5-HT2c agonist, lorcaserin, reduces aggressive responding in intermittent explosive disorder: A pilot study

Rationale Impulsive aggressive behavior is associated with reduced central function of serotonin (5-HT). Although selective serotonin reuptake inhibitors can reduce such behaviors, many with history of impulsive aggression do not respond adequately to selective serotonin reuptake inhibitors and may require treatment with a direct 5-HT agonist. Objectives To test the hypothesis that pretreatment with the selective 5-HT2c agonist, lorcaserin, can reduce aggressive responding in impulsively aggressive individuals. Methods Ten male and female adults were given lorcaserin (20 mg), or a matching placebo, in random order, on 2 days separated by at least 1 week. The Taylor aggression paradigm was used to assess aggressive responding, which was represented by mean shock setting administered to an opponent and by frequency of setting high and extreme shock levels to the opponent. Results Compared with placebo, lorcaserin attenuated provoked, but not unprovoked, aggression during the Taylor aggression paradigm. This was manifest by reduction in the frequency of selecting high and extreme levels of shock against the opponent. Conclusion Lorcaserin may possess anti-aggressive properties that could prove useful in the treatment of impulsive aggressive behavior in human subjects. These data, thus, provide a rationale for a follow-up randomized clinical trial of lorcaserin in individuals with prominent histories of impulsive aggressive behavior.