Activation Syndrome in Patients Diagnosed With Major Depressive Disorder for the First Time: The Role of Past...

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.

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.

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.

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.