Independent effect
At week 6, the LSM mean change from baseline (CFB) in the PANSS hostility score was superior in both treatment groups at 6 weeks, compared with placebo (7.6 mg/24 hr: CFB, –0.4; 95% confidence interval, –0.6 to –0.2; P < .001; 3.8 mg/24 hr: CFB, –0.3; 95% CI, –0.6 to –0.1; P < .01).
The findings remained significant, even after the researchers adjusted for covariates.
For all patients, regardless of baseline PANSS hostility item score, PANSS-EC week 6 LSM CFB was greater in both treatment groups compared with placebo (7.6 mg/24 hr: CFB, –1.1; 95% CI, –1.9 to –0.4; P < .01; 3.8 mg/24 hr: CFB, –1.3; 95% CI, –2.0 to –0.6; P < .001).
Patients with a PANSS hostility score > 1 at baseline in both treatment groups also showed significant improvement in PANSS-EC score, compared with the placebo, beginning at week 2 and continuing through week 6.
“These effects of HP-3070 treatment on the PANSS hostility item score remained, even after adjustment for confounding variables, suggesting that the effect of HP-3070 on reducing symptoms of hostility may at be at least partially independent of general antipsychotic effects on hallucinations or delusions or the presence or absence of relevant medication-induced adverse effects, such as sedation or akathisia,” the authors comment.
They note that a limitation of the study is that it was conducted post hoc. In addition, the mean baseline PANSS hostility score was “low,” even among those with a score > 1, “translating to a severity level of minimal to mild,” which “limits the generalizability” of the analysis.
Important treatment target
Commenting on the study, Rifaat El-Mallakh, MD, MS, director of the Mood Disorders Research Program, department of psychiatry and behavioral sciences, University of Louisville (Ky.) School of Medicine, said, “aggression and hostility may exhibit themselves as symptoms of a psychotic illness or independent of psychosis and are an important treatment target.”
Dr. El-Mallakh, who was not involved with the study, said the “most effective anti-aggression medicine is clozapine.” He believes that it is this effect that “gives clozapine its stellar reputation,” rather than its antipsychotic effect.
“Of importance, the anti-aggression effect of clozapine is independent of its antipsychotic effect, which is an important point because if the behavior is rooted in psychosis, then successful treatment of psychosis with any agent should reduce aggression.”
The researchers “demonstrated that the effect was independent of psychosis” but because the study only recruited people with schizophrenia, the researchers “could not examine to see if the effect is independent of diagnosis,” Dr. El-Mallakh said.
“It is important to consider aggression/hostility as an independent behavior in pharmacologic studies, because it probably has its own biochemistry and neuroanatomy,” he added.
This study was funded by Hisamitsu Pharmaceutical. Dr. Citrome has received nonfinancial support from Hisamitsu Pharmaceutical and personal fees from Noven Pharmaceuticals during the conduct of the study; personal fees from numerous companies and organizations; and one-off ad hoc consulting for medical education companies such as Medscape, NACCME, NEI, Vindico, and universities and professional organizations/societies outside the submitted work. He has stocks and received royalties from numerous companies and organizations. Dr. El-Mallakh is a speaker for Noven, as well as Indivior, Intracellular, Janssen, Lundbeck, Otsuka, Sunovion, and Teva.
A version of this article first appeared on Medscape.com.