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Proposed DSM-5 mixed features are associated with greater likelihood of remission in out-patients with major depressive disorder

Published online by Cambridge University Press:  15 March 2012

R. H. Perlis*
Department of Psychiatry, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA
C. Cusin
Department of Psychiatry, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA
M. Fava
Department of Psychiatry, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA
*Address for correspondence: R. H. Perlis, M.D., Massachusetts General Hospital, Center for Experimental Drugs and Diagnostics, 185 Cambridge Street, Boston, MA 02114, USA. (Email:



Draft DSM-5 criteria for a mixed major depressive episode have been proposed, but their predictive validity has not yet been established. We hypothesized that such symptoms would be associated with poorer antidepressant treatment outcomes.


We examined outcomes among individuals with major depressive disorder participating in the Sequenced Treatment Alternatives to Relieve Depression (STAR*D) study, an effectiveness study conducted at primary and specialty care centers in the USA. Mixed features were derived from the six self-report items of the mania subscale of the Psychiatric Diagnosis Screening Questionnaire. Primary analyses examined the association between the presence of at least two of these in the 6 months before study entry, and remission across up to four sequential treatment trials, as well as adverse outcomes.


Of the 2397 subjects with a major depressive episode of at least 6 months' duration, 449 (18.7%) reported at least two mixed symptoms. The presence of such symptoms was associated with a greater likelihood of remission across up to four sequential treatments, which persisted after adjustment for potential confounding clinical and demographic variables (adjusted hazard ratio 1.16, 95% confidence interval 1.03–1.28). Two individual items, expansive mood and cheerfulness, were strongly associated with a greater likelihood of remission.


Proposed DSM-5 mixed state features were associated with a greater rather than a lesser likelihood of remission. While unexpected, this result suggests the potential utility of further investigation of depressive mixed states in major depression.

Original Articles
Copyright © Cambridge University Press 2012 

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