Objective: The aim of this study was to examine the prevalence of activation cluster adverse events (AC-AEs) in youths treated with the selective serotonin reuptake inhibitor (SSRI) fluvoxamine for anxiety and the relationship of AC-AEs to SSRI blood levels.
Methods: Data from the Research Units on Pediatric Psychopharmacology (RUPP) Anxiety Study were examined for 45 youths (22 active fluvoxamine, 23 placebo) treated for Diagnostic and Statistical Manual for Mental Disorders, 4(th) edition (DSM-IV) anxiety disorders at the Johns Hopkins University site with an 8-week forced-flexible titration schedule. As part of the double-blind placebo-controlled trial, AC-AEs were recorded by clinicians at weekly patient visits. AC-AEs were defined as hyperactivity, activation, and disinhibition. Demographic characteristics, daily doses, and week-8 blood levels were examined in relation to the presence of AC-AEs. The prevalence of AC-AE and time to first event were established for those who experienced this side effect.
Results: AC-AEs were found in 10 of 22 participants (45%) receiving fluvoxamine and only 1 of 23 in the placebo group (4%). The onset of AC-AEs occurred from week 1 to week 8, with the majority occurring at or before week 4. The mean fluvoxamine blood level at week 8 in subjects with AC-AEs was higher than in subjects without AC-AEs (n = 16, t = -2.61, p = 0.04). Neither the age of the participants nor family history of bipolar or anxiety disorder differed between those who did and did not develop an AC-AE.
Conclusions: AC-AEs were common side effects of fluvoxamine, often appeared during the first 8 weeks of treatment, and were associated with higher fluvoxamine blood levels. Close monitoring for AC-AEs, not only when initiating SSRI treatment but also throughout dose titration, is recommended for early identification of activation.