REVIEW OF: Krakowski M et al, Am J Psychiatry 2021;178(3):266–274

STUDY TYPE: Randomized controlled trial

We often struggle to find effective interventions for aggressive behavior in patients with schizophrenia. For patients with a history of conduct disorder, the task is even more challenging. Patients with schizophrenia will often have shown symptoms of conduct disorder before age 15, although establishing the diagnosis sometimes requires digging in the history since the psychotic disorder may overshadow other symptoms. To make the conduct disorder diagnosis, look for a history of the following during childhood and adolescence: bullying or threatening behaviors, a chronic disregard for rules, criminal activity (eg, stealing, arson, sexual assault, battery), and a lack of empathy or remorse.

In a previous study, the authors demonstrated that clozapine is effective in reducing aggression and impulsive behavior in patients with schizophrenia (Krakowski M et al, Arch Gen Psychiatry 2006;63(6):622–629). But does clozapine also reduce aggression in patients who additionally have a history of conduct disorder?

The authors examined this question by enrolling 99 subjects with schizophrenia in a 12-week double-blind trial conducted in a psychiatric research unit. All subjects had a history of being physically assaultive, and about half (n = 53) had a history of conduct disorder prior to age 15. Subjects were randomly assigned to receive clozapine (n = 33), olanzapine (n = 34), or haloperidol (n = 22), and the frequency and severity of assaults were scored on the Modified Overt Aggression Scale (MOAS). The MOAS total score and the physical assault sub-score were compared across groups.

For all subjects, clozapine was superior to olanzapine and haloperidol in preventing violent behavior, and olanzapine was superior to haloperidol. However, for subjects with a history of conduct disorder, clozapine’s efficacy in preventing violence was particularly high: These subjects were over three times as likely to have a lower MOAS score and four times as likely to have a lower physical assault score compared to subjects on haloperidol. Subjects without a conduct disorder history also benefited from clozapine, but not as dramatically: They were 1.9 times as likely to have a lower MOAS score and 2.7 times as likely to have a lower physical assault score compared to subjects on haloperidol.

CHPR’S Take: For patients with schizophrenia and a history of conduct disorder, clozapine appears significantly more effective in reducing violent behavior compared to olanzapine and haloperidol. Haloperidol seems to be less effective than clozapine or olanzapine for this patient population.