Psychological Medicine

Original Articles

Residual symptoms after remission of major depressive disorder with citalopram and risk of relapse: a STAR*D report

A. A. Nierenberga1 c1, M. M. Husaina2, M. H. Trivedia2, M. Favaa1, D. Wardena2, S. R. Wisniewskia3, S. Miyaharaa3 and A. J. Rusha4

a1 Depression Clinical and Research Program, Massachusetts General Hospital, Boston, MA, USA

a2 The University of Texas Southwestern Medical Center, Department of Psychiatry, Dallas, TX, USA

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

a4 The University of Texas Southwestern Medical Center, Departments of Clinical Sciences and Psychiatry, Dallas, TX, USA


Background Many patients with major depressive disorder (MDD) who experience full symptomatic remission after antidepressant treatment still have residual depressive symptoms. We describe the types and frequency of residual depressive symptoms and their relationship to subsequent depressive relapse after treatment with citalopram in the Sequenced Treatment Alternatives to Relieve Depression (STAR*D) trial.

Method Participants in primary (n=18) and psychiatric (n=23) practice settings were openly treated with citalopram using measurement-based care for up to 14 weeks and follow-up for up to 1 year. We assessed 943 (32.8% of 2876) participants who met criteria for remission to determine the proportions with individual residual symptoms and any of the nine DSM-IV criterion symptom domains to define a major depressive episode. At each visit, the 16-item Quick Inventory of Depressive Symptomatology, Self-Report (QIDS-SR16) and the self-report Frequency, Intensity, and Burden of Side Effects Rating (FIBSER) scale were used to assessed depressive symptoms and side-effects respectively.

Results More than 90% of remitters had at least one residual depressive symptom (median=3). The most common were weight increase (71.3%) and mid-nocturnal insomnia (54.9%). The most common residual symptom domains were sleep disturbance (71.7%) and appetite/weight disturbance (35.9%). Those who remitted before 6 weeks had fewer residual symptoms at study exit than did later remitters. Residual sleep disturbance did not predict relapse during follow-up. Having a greater number of residual symptom domains was associated with a higher probability of relapse.

Conclusions Patients with remission of MDD after treatment with citalopram continue to experience selected residual depressive symptoms, which increase the risk of relapse.

(Received December 01 2008)

(Revised April 07 2009)

(Accepted April 10 2009)

(Online publication May 22 2009)


c1 Address for correspondence: A. A. Nierenberg, M.D., Massachusetts General Hospital, Suite 580, 50 Staniford Street, Boston, MA 02114, USA. (Email: