Youth Aggression: Economic Impact, Causes, Prevention, and Treatment

Diagnosis-specific pharmacotherapy should be the first-line treatment to target aggressive behavior, including²³: stimulantsor atomoxetinefor attention-deficit/hyperactivity disorder (ADHD), antidepressants for depressive disorders, mood stabilizers for bipolar disorders, and antipsychotic agents for psychotic disorders. However, additional pharmacologic interventions are often needed in patients who are seriously aggressive.

Dunn and colleagues²⁴ conducted an open-label study in 24 adolescents with ADHD, oppositional defiant disorder, or conduct disorder who exhibited severe aggressive outbursts, according to the Modified Overt Aggression Scale. The initial treatment consisted of 3 weeks of 54 mg/d of extended-release methylphenidate monotherapy, followed by 9 weeks of a combination of extended-release methylphenidate and quetiapine. Quetiapine was given at dosages up to 600 mg/d. After 12 weeks, verbal aggression and physical aggression toward self, others, and property declined significantly. Both the diagnosis-specific medication and the atypical antipsychotic appeared to contribute to improvement. However, this was an open-label study without placebo or active control. It is unclear how much of a placebo effect, monotherapy with methylphenidate, or the combination treatment contributed to the results.

Connor and associates²⁵ conducted a randomized, placebo-controlled monotherapy study with quetiapine treatment for aggressive conduct disorder. Nineteen adolescents participated in this 7-week study. Dosing was flexible; the average dosage of quetiapine at study end point was 300 mg/d 6 168 mg/d. Eight of 9 patients on medication improved, compared with 1 of 10 on placebo, according to a clinical global impression (CGI) score of 2. Quetiapine appeared to be well tolerated, although data on weight and metabolic parameters were not reported.

Atypical antipsychotics have become the mainstay of pharmacotherapy for aggression, and their use in children and adolescents has increased significantly in the last decade.²⁶ Reasons for this increase may be their effectiveness; their fast onset of action, which makes them useful in acute settings; and their improved neurologic safety profile. Recently, however, significant concern has been raised about their metabolic side effects.

The American Psychiatric Association and the American Diabetes Association have ranked the atypical antipsychotics based on their likelihood to induce metabolic abnormalities. Aripiprazole and ziprasidone were characterized as being least likely to induce weight gain and metabolic side effects. Because of these potential advantages, an open nonrandomized trial of aripiprazole or ziprasidone in a community clinic population of aggressive children and adolescents was performed.²⁷ Forty-six patients (mean age of 11.9 6 2.6) were administered the Mini International Neuropsychiatric Interview and the Child/Adolescent Symptom Inventory. Conduct, bipolar, and depressive disorders were the most common diagnoses. The primary outcome measure was the Overt Aggression Scale. Patients with significant aggressive behaviors were started on aripiprazole (n = 24) or ziprasidone (n = 22). Eighteen patients were taking concomitant anti-ADHD medication.

After 2 months, 34 patients remained in treatment, with an average dosage of aripiprazole of 4.5 mg/d 6 2.3 mg/d and of ziprasidone of 42.9 mg/d 618 mg/d. The average rating on the Overt Aggression Scale improved 63% and the average CGI score was 2.1 (much improved). There were no statistically significant differences between the aripiprazole group and the ziprasidone group in the primary outcome measure at baseline and after 2 months of treatment. However, 3 times more patients on ziprasidone than those on aripiprazole dropped out because of sedation. No other side effects were prominent, although weight change and metabolic indices require further study.

Aggression in youth has an enormous societal impact--economically, clinically, and in terms of human suffering. While primary prevention is clearly desirable, the clinician is more involved with secondary and tertiary prevention and treatment efforts. Controlled studies are needed to sort out which medications or combinations of medications are most effective in controlling aggression in young patients. Treatment that impacts the many biological, psychological, and social factors related to aggression--and is delivered within the patient's environment--may be the most clinically effective and economically sound modality.

Dr Bastiaens is associate clinical professor of psychiatry at the University of Pittsburgh and is associated with Family Services of Western Pennsylvania. He reports that he is on the speakers' bureau and is a consultant for Bristol- Myers Squibb, Eli Lilly, Forest Laboratories, GlaxoSmithKline, Pfizer, and Takeda. He has received research honoraria from Forest Laboratories, McNeil Consumer Healthcare, and Janssen.

Ms Bastiaens is an undergraduate student at Davidson College, Davidson, NC. She reports no conflicts of interest regarding the subject matter of this article.