Specific Anti-hostility Effects of Atypical Antipsychotics in Persons with Schizophrenia: From Clozapine to Cariprazine.

LEARNING OBJECTIVE: After participating in this activity, learners should be better able to:• Evaluate the anti-hostility effects of available atypical antipsychotic agents.

ABSTRACT: In addition to hallucinations and delusions, persons with schizophrenia may exhibit hostility. In clinical trials of antipsychotics, hostility is routinely measured as part of rating scales such as the Brief Psychiatric Rating Scale or Positive and Negative Syndrome Scale. The availability of the atypical antipsychotic clozapine in 1989 led to the observation that it is possible to have a treatment effect on hostility that is independent of the treatment effect on hallucinations or delusions, and independent of general sedative effects. The data supporting this notion of a specific anti-hostility effect are the most robust for clozapine as the data include specifically designed randomized, controlled clinical trials. A specific anti-hostility effect is also observable to various degrees with most of the other atypical antipsychotics, as evidenced in post hoc analyses of clinical trials originally conducted for regulatory purposes, supplemented by post hoc analyses of large effectiveness trials. The generalizability of these studies, however, may be limited. Participants in these trials were not selected for aggressive and hostile behavior. Some of the studies also excluded patients with substance use disorders. The latter is particularly important because alcohol and substance use are well known to increase risk for hostility and aggression. Nevertheless, the repeated demonstrations of the specificity of an anti-hostility effect (in terms of statistical independence of effects on other positive symptoms and of sedation) are of potential clinical importance.