Mixed depression: Clinical features and predictors of its onset associated with antidepressant use

Gabriele Sani, Flavia Napoletano, Paul A. Vöhringer, Matthew Sullivan, Alessio Simonetti, Athanasios Koukopoulos, Emanuela Danese, Paolo Girardi, Nassir Ghaemi

Research output: Contribution to journalArticle


Background: Mixed depression (MxD) is narrowly defined in the DSM-IV and somewhat broader in the DSM-5, although both exclude psychomotor agitation as a diagnostic criterion. This article proposes a clinical description for defining MxD, which emphasizes psychomotor excitation. Methods: Two hundred and nineteen consecutive outpatients were diagnosed with an MxD episode using criteria proposed by Koukopoulos et al. [Acta Psychiatr Scand 2007;115(suppl 433):50-57]; we here report their clinical features and antidepressant-related effects. Results: The most frequent MxD symptoms were: psychic agitation or inner tension (97%), absence of retardation (82%), dramatic description of suffering or weeping spells (53%), talkativeness (49%), and racing or crowded thoughts (48%). MxD was associated with antidepressants in 50.7% of patients, with similar frequency for tricyclic antidepressants (45%) versus selective serotonin reuptake inhibitors (38.5%). Positive predictors of antidepressant-associated MxD were bipolar disorder type II diagnosis, higher index depression severity, and higher age at index episode. Antipsychotic or no treatment was protective against antidepressant-associated MxD. Conclusions: MxD, defined as depression with excitatory symptoms, can be clinically identified, is common, occurs in both unipolar depression and bipolar disorder, and is frequently associated with antidepressant use. If replicated, this view of MxD could be considered a valid alternative to the DSM-5 criteria for depression with mixed features.

Original languageEnglish
Pages (from-to)213-221
Number of pages9
JournalPsychotherapy and Psychosomatics
Issue number4
Publication statusPublished - 2014



  • Antidepressants
  • Bipolar disorder
  • Clinical predictors
  • Major depressive disorder
  • Mixed depression

ASJC Scopus subject areas

  • Clinical Psychology
  • Applied Psychology
  • Psychiatry and Mental health
  • Medicine(all)

Cite this

Sani, G., Napoletano, F., Vöhringer, P. A., Sullivan, M., Simonetti, A., Koukopoulos, A., Danese, E., Girardi, P., & Ghaemi, N. (2014). Mixed depression: Clinical features and predictors of its onset associated with antidepressant use. Psychotherapy and Psychosomatics, 83(4), 213-221. https://doi.org/10.1159/000358808