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Eur Arch Psychiatry Clin Neurosci. 2010 Mar;260(2):145-50. doi: 10.1007/s00406-009-0031-3. Epub 2009 Jul 2.

Type of residual symptom and risk of relapse during the continuation/maintenance phase treatment of major depressive disorder with the selective serotonin reuptake inhibitor fluoxetine.

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Department of Psychiatry, Depression Clinical and Research Program at Massachusetts General Hospital, Harvard Medical School, 15 Parkman Street, Boston, MA 02114, USA.


Relapse of major depressive disorder (MDD) is a common clinical problem. Identifying relapse predictors could lead to strategies that reduce relapse risk. This study is designed to determine whether residual symptoms predict relapse risk during the continuation/maintenance treatment of MDD. 570 MDD patients received open-label fluoxetine for 12 weeks. Under double blind conditions, 262 patients who responded by week 12 were randomly assigned to continue fluoxetine or switch to placebo for 52 weeks or until relapse. Residual symptoms were measured using the Symptom Checklist-90 and the Symptom Questionnaire. The relationship between residual symptom severity and relapse risk was assessed. Without adjusting for overall residual symptom severity, a greater severity of residual obsessive-compulsive and phobic anxiety symptoms predicted greater relapse risk. After adjusting for overall residual symptom severity, only severity of phobic anxiety symptoms predicted relapse risk. The predictive value of phobic anxiety symptoms with respect to relapse risk was independent of treatment assignment. The results indicated that there may be a specific pattern of residual symptoms associated with depressive relapse during antidepressant continuation/maintenance, which is unrelated to treatment assignment. Future studies are needed to further explore the relationship between residual symptoms and relapse risk in MDD.


(1) It is important to treat residual symptoms among antidepressant responders/remitters in order to decrease relapse risk. (2) Clinicians should target residual phobic anxiety symptoms in order to decrease relapse risk. (3) Clinicians should target residual obsessive-compulsive symptoms in order to decrease relapse risk.


(1) limited generalizability due to inclusion/exclusion criteria; (2) lack of active comparator treatment group; (3) post hoc analysis.

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