EFFECTS OF SEROTONIN REUPTAKE INHIBITORS ON AGGRESSIVE-BEHAVIOR IN PSYCHIATRICALLY HOSPITALIZED ADOLESCENTS - RESULTS OF AN OPEN TRIAL

Low concentations of the neurotransmitter serotonin and its 5-hydroxyi ndoleacetic acid metabolite in the central nervous system have been as sociated with increased aggressive behavior in animals and humans. Con trolled clinical trials of serotonin agonists in depressed adults have suggested that aggressive behavior is less likely during treatment wi th these medications than with placebo, but there have been no previou s studies of selective serotonin reuptake inhibitors (SSRIs) and aggre ssion in children. We prospectively followed the course of aggressive behavior in 19 psychiatrically hospitalized adolescents (not selected for aggressiveness) who received open clinical trials of fluoxetine, p aroxetine, or sertraline. The patients received standard doses (equiva lent to fluoxetine 10-40 mg daily) for a minimum of 5 weeks. The start ing dose was 15 +/- 5 mg, and dosages were raised at a mean rate of 5 mg every 4 days up to a mean dose of 25 +/- 10 mg daily. Results from trials of the three SSRIs were clustered because the sample sizes were not sufficient for separate analyses. Overall, there were no statisti cally meaningful improvements in the level of aggressive behavior, as measured on a modified version of the Overt Aggression Scale, over the course of these patients' SSRI trials. Symptoms of physical aggressio n toward others or self were manifest in 12 of the 19 patients while o n SSRIs. Of the 19 patients, 13 were assessed both on and off SSRIs: v erbal aggression (p = 0.04), physical aggression toward objects (p = 0 .05), and physical aggression toward self (p < 0.02) occurred signific antly more frequently on SSRIs than off; no increase was observed in p hysical aggression toward others. Patients with the highest baseline a ggressivity scores did not show greater improvement during SSRI treatm ent. Further research is warranted, particularly to explore whether SS RIs may have therapeutic effects on aggression at higher (or lower) do ses than were administered in this open trial.