It has been previously purported that higher relative affinity to the dopamine D4 receptor compared to D2 (i.e., D4/D2 affinity ratio > 1) may underlie unique antiaggression potency. Asenapine is a newer antipsychotic that also has D4/D2 affinity ratio > 1. It has demonstrated efficacy in reducing acute agitation in a placebo-controlled study. We performed a prospective naturalistic, pilot, proof of concept study on an inpatient psychiatric unit. Among patients with aggression at time of admission (≥ 12 on Refined Aggression Questionnaire [RAQ], or ≥ 2 on Modified Overt Aggression Scale [MOAS]), asenapine treatment was associated with a significant reduction in total aggression as measured by the MOAS (-14.7 ± 11.59 vs. -5.4 ± 10.12, P = 0.045), and particularly physical aggression (-8.0 ± 5.06 vs. -0.78 ± 2.40, P < 0.0001) compared to treatment that did not include asenapine. These data suggest that asenapine may be useful in the targeted treatment of aggression, and provide some support for the D4/D2 affinity ratio hypothesis.
Keywords: aggression; asenapine; dopamine receptors; physical aggression; treatment; violence.