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Original Research

Do Suicidal Thoughts or Behaviors Recur During a Second Antidepressant Treatment Trial?

Roy H. Perlis, MD, MSc; Rudolf Uher, MD, PhD; Nader Perroud, MD; and Maurizio Fava, MD

Published: September 18, 2012

Article Abstract

Objective: A subset of patients undergoing initial antidepressant treatment experience worsening of symptoms, including thoughts of suicide or suicidal behavior. The present study explores whether this subset of patients is also more likely to experience recurrence or worsening of these symptoms during a second treatment trial with a different antidepressant.

Method: We examined data collected between July 2001 and September 2006 from the Sequenced Treatment Alternatives to Relieve Depression (STAR*D) study, a multicenter effectiveness study of outpatients with major depressive disorder diagnosed by a DSM-IV checklist. In that study, subjects who did not remit with citalopram treatment were randomized among next-step treatment options. The main outcome measure for this post hoc analysis, presence of suicidal thoughts and behaviors, was assessed using the suicide item on the 16-item Quick Inventory of Depressive Symptomatology—Self-Rated. Logistic regression was used to examine association between emergence or worsening of these symptoms with the first-step (level 1) citalopram treatment and emergence or worsening with next-step (level 2) pharmacologic or psychosocial treatment, including augmentation with bupropion or buspirone; switch to sertraline, venlafaxine, or bupropion; or addition of or switch to cognitive therapy.

Results: Of 1,240 subjects entering level 2 with a score less than 3 on the suicide item, 102 (8.2%) experienced emergence or worsening of suicidal thoughts or behaviors. Emergence or worsening at level 1 was strongly associated with reemergence or worsening at level 2 (crude OR=4.00 [95% CI, 2.45-6.51], adjusted OR=2.95 [95% CI, 1.76-4.96]). Overall magnitude of risk was similar among next-step pharmacologic augmentation versus switching.

Conclusions: These results suggest that individuals who experience emergence or worsening of suicidal thoughts or behaviors with one antidepressant treatment may warrant closer follow-up during the next-step treatment, as these symptoms may recur regardless of which modality is selected.

J Clin Psychiatry

Submitted: March 13, 2012; accepted June 18, 2012.

Online ahead of print: September 18, 2012 (doi:10.4088/JCP.12m07777).

Corresponding author: Roy H. Perlis, MD, MSc, Center for Experimental Drugs and Diagnostics, Massachusetts General Hospital, 185 Cambridge St, 6th Floor, Boston, MA 02114 (

Volume: 73

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