Activation Syndrome in Patients Diagnosed With Major Depressive Disorder for the First Time

GÖKÇEN O., KARATAŞ K. S., AKKUŞ M., DÖNMEZ F., Konak M. A.

JOURNAL OF NERVOUS AND MENTAL DISEASE, vol.214, no.3, pp.59-67, 2026 (SCI-Expanded, SSCI, Scopus)

  • Publication Type: Article / Article
  • Volume: 214 Issue: 3
  • Publication Date: 2026
  • Doi Number: 10.1097/nmd.0000000000001871
  • Journal Name: JOURNAL OF NERVOUS AND MENTAL DISEASE
  • Journal Indexes: Science Citation Index Expanded (SCI-EXPANDED), Social Sciences Citation Index (SSCI), Scopus, Abstracts in Social Gerontology, ATLA Religion Database, BIOSIS, CINAHL, Educational research abstracts (ERA), EMBASE, MEDLINE, MLA - Modern Language Association Database, Psycinfo, MLA International Bibliography, Academic Search Ultimate (EBSCO), Health Research Premium Collection (ProQuest)
  • Page Numbers: pp.59-67
  • Istanbul University Affiliated: No

Abstract

Aim:Activation syndrome, a possible consequence of antidepressant treatment, has been linked to suicidal ideation, yet its definition remains debated. This study investigated the frequency and risk factors of activation syndrome in patients with first-episode major depressive disorder.Methods:Two hundred six patients were assessed at baseline, week 2, and week 4. Baseline measures included the Hypomania-Checklist-32, the Temperament Evaluation of Memphis, Pisa, Paris, and San Diego-autoquestionnaire, and evaluations of anxious distress, mixed features, and atypical depression. Follow-up interviews assessed activation syndrome.Results:Activation Syndrome occurred in 33% (n = 68). It was associated with younger age, atypical depression, higher Hypomania-Checklist-32 scores, anxious distress, cyclothymic/irritable temperaments, and suicidal ideation. Logistic regression showed past hypomania and atypical depression as significant predictors. Associations remained after excluding mania/hypomania cases.Conclusions:In first-episode major depressive disorder, past hypomania symptoms and atypical depression increase activation syndrome risk, highlighting the need for close monitoring given implications for bipolarity and suicidality.