Although medication is commonly prescribed to address serious and persistent maladaptive aggression in youth (Pappadopulos et al., 2002
; Patel et al., 2002
), critical methodological challenges make research on aggression difficult to execute and interpret. Our limited understanding of the causes of aggression prevents its inclusion in the current US diagnostic framework. Co-morbid aggression is therefore often regarded as a nuisance, rather than a target of intervention in medication trials.
Current research considers aggression a physical behavior that generally causes harm or damage to objects or living beings (Volavka & Citrome, 1999
). However, a developing literature distinguishes between “impulsive” aggression (“affective, hot”) and “predatory” aggression (“planned, profitable and self-controlled, cold”), arguing that impulsive aggression may be most amenable to pharmacotherapy (Connor et al., 2004
; Steiner et al., 2003
; Vitiello et al, 1990
; Vitiello & Stoff, 1997
; Jensen et al., in revision
). While these subtypes are still nascent in their exact meanings and classification, they may respond to different treatments and lead to different long-term outcomes (Gillberg & Hellgren, 1996). The studies reviewed in this paper fail to discriminate between types of aggression and, therefore, do not address the clinical impact of treatment on different forms of aggression. Nevertheless, we acknowledge that future research must address how this distinction impacts treatment. To this end, the field would benefit from a generally accepted clinical measure of aggression with adequate sensitivity and reliability that could be used in RCTs to help further refine treatment decisions.
The present review suggests that the largest effects for the treatment of pediatric aggression will most likely be seen with MPH for ADHD with co-morbid disruptive behavior problems (mean ES = .90) and risperidone for youth with CD and subaverage IQ (mean ES = .90). Overall, mood stabilizers, SNRIs, antidepressants, and α-2 agonists produced relatively low to medium ES values (range = 0.3 to 0.5) and may be less useful in the management of co-morbid conditions in children.
The large ESs of MPH and risperidone found in this review are relatively powerful clinical effects, and can be better understood in the context of agents used for other disorders. The ESs of MPH and risperidone for aggression are equivalent to those seen in stimulants for ADHD, which are perhaps the strongest treatment improvements observed in child psychiatry. Another revealing contrast is that a meta-analysis of SSRI use for obsessive compulsive disorder (Geller et al., 2003
) showed only a moderate ES of 0.46 (combined n = 1044, mean age ages 6–19 years, 2 studies). Further, in a study of adolescents with depression, treatment with fluoxetine and cognitive behavioral therapy (CBT) produced an ES of 0.98, while fluoxetine alone was 0.68 and CBT alone was 0.03 (March et al., 2004
). Thus, compared with agents used for other conditions, certain medications may have large clinical effects on impulsive aggression. Given the heterogeneity inherent in early onset maladaptive aggression, however, pharmacotherapy should never be the sole treatment provided to the patient.
The conclusions that can be drawn from this review on the pharmacotherapy of aggression are limited by the quality and breadth of the existing literature. The pool of available data was constrained by a clear publication bias for positive studies which prevented us from exploring all study findings on aggressive behavior. Furthermore, RCTs on newer atypical agents and combined medication regimens were notably lacking in the existing literature. Important treatment issues regarding diagnosis may have also been obscured, as we grouped studies by medication class in order to review the existing RCT data on aggression.
From a clinical perspective, RCTs meeting review criteria do not reflect conditions encountered in “real-world” treatment settings. While psychotropic agents are often administered over the course of several months and years, the average duration of RCTs reviewed in this paper was less than 6 weeks. Also, treatments for aggressive adolescents remain largely understudied, as most trials focused young clinical samples (average age = 10.5 years). The limited population sample was particularly apparent in studies of lithium, which only included inpatients with severe symptoms. Furthermore, it was difficult to assess the effect of medication treatments on aggression because of the lack of valid measurement scales.