The International Journal of Neuropsychopharmacology

Research Article

What predicts attrition in second step medication treatments for depression?: a STAR*D Report

Diane Wardena1 c1, A. John Rusha1a2, Stephen R. Wisniewskia3, Ira M. Lessera4, Susan G. Kornsteina5, G. K. Balasubramania3, Michael E. Thasea6, Sheldon H. Preskorna7, Andrew A. Nierenberga8, Elizabeth A. Younga9, Kathy Shores-Wilsona1 and Madhukar H. Trivedia1

a1 Department of Psychiatry, The University of Texas Southwestern Medical Center at Dallas, Dallas, TX, USA

a2 Department of Clinical Sciences, The University of Texas Southwestern Medical Center at Dallas, Dallas, TX, USA

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

a4 Department of Psychiatry and Los Angeles Biomedical Research Institute at Harbor – UCLA Medical Center, Torrance, CA, USA

a5 Department of Psychiatry, Virginia Commonwealth University, Richmond, VA, USA

a6 Department of Psychiatry, University of Pennsylvania, Philadelphia, PA, USA

a7 Department of Psychiatry and Behavioral Sciences, University of Kansas School of Medicine, Wichita, KS, USA

a8 Clinical Psychopharmacology Unit, Massachusetts General Hospital, Boston, MA, USA

a9 Department of Psychiatry and Mental Health Research Institute, University of Michigan, Ann Arbor, MI, USA


Attrition rates are high during treatment for major depressive disorder (MDD), and patients who drop out are less likely to reach remission. This report evaluates the incidence, timing, and predictors of attrition during second-step medication treatment. Outpatients in the multisite Sequenced Treatment Alternatives to Relieve Depression (STAR*D) study receiving a medication augmentation (n=563) or medication switch (n=723) for non-psychotic MDD after an unsatisfactory outcome with citalopram were evaluated to determine attrition rates and pretreatment sociodemographic or clinical predictors of attrition. Twenty percent of participants receiving a medication augmentation and 27% receiving a medication switch dropped out before 12 wk in the second treatment step. Remission rates were lower for dropouts [7% vs. 43% (medication augmentation); 12% vs. 31% (medication switch)]. For medication augmentation, Black and other non-Caucasian races, Hispanic ethnicity, younger age, family history of drug abuse, concurrent drug abuse, sociodemographic disadvantage, less symptom improvement with initial citalopram treatment, and greater symptom severity when beginning augmentation were associated with attrition. For medication switch, Black and other non-Caucasian races, younger age, more melancholic features, and lower exit doses but more severe side-effects with citalopram treatment were associated with attrition. Minority status, younger age, and greater difficulty with the first treatment step are risk factors for attrition in the second treatment step. Focus on patients with attrition risk factors for medication augmentation or switch strategies may enhance retention and improve outcomes.

(Received April 04 2008)

(Reviewed May 04 2008)

(Revised May 15 2008)

(Accepted May 24 2008)

(Online publication July 09 2008)


c1 Address for correspondence: D. Warden, Ph.D., M.B.A., Department of Psychiatry, The University of Texas Southwestern Medical Center at Dallas, 5323 Harry Hines Blvd., Dallas, TX 75390-9119. Tel.: +1-214-648-4614 Fax: +1-214-648-0168 E-mail:


Portions of this paper were presented in poster form at the International Society for Affective Disorders (ISAD), 4th Biennial Conference, Capetown, South Africa, March 2008.