Lorcaserin shows therapeutic potential in patients with impulsive aggressive behaviour

The 5-HT_2c receptor agonist lorcaserin has the potential to be repurposed for the treatment of impulsive aggression in humans, as shown in a pilot study.

Ten male and female adults with impulsive aggressive behaviour were randomly assigned to receive lorcaserin 20 mg or a matching placebo for 2 days separated by at least a 7-day washout. Researchers evaluated aggressive responding using the Taylor aggression paradigm, where patients competed against a fictitious opponent in a reaction time game during which electric shock was administered and received.

All participants had high aggression scores on the Life History of Aggression assessment (mean, 20.3) and the Buss-Perry Aggression questionnaire (mean, 47.6) relative to mean scores of 6.4 and 30.7, respectively, in nonaggressive participants reported in the literature.

Compared with placebo, lorcaserin mitigated provoked, but not unprovoked, aggression during the Taylor aggression paradigm. This was demonstrated by significant reductions in the mean frequency of selecting “high/extreme” shock levels against the opponent (7.30 with placebo vs 2.50 with the active drug; p=0.030).

The findings provide a rationale to conduct a double-blind clinical trial of lorcaserin in impulsively aggressive individuals to establish the potential antiaggressive effect of the drug, according to the researchers.

“[T]hat lorcaserin may have antiaggressive properties is consistent with the serotonin hypothesis of aggression that posits that agents that increase serotonergic activity will reduce impulsively aggressive behaviour,” they explained.  (Coccaro et al., 1989; Coccaro, Lee, & Kavoussi, 2010).

However, the researchers also pointed out that “as a receptor agonist, lorcaserin may work when selective serotonin reuptake inhibitors are not effective, especially in cases where postsynaptic serotonin (eg, 5-HT_2c) receptors are highly downregulated.”