Clozapine in the treatment of aggression in conduct disorder in children and adolescents: a randomized, double-blind, controlled trial
Myrthala Juárez-Treviño *, Antonio Costilla Esquivel , Lilia Marytza Leal Isida , Dionicio Ángel Galarza Delgado , Manuel Enrique De la O Cavazos , Lourdes Garza Ocañas , Rosalinda Sepúlveda Sepúlveda
1Universidad Autónoma de Nuevo León, 2Universidad Autónoma de Nuevo León, 3Instituto Tecnológico y de Estudios Superiores de Monterrey, 4Universidad Autónoma de Nuevo León, 5Secretaría de Salud del Estado de Nuevo León, 6Universidad Autónoma de Nuevo León, 7Chan School of Public Health, Harvard University, Boston, MA, USA
Received: January 18, 2018; Revised: March 22, 2018; Accepted: March 22, 2018; Published online: March 22, 2018.
© The Korean College of Neuropsychopharmacology. All rights reserved.

Objective: To compare the efficacy of clozapine vs. risperidone in the treatment of aggression in conduct disorder in children and adolescents.
Method: Twenty-four children with conduct disorder aged 6 to 16 years were randomized in a prospective, double-blind trial into two groups to receive clozapine or risperidone for 16 weeks. The Modified Overt Aggression Scale (MOAS) score was used as the primary outcome of the study. Secondary outcomes were CBCL externalization and internalization factors (CBCL-E, CBCL-I); Aggression, Hyperactivity and Delinquency subscales of CBCL-E, Child Global Assessment Scale (CGAS), Barnes Akathisia Rating Scale (BARS) and Simpson-Angus Scale (SAS).
Results: Both antipsychotics were similarly effective in the primary outcome and in most of the secondary ones. Clozapine was more effective in CBCL-E, the delinquency subscale and the CGAS scores than risperidone (p= 0.039, p= 0.010, p= 0.021). Two subjects from the clozapine group were excluded due to a low neutrophil count at week four.
Conclusions. Clozapine and risperidone are effective for short-term treatment of aggression in children and adolescents with conduct disorder. Clozapine was more effective than risperidone in Conduct Externalization Factors, Delinquency trait and Global Functioning in children and adolescents. Stronger efficacy of clozapine should be investigated in larger sample sizes using pharmacogenomic studies. White blood cell counts need to be monitored when prescribing clozapine.

Keywords: clozapine, risperidone, conduct disorder, children, adolescent