depressive disorder.
abstract: The goal of the present work is to assess for the relationship between the timing of clinical improvement and the resolution of depressive symptoms in Major Depressive Disorder (MDD). 182 MDD outpatients (40.5+/-9.7 years; 53.8% female) who responded following an 8-week, 20 mg, open trial of fluoxetine were included in the analysis. The symptoms questionnaire (SQ) and Beck hopelessness scale (BHS) were also administered to 83 and 153 of these patients, respectively. Onset of clinical improvement was defined as a 30% decrease in 17-item Hamilton depression scale (HDRS-17) scores. Controlling for baseline symptom severity, we then assessed for the relationship between the timing of clinical improvement and depressive symptom at endpoint. Earlier clinical improvement in responders predicted lower HDRS-17, BHS, SQ-depression, SQ-anxiety, but not SQ-somatic symptom or SQ-anger/hostility scores at week 8. This was true regardless of whether improvement was defined as a continuous measure (30% decrease in symptom severity), as a dichotomous measure (clinical response occurring in the first two weeks of treatment). In conclusion, earlier clinical improvement with fluoxetine treatment is predictive of greater symptom resolution at endpoint. Further studies exploring the impact of various treatment modalities and placebo on the timing of clinical improvement and symptom resolution in MDD are warranted.
authors.affiliation: Depression Clinical and Research Program, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA. gpapakostas@partners.org
authors.forename: George I
authors.initials: GI
authors.lastname: Papakostas
authors.forename: Timothy
authors.initials: T
authors.lastname: Petersen
authors.forename: Katherine G
authors.initials: KG
authors.lastname: Sklarsky
authors.forename: Andrew A
authors.initials: AA
authors.lastname: Nierenberg
authors.forename: Jonathan E
authors.initials: JE
authors.lastname: Alpert
authors.forename: Maurizio
authors.initials: M
authors.lastname: Fava
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000786:Anger; D001008:Anxiety Disorders / Q000175:diagnosis / Q000523:psychology; D003865:Major Depressive Disorder / Q000175:diagnosis / Q000188:drug therapy* / Q000523:psychology*; D039721:Diagnostic and Statistical Manual of Mental Disorders; D005260:Female; D005473:Fluoxetine / Q000627:therapeutic use*; D006791:Hostility; D006801:Humans; D008297:Male; D008875:Middle Aged; D017367:Selective Serotonin Reuptake Inhibitors / Q000627:therapeutic use*; D012720:Severity of Illness Index; D011795:Surveys and Questionnaires; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D005473:Fluoxetine; D017367:Selective Serotonin Reuptake Inhibitors