Consensus on Treatments for Aggression in Youth

Acute aggression in child and adolescent psychiatric patients should be addressed with psychosocial crisis management before resorting to medication, according to an expert consensus panel convened by the Center for the Advancement of Children's Mental Health at Columbia University and the New York State Office of Mental Health. Their two-part report in the February Journal of the American Academy of Child and Adolescent Psychiatry reviewed the safety and efficacy of treatments for aggression in young patients (Schur et al., 2003) and offered treatment recommendations and rationale (Pappadopulos et al., 2003).

The Treatment Recommendations for the Use of Antipsychotics for Aggressive Youth (TRAAY) were formulated from expert consensus and assessment of available evidence. The recommendations address severe impulsive aggression, including verbal threats of violence toward oneself or others. The recommendations do not extend to predatory aggression or what has been described as planned and self-controlled aggressive behavior (Vitiello et al., 1990).

Although TRAAY were developed independently of the American Academy of Child and Adolescent Psychiatry (AACAP), they complement the Academy's practice parameters for preventing and managing aggressive behavior (Masters et al., 2002). Unlike other treatment guideline projects, such as those of the AACAP, the American Psychiatric Association and the Texas Medication Algorithm Project (TMAP) (Miller et al., 1999), which consider specific diagnostic entities, TRAAY address the behavioral manifestations of patients with a variety of disorders.

Also unlike these other projects, TRAAY were developed with relatively little controlled data to draw upon. The panel explained, "Our target population is composed of patients who are excluded from most research." With the absence of controlled research, interventions with aggressive youth appear to have evolved from heuristic clinical practices, adult treatment literature and case reports.

In order to provide more substantive treatment rationales and coherent strategies, the TRAAY panel reviewed intervention methods and any evidence for efficacy, utilizing both literature and patient chart review (Schur et al., 2003). To develop wellfounded recommendations despite scarce controlled data, the panel also elicited expert opinion through focus groups and surveys and finalized recommendations in a Medication Consensus Workshop (Pappadopulos et al., 2003).

The panel explained, "We have tailored our actions to utilize the evidence base along with a rigorous expert consensus process to address areas for which research is lacking."

Intervention Safety and Efficacy

In their review of clinical trials, the panel found that many youth hospitalized for severe aggression improved shortly after admission without active medication treatment (Malone and Simpson, 1998). They credited "nonspecific therapeutic intervention" for effectively reducing aggression, particularly aggressive symptoms with affective and/or explosive characteristics (Schur et al., 2003).

"In some cases, psychosocial interventions alone may be effective treatments," the panel wrote. "When psychotropic medications are prescribed, they may be most effective when administered as part of a comprehensive psychotherapeutic and educational program or within a 'therapeutic milieu'" (Schur et al., 2003).

Psychosocial interventions supported by clinical data include contingency management programs, such as token economies; systematic social skills training, including problem solving; and anger management. Individualized program components, such as behavioral "report cards," were found useful for reducing specific behaviors like bullying or provocations (Schur et al., 2003).

Although there is evidence of effective nonpharmacological interventions for aggression in youth, the panel cautioned, "Because most studies have not focused specifically on aggression per se, there is a need for more controlled research focusing specifically on behavioral and psychosocial intervention for carefully defined aggression among well-characterized samples of youth in specific settings" (Schur et al., 2003).

In considering pharmacotherapy, the panel characterized antipsychotics as the core treatment for aggression in children and adults. The panel relegated typical antipsychotics to second-line status behind atypical antipsychotics, however, due to the newer agents having lower risk for extrapyramidal symptoms, tardive dyskinesia, neuromalignant syndrome and cognitive impairment (Pappadopulos et al., 2003).

Despite increasing use of atypical antipsychotics to treat symptoms of aggression in youth, the panel found little controlled evidence of their efficacy and safety for this purpose and no data indicating the superiority of one atypical agent over another for aggressive behavior.

Recommended Treatments for Aggression

The first of the two-part report reviewed published controlled studies, articles pending publication and case reports. Risperidone (Risperdal), clozapine (Clozaril), olanzapine (Zyprexa), quetiapine (Seroquel) and ziprasidone (Geodon) were reviewed. Stimulants, mood stabilizers, selective serotonin reuptake inhibitors, a-2 adrenergic agonists and ß-adrenergic blockers were also briefly reviewed.

The panel recommended that future clinical trials examine atypical antipsychotic efficacy in treating different subtypes of aggression. They also suggested that subjects should be divided by age group (e.g., 8 through 12 versus 13 through 18) to determine if the groups respond differently to medication choices. The panel also recommended directly comparing atypical antipsychotics for safety and tolerance and comparing mood stabilizers to atypical antipsychotics. In addition, the panel recommended that additional studies be conducted with b-blockers and with combinations of medication classes.

"When one considers the frequency with which aggressive youth are treated with psychotropic medications, as well as the gaps in our knowledge of the long-term safety and efficacy of these practices, it is clear that controlled trials are urgently needed in this area" (Schur et al., 2003).

The panel developed 14 main recommendations for the treatment phases of evaluation, acute treatment, stabilization and maintenance (Due to copyright restrictions, this Figure cannot be reprinted online. Please see p7 of the print edition-Ed).

The panel recommended a comprehensive psychiatric diagnostic interview with all new patients and their parents/guardians before prescribing, changing or discontinuing medication. The panel cautioned that medication adjustments before adequate evaluation can confound diagnosis.

"Clinicians should use ... [clinical] information along with the diagnostic interview to develop a conceptual-etiological model and clinical formulation of the patient's problems, and use these hypotheses to guide all interventions, including the use of medications" (Pappadopulos et al., 2003).

The panel recommended utilizing standardized, validated rating scales of target symptoms, such as the Modified Overt Aggression Scale (MOAS), early and periodically throughout treatment to inform intervention strategy and assess outcome.

"The systematic, routine tracking of target symptoms in severely disturbed youth with complex behavior problems holds the promise of optimizing treatments" (Pappadopulos et al., 2003).

The panel considered psychosocial and educational interventions as first-line treatments and recommended their continuation with any required medication. An ideal therapeutic milieu, in the panel's judgment, includes contingency management programs, skills training programs, individualized interventions and psychoeducational programs.

The panel suggested that pharmacotherapeutic agents should be selected to treat primary disorders and aggressive symptoms. They favor monotherapy, when possible, to facilitate assessment of treatment regimen effectiveness and side effects and to enhance adherence to the regimen. The panel conceded, however, that monotherapy may not always be sufficient.

"Clinical experience indicates that the severity and frequency of aggressive symptoms often necessitate the simultaneous use of antipsychotic medications along with first-line treatments for the primary conditions" (Pappadopulos et al., 2003).

The panel preferred atypical antipsychotics to typical antipsychotics because of their safer acute side-effect profiles, in spite of weight gain and endocrinologic side effects associated with atypical agents. The panel maintained that these do not negate the advantages of the atypicals acute use.

"However, the choice of a particular atypical antipsychotic medication should be made based on patient/ guardian acceptability, comorbid general medical conditions, prior individualized drug response, side effect profile, and long-term treatment planning" (Pappadopulos et al., 2003).

The panel recommended a conservative dosing strategy of "start low, go slow, taper slow." They noted evidence of youth responding to lower antipsychotic doses than adults but possibly not before two weeks of treatment. The panel cautioned that patients should be monitored for signs of withdrawal dyskinesia during the period of gradual dose tapering before discontinuation.

For acute and emergency treatment of aggression, the panel recommended psychosocial crisis management before medication. It urged facility staff to develop a range of intervention options to prevent or reduce likelihood of escalating aggression.

"Psychosocial interventions to help patients regain self-control during this period can help avoid the need for chemical and physical restraints" (Pappadopulos et al., 2003).

The use of stat or as-needed medications should be minimized, according to the panel. If these are frequently necessary, the panel suggested imposing dose and frequency ceilings or, preferably, supplanting them with optimized dosages on a fixed schedule.

"The emergency use of medication to control behavior should not be considered a standard treatment for inpatient children and adolescents who manifest aggressive and disruptive behaviors" (Pappadopulos et al., 2003).

A medication trial should be of adequate duration and dose before changing medications. If the initial atypical antipsychotic is ineffective, the panel recommended an alternative atypical antipsychotic before another drug category is tried (Pappadopulos et al., 2003). In the TRAAY schema, failure to respond to two adequate trials of atypical antipsychotics will warrant changing to a mood stabilizer, a typical antipsychotic or a drug combination. A partial response to an atypical antipsychotic could be heightened by a mood stabilizer, the panel noted, but the combination should only be employed after reassessing diagnosis and the adequacy of behavioral interventions and of the pharmacotherapy of the primary disorder, including dose and duration.

The panel recommended routine and systematic monitoring of medication side effects, and tapering to discontinue one or more combined medications if response is not forthcoming. In reducing polypharmacy, the panel suggests deleting first those agents with the most dangerous side effects or adverse interaction potential, or side effects, which could be misinterpreted as treatable symptoms, or those having little empirical data on efficacy. An antipsychotic dose that has been effective for aggression associated with psychotic illness might also be reduced, according to the panel, after approximately six months without aggressive symptoms.

In concluding, the panel cautioned, "To avoid the risk of 'chasing symptoms' rather than treating the primary disorder, these recommendations should not be used in isolation all decisions must be guided by a biobehavioral hypothesis that is revised as new information about the patient's response to different agents is revealed" (Pappadopulos et al., 2003).

References:

References

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