Asenapine for aggressive behaviours in psychiatric disorders: a systematic review of efficacy and real-world effectiveness

Background: Clinical decision-making for the pharmacological treatment of aggressive behaviour in psychiatry remains challenging. Asenapine, a second-generation antipsychotic with a higher affinity for dopamine D4 than for D2 receptors, may become a treatment option, although this remains to be demonstrated. Methods: A systematic search was conducted across biomedical databases according to PRISMA Reporting Items for Systematic Review. We aimed to examine the efficacy and effectiveness of asenapine in the management of aggressive behaviours including psychomotor agitation, hostility, irritability, anger, impulsivity, self-harm, behavioural disinhibition, as well as physical and verbal aggression, across psychiatric disorders. Results: Of the 12 studies included, four reported asenapine’s efficacy in aggressive behaviours compared to placebo, and five described the effectiveness in uncontrolled settings. Three studies found no advantages over olanzapine. Major evidence supports asenapine’s efficacy in reducing psychomotor agitation and hostility, with benefits independent of its anti-manic and antipsychotic effects. Conclusion: Asenapine may be a viable option for the treatment of psychomotor agitation and hostility, although more head-to-head trials are needed to clarify its efficacy relative to other antipsychotics. Since the evidence of efficacy in other aggressive domains and diagnoses is still limited, clinicians should primarily consider the tolerability profile to guide their prescription.