Research report Predominant previous polarity as an outcome predictor in a controlled treatment trial for depression in bipolar I disorder patients E. Vieta a,b, ⁎, M. Berk c , W. Wang d , F. Colom a,d , M. Tohen b,e , R.J. Baldessarini b a Bipolar Disorders Program, University of Barcelona Hospital Clinic, Institut d'Investigacions Biomédiques Agustí Pi Sunyer, CIBER-SAM, Barcelona, Spain b Department of Psychiatry & Neuroscience Program, Harvard Medical School; International Consortium for Bipolar Disorders Research, McLean Hospital, Boston, Massachusetts, USA c Department of Clinical and Biomedical Sciences, University of Melbourne; The Mental Health Research Institute and Orygen Research Center, Melbourne, Australia d Department of Psychiatry, Univerity of Oxford, United Kingdom e Lilly Research Laboratories, Indianapolis, Indiana, USA article info abstract Article history: Received 15 September 2008 Received in revised form 25 February 2009 Accepted 26 February 2009 Available online 26 March 2009 Introduction: We hypothesized that predominant episode-polarity would predict response to treatment of depressive episodes in bipolar I disorder (BPD) patients with treatment in a placebo-controlled trial, in the sense that patients with manic predominant polarity (PM) would respond better than patients with depressive predominant polarity (PD). Method: This post-hoc analysis of a published trial examined outcomes of 788 depressed (MADRS score ≥20) adult BPD patients with baseline and follow-up assessments, according to their predominant polarity based on previous recurrences of mania-hypomania vs. depression in ≥2:1 excess. Patients (total=833) were randomized to an 8-week trial of treatment with placebo (n = 377), olanzapine (5–20 mg/day; n = 370), or olanzapine/fluoxetine combination (OFC; 6/25, 6/50, or 12/50 mg/day; n =86). Treatment response was based on improvement in Clinical Global Impression of depression severity (CGI-D). We analyzed for associations of this outcome with predominant lifetime illness-polarity, based on retrospective SCID-based assessment of individual clinical history. Results: Predominant polarity could be demonstrated in 367/788 patients (46.6%), showing a 2.7-fold excess of predominant depressive over manic past-illnesses (34.1%/12.4%), with similar distribution by sex and among treatment-arms. Moreover, based on least-square change in CGI- D severity (based on a mixed model of repeated measures [MMRM]), predominant polarity has different impact in the treatment outcome for each gender. Men with predominantly manic polarity had statistically significant better improvement than men with predominantly depressive polarity. Such difference was not observed in the female population. Other outcome measures yielded similar conclusions. Conclusions: Predominant previous depressive N manic episodes selectively yielded poorer responses of BPD to treatment for acute BP depression, particularly in men. © 2009 Elsevier B.V. All rights reserved. Keywords: Bipolar disorder Course of illness Depression Mania Polarity Treatment response Predominance of episode polarity over the course of bipolar disorder (BPD), as well as the polarity of initial or index (most recent) episode, have all been associated with treatment response and outcome of later acute episodes. For example, initial depressive or mixed-states predict an excess of similar morbidity during long-term follow-up (Baldessarini et al., 2004); the presenting illness polarity of an index episode of BPD can predict both overall long-term treatment response (Faedda et al., 1991; Daban et al., 2006; Salvatore et al., 2006) as well as the polarity of a first recurrence during long-term treatment (Calabrese et al., 2004); and predominant depression appears to be an unfavorable factor for long-term treatment response, Journal of Affective Disorders 119 (2009) 22–27 ⁎ Corresponding author. Bipolar Disorders Program, Clinical Institute of Neuroscience, Hospital Clinic, University of Barcelona, Villarroel 170. 08036 Barcelona, Spain. Tel.: +34 93 227 5401; fax: +34 93 227 9876. E-mail addresses: evieta@clinic.ub.es, evieta@mclean.harvard.edu (E. Vieta). 0165-0327/$ – see front matter © 2009 Elsevier B.V. All rights reserved. doi:10.1016/j.jad.2009.02.028 Contents lists available at ScienceDirect Journal of Affective Disorders journal homepage: www.elsevier.com/locate/jad