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January 27, 2021
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Clozapine 'optimal treatment' for violent schizophrenia patients with conduct disorder

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Clozapine appeared to be the optimal treatment for violent schizophrenia patients with conduct disorder, according to study results published in American Journal of Psychiatry.

“Although the main effect of first-generation antipsychotics is their antipsychotic action, there is strong evidence that second-generation antipsychotics, and particularly clozapine, have a broader spectrum of effects, which include control of aggression and impulsive behavior,” Menahem Krakowski, MD, PhD, of the department of psychiatry at the Nathan Kline Institute for Psychiatric Research, and colleagues wrote. “Clozapine has been reported to decrease various forms of aggression in animals, including aggression knockout mouse models that are insensitive to its sedative effect. In these various animal models, the antiaggressive effect is independent of any antipsychotic or sedative effect.”

Among patients with conduct disorder, treatment of violence in schizophrenia is a challenging problem, Krakowski and colleagues noted. In prior clinical studies, patients were not selected based on violence, and these studies did not focus on conduct disorder.

In the current study, the investigators conducted a head-to-head comparison of clozapine, olanzapine and haloperidol for treating violent schizophrenia patients with and without conduct disorder. In a 12-week double-blind trial, they randomly assigned 99 schizophrenia patients who were physically assaultive to receive one of the three drugs, and characterized participants according to presence or absence of conduct disorder before age 15 years. The investigators recorded assaults and used the Modified Overt Aggression Scale to score their frequency and severity. Further, they evaluate psychiatric symptoms using the Positive and Negative Syndrome Scale.

Results showed more frequent and severe assaults among those with a history of conduct disorder vs. those without conduct disorder. Clozapine was superior in reducing assaults vs. haloperidol and olanzapine, and olanzapine was superior to haloperidol. Patients with conduct disorder exhibited a substantially more pronounced antiaggressive efficacy for clozapine vs. haloperidol than those without conduct disorder. Clozapine was four times more likely vs. haloperidol to be linked to lower violence among patients with conduct disorder and was three times more likely to do so among patients without conduct disorder. Patients with conduct disorder exhibited a more pronounced superiority for olanzapine vs. haloperidol.

“This is the first study to examine the efficacy of clozapine in the treatment of violence in patients with schizophrenia and conduct disorder,” Krakowski and colleagues wrote. “The findings point to the superiority of clozapine, and to a lesser extent olanzapine, for these patients and have important implications for treatment. It is imperative to obtain a good history of conduct disorder, for if it is present, clinicians should consider clozapine as the primary drug for treatment.”