ORIGINAL ARTICLE The Role of Cognitive-Behavioral Therapy and Fluoxetine in Prevention of Recurrence of Major Depressive Disorder Timothy J. Petersen Æ Joel A. Pava Æ Jacqueline Buchin Æ John D. Matthews Æ George I. Papakostas Æ Andrew A. Nierenberg Æ Avram J. Holmes Æ Ryan Bogdan Æ Lesley M. Graves Æ Rebecca M. Harley Æ Maurizio Fava Ó Springer Science+Business Media, LLC 2007 Abstract This study evaluated the role of cognitive-behavioral therapy (CBT) and fluoxetine in preventing recurrence of a depressive episode during maintenance phase treatment for patients with remitted major depressive disorder (MDD). Patients (n = 52) completed open acute fluoxetine treatment and sustained remission during a 28-week randomized continuation treatment (CBT + fluoxetine vs. fluoxetine only). They were assigned to one of four main- tenance treatments: CBT + fluoxetine, CBT + placebo, fluoxetine only, and placebo only. There were no statistically significant differences in MDD recurrence between maintenance treatments, but continued antidepressant treatment (with or without CBT) provided an 18–21% lower MDD recurrence rate than placebo. These findings are consistent with those of recent antidepressant studies of chronic and recurrent MDD populations. Although sample sizes were small, CBT did not significantly lower rates of MDD recurrence. Keywords CBT Á Fluoxetine Á Recurrence Á Relapse Á Major Depressive Disorder Á Treatment Á Prevention Major depressive disorder (MDD) is a highly recurrent, often chronic illness (Fava and Kaji 1994). Even following successful acute phase treatment, patients remain at risk for relapse of the index depressive episode or the emergence of a new episode (recurrence). Patients not T. J. Petersen (&) Depression Clinical and Research Program, Department of Psychiatry, Massachusetts General Hospital, 15 Parkman Street, WAC 812, Boston, MA 02114, USA e-mail: tpetersen@partners.org J. A. Pava Á J. Buchin Á J. D. Matthews Á A. A. Nierenberg Á A. J. Holmes Á R. Bogdan Á L. M. Graves Á R. M. Harley Á M. Fava Department of Psychology, Harvard University, Cambridge, MA 02138, USA G. I. Papakostas Department of Psychiatry, Massachusetts General Hospital, 50 Staniford Street, Suite 401, Boston, MA 02114, USA 123 Cogn Ther Res DOI 10.1007/s10608-007-9166-6