Incidence and predictors of activation syndrome induced by antidepressants

Activation syndrome is a side effect of antidepressants that is thought to carry a potentially increased risk of suicide. However, the incidence of activation syndrome has not been fully investigated and little has been reported on its predictors. The aim of this study was to survey the incidence of activation syndrome and clarify its predictors in a natural clinical setting.

Among 2,521 new outpatients visiting between August 2003 and March 2005, we retrospectively surveyed the case records of 729 patients who had not taken any antidepressants during the 1 month before presentation and were prescribed antidepressants for 3 months after the initial visit. Patients were classified as developing activation syndrome if they experienced any symptom of anxiety, agitation, panic attacks, insomnia, irritability, hostility, aggressiveness, impulsivity, akathisia, hypomania, and mania during the first 3 months.

Of the 729 patients, 31 (4.3%) developed activation syndrome. The incidence was not significantly related to gender, age, class of antidepressant, combined use of benzodiazepine, or DSM-IV-TR diagnosis except for personality disorder. Diagnosis of personality disorder was significantly associated with the induction of activation syndrome (odds ratio=4.20, P=0.002).

This study suggests that diagnosis of personality disorder may be a clinical predictor of activation syndrome.