Clozapine in the Treatment of Aggression in Conduct Disorder in Children and Adolescents: A Randomized, Double-blind, Controlled Trial

Abstract

ObjectiveThis study was conducted to compare the efficacy of clozapine vs. risperidone in the treatment of aggression in conduct disorder in children and adolescents.MethodsTwenty-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 score was used as the primary outcome of the study. Secondary outcomes were Child Behavior Checklist (CBCL) externalization (CBCL-E) and internalization factors; Aggression, Hyperactivity and Delinquency subscales of CBCL-E, Child Global Assessment Scale (CGAS), Barnes Akathisia Rating Scale, and Simpson-Angus Scale.ResultsBoth 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, 0.010, and 0.021). Two subjects from the clozapine group were excluded due to a low neutrophil count at week four.ConclusionClozapine 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.

High-throughput multi-residue quantification of contaminants of emerging concern in wastewaters enabled using direct injection liquid chromatography-tandem mass spectrometry

“…In Mexico, the prevalence of psychiatric disorders has been reported as 6–16 % for males and 2–9 % for females. In children and adolescents, the prevalence is 2–10 % ( Medina-Mora et al, 2003 ; Juárez-Treviño et al, 2019 ). Clozapine is also an antipsychotic drug and was introduced in Mexico in 1994.…”

A mechanism-based group-psychotherapy approach to aggressive behaviour in borderline personality disorder: findings from a cluster-randomised controlled trial

“…This effect on overt aggression (as measured by the M-OAS) is equivalent to or even higher than those reported by RCTs of psychopharmacological agents, such as the aggression-reducing effect of divalproex in cluster B personality disorders (a 46.8% reduction) 43 or of clozapine in adolescents with conduct disorder (a 58.4% reduction). 44 To our knowledge, there have been only two psychotherapy RCTs with overt aggression as the therapy target. One, which offered a high-dose group therapy, namely democratic therapeutic community treatment, for up to 18 months to individuals with personality disorders (mostly BPD), reported a significantly higher decrease in M-OAS score 24 months after randomisation compared with TAU, with a 60% decrease from pre-therapy; however, it failed to show significant improvement after 12 months.…”

Plasma Risperidone-related Measures in Children and Adolescents with Oppositional Defiant/Conduct Disorders

“…We here did not attempt to correlate our TDM data with clinical response or daily dose, but doses do not correlate with plasma drug or metabolite concentrations with this drug [34]. However, risperidone is effectively used in pediatric age populations [35,36], as are other antipsychotics in the conditions considered here [37].…”