Once you have tried the various non-pharmacological approaches to aggression (see this month’s interviews with Dr. Connor and Dr. Greene for suggestions), you will have to turn to what is generally the second choice—using medications. In this article, I’ll discuss a practical approach to choosing and prescribing medications for childhood aggression. See the accompanying table for details about dosing and side effects.
Before discussing specific agents, it is important to note that conduct disorder and oppositional defiant disorder respond infrequently to medication alone—generally it can only augment environmental and behavioral interventions. Also, I find that often the most difficult to treat patients have unrecognized long-standing anxiety or learning disabilities. So when you are having trouble achieving a response, you may want to start the diagnostic process over again with this in mind. In patients with autism, developmental disabilities or traumatic brain injury, slow all medication changes down substantially. This population may become aggressive merely in response to rapid dose changes irrespective of the underlying disorder. The dictum for using medications in children, “start low,
Adrenergic Agents. I generally start with alpha adrenergic agents when I’m unsure about the cause of aggression, because these drugs work quickly and are fairly safe. These medications, originally developed for the treatment of hypertension, work by interrupting the fight or flight sensation in the body, and are similar in this regard to the beta blocker propranolol—used off-label for aggression in adults. The theory is that if you can prevent the somatic feeling of agitation, you can reduce the cognitive component of aggression as well. Alpha adrenergic agents seem to work by giving the child an extra couple of seconds to think about a situation before reacting.
I will usually start with guanfacine (Tenex) because its longer half-life (15 hours) allows for once a day dosing, usually at night. However, Dr. Jess Shatkin of the NYU Child Study Center tells us that in his experience Tenex works better when dosed twice a day: “I generally start with a late afternoon dose and then add a morning dose once the evening dose has proven tolerable.” Guanfacine XR (Intuniv) was recently introduced by Shire and is the only alpha adrenergic agent approved for ADHD. We await more experience with it, but the extended release mechanism may make it a good once-a-day option for treating aggression.
With regard to clonidine (Catapres), because children metabolize it very quickly, this medication requires dosing throughout the day, which can be hard for families. It comes in a patch form, however, which eliminates the need for multiple daily doses.
Antidepressants. I find antidepressants helpful for treating aggression in several ways. Tricyclics, such as desipramine, can be used to target the impulsivity and conduct disorder aspects of ADHD. SSRIs, on the other hand, do not work for ADHD symptoms, but they are remarkably effective treatments for anxiety disorders in children. A significant cause of aggression in children is anxiety—a fact that is often missed, in part because aggressive kids will often not admit to being anxious.
How does anxiety lead to aggression? The emotional logic varies from child to child. For example, a child with obsessive compulsive disorder might have the intrusive thought that if he puts his shoes on his family will die. If someone says, “Go put your shoes on,” he will resist it with the same intensity that you or I would fight against something that would hurt our families, including becoming aggressive. Another example is the child with generalized anxiety disorder, who may be immobilized by worries. He may avoid homework because of worries like, “Can I get it done? Can I do it right? Will I lose it? Will I get yelled at by my teacher?” If he is told to do his homework by his parents, it may feel like he is being asked to jump into a shark tank, and he may fight against it, becoming aggressive. I find that SSRIs can often prevent aggression in such children by treating the underlying anxiety that drives it.
Stimulant and Non-Stimulant Treatments for ADHD. Again, these work by treating the underlying disorder. In the case of ADHD, impulsivity seems to drive the aggression, as well as the oppositional/defiant characteristics of some children with this diagnosis. Both symptoms seem to remit with effective treatment of ADHD. Many kids have comorbid anxiety, however, that may worsen with stimulants. Remember that atomoxetine (Strattera) is serotonergic, so be careful of drug interactions if you combine Strattera with SSRIs for treating anxiety and ADHD. Check for learning disabilities as well—not only are they commonly comorbid, they are also a common source of agitation and defiance around homework.
Antipsychotics. Most child psychiatrists will not use antipsychotics for aggression until less risky measures have failed. For instance, when you have tried psychotherapy, family interventions, more benign medications such as alpha adrenergics and SSRIs, and yet the aggression persists, antipsychotics are an option. I may use antipsychotics earlier in children who are physically dangerous and at imminent risk of serious harm, or in children who are about to be kicked out of the home or other living situation because of their behavior. In such situations, I take advantage of the best features of antipsychotics—they work very quickly, and very well.
My antipsychotic of first choice is usually aripiprazole (Abilify), because it generally has fewer side effects, especially in terms of weight gain and lipids. In addition, the fact that it is a partial D2 agonist, rather than a full D2 antagonist, may theoretically give it some long term side effect advantages. For example, while the data is sparse, Abilify may be less likely to cause tardive dyskinesia than other atypical antipschotics.
After Abilify, I will turn to Risperdal, partly because it, like Abilify, has FDA approval for the treatment of irritability in autism, and partly because my experience is that it seems to work particularly well for aggression. Zyprexa is my third choice, because it appears to have better mood stabilizing effects than other antipsychotics. However, it can cause tremendous weight gain and sometimes hypotension, so it requires careful monitoring.
Mood Stabilizers. My mood stabilizer of first choice is Lamictal (lamotrigine) because it has few side effects and works fairly well for the common clinical profile of the child with irritable depression who may or may not have bipolar disorder. In fact, I tend to use Lamictal before an atypical antipsychotic in such children. Lithium, Depakote, and Trileptal are my aggression treatments of last resort because of a combination of severe side effects and the need for blood monitoring. Lithium can cause cognitive dulling, hypothyroidism, and renal problems. Depakote commonly causes weight gain, sedation, and nausea, and possibly polycytic ovarian syndrome. Trileptal is well tolerated but requires blood monitoring because of the small risk of hyponatremia and lowered white blood count. On the other hand, lithium and Depakote can be remarkably effective for aggression, and Depakote has a long track record of pediatric use in the treatment of epilepsy.
Benzodiazepines. While benzodiazepines can be helpful for pediatric anxiety, they are usually avoided in aggressive children because they can be disinhibiting. For this reason, benzodiazepines are not included in the medication chart.