The International Journal of Neuropsychopharmacology

Thematic Section: New Aspects in the Treatment of Affective Disorders

Do atypical features affect outcome in depressed outpatients treated with citalopram?

Jonathan W. Stewarta1 c1, Patrick J. McGratha1, Maurizio Favaa2, Stephen R. Wisniewskia3, Sidney Zisooka4, Ian Cooka5, Andrew A. Nierenberga2, Madhukar H. Trivedia6, G. K. Balasubramania3, Diane Wardena6, Ira Lessera5 and A. John Rusha7

a1 New York State Psychiatric Institute and Department of Psychiatry, the College of Physicians and Surgeons of Columbia University, New York, NY, USA

a2 Clinical Psychopharmacology Unit, Massachusetts General Hospital, Boston, MA, USA

a3 Epidemiology Data Center, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, PA, USA

a4 Department of Psychiatry, University of California, San Diego, and San Diego VA Medical Center, San Diego, CA, USA

a5 Department of Psychiatry, University of California, Los Angeles, CA, USA

a6 Department of Psychiatry, University of Texas, Southwestern Medical Center, Dallas, TX, USA

a7 Duke-National University of Singapore, Singapore


Depressed patients with atypical features have an earlier onset of depression, a more chronic course of illness, several distinctive biological and familial features, and a different treatment response than those without atypical features. The efficacy and tolerability of selective serotonin reuptake inhibitors (SSRIs) have not been fully evaluated in depression with atypical features. This report evaluates data from the Sequenced Treatment Alternatives to Relieve Depression (STAR*D) study to determine whether depressed outpatients with and without atypical features respond differently to the SSRI citalopram. Treatment-seeking participants with non-psychotic major depressive disorder were recruited from primary- and psychiatric-care settings. The presence/absence of atypical features was approximated using baseline ratings on the 30-item Inventory of Depressive Symptomatology – Clinician-rated. Following baseline assessments, participants received citalopram up to 60 mg/d for up to 14 wk. Baseline sociodemographic and clinical characteristics, and treatment outcomes, were compared between participants with and without atypical features. Of the 2876 evaluable STAR*D participants, 541 (19%) had atypical features. Participants with atypical features were significantly more likely to be female, younger, unemployed, have greater physical impairment, a younger age of depression onset, a longer index episode, greater depressive severity, and more concurrent anxiety diagnoses. Those with atypical features had significantly lower remission rates, although this difference was no longer present after adjustment for baseline differences. Depressed patients with atypical features are less likely to remit with citalopram than those without atypical features. This finding is probably due to differences in baseline characteristics other than atypical symptom features.

(Received October 27 2008)

(Reviewed November 30 2008)

(Revised January 27 2009)

(Accepted February 03 2009)

(Online publication April 03 2009)


c1 Address for correspondence: J. W. Stewart, M.D., 1051 Riverside Drive, New York, NY 10032, USA. Tel.: 212-543-5734 Fax: 212-543-5326 Email: