Treatment of Aggressive Behavior in Brain Damage

Aggressive behavior often occurs in the setting of neuropsychiatric disorders. There are several types and patterns of aggressive behavior toward self and others. Just as one would not treat seizure disorders without first determining the semiology and type of seizure, one should not assume that all aggressive behavior can be treated with a single approach. Careful diagnosis of the aggressive behavior helps focus the treatment. Treatment may involve both medical and behavioral interventions. In this column I describe an approach that has often met with success in the context of my work with a broad variety of neuropsychiatric problems at the University of Massachusetts Neuropsychiatry Referral Center.

Type of Aggression

Begin by obtaining a thorough description of the aggressive behavior from eyewitnesses such as family members, nursing staff, or police. I use the “4P approach,” which involves determining prodrome, precipitant, purpose, and pattern. Sometimes in the context of discussion with eyewitnesses a discernible prodrome can emerge. Box 1 lists some examples of prodromal symptoms, common precipitants, causes of new-onset aggression, and common causes of irritable behavior. The presence of a precipitant can be helpful in determining environmental changes that may be helpful in limiting further aggressive behavior. Does the aggressive behavior appear to fulfill a purpose? Behavior that appears to be used as a means to an end may have diagnostic significance. Box 2 lists some questions that can be used to determine whether the behavior may have been intentional. Finally, clinicians should ask themselves whether the aggressive behavior fits a known neuropsychiatric pattern. Box 3 lists several known behavioral patterns that may include aggressive behavior. These patterns are sufficiently well described that psychiatrists should be familiar with them.

New-onset aggression of a previously well-compensating nonverbal individual may be a sign of a medical problem needing attention. This pattern indicates a need for a careful physical examination and discussion with family or care staff to determine the need for further evaluation for problems such as those listed in Box 1. Irritability is a vague symptom that can occur in a panoply of disorders. However, the differential diagnosis of baseline irritability that may facilitate aggressive behavior (Box 1) should be considered when gathering the history. Some of the focal neurobehavioral syndromes are classified as major or mild neurocognitive disorders within DSM-5, allowing for behavioral specifiers to describe the predominant behavior.

Disorders Associated With Aggressive Behavior

Aggressive behavior occurs in several psychiatric and neurodegenerative disorders described in DSM-5. It has been recommended that treatment planning for aggressive behavior that co-occurs with psychiatric disorders begin with classification of the behavior as primarily psychotic, impulsive, or organized (predatory) aggression (1). Several disorders that are less clearly delineated in DSM-5 also give rise to aggression. The most common neurocognitive syndromes that include aggressive behavior are the orbitofrontal and dorsolateral prefrontal behavior syndromes. These two syndromes, which can be compared in Table 1, often occur as sequelae of traumatic brain injury in association with dysexecutive syndrome. Right-hemisphere syndromes may be congenital or acquired. Congenital right-hemisphere syndromes are included among the causes of nonverbal learning disabilities. The aggressive behavior in these conditions may stem from social pragmatic communication deficits, failure to comprehend nuance, or paralinguistic aspects of social communication. Diencephalic behavior syndrome can occur in the setting of third ventricle tumors or hypothalamic damage. There may be polydipsia, hyperphagia, sleep phase change, or hypersexuality. The patient may demonstrate tactile or territorial defensiveness or may become agitated when access to food or drink is blocked. Brief aggressive outbursts may occur in the context of pseudobulbar palsy, stemming from bilateral white matter damage to corticobulbar pathways. Pseudobulbar palsy includes pathological affect regulation as well as dysarthria, dysphagia, facial weakness, drooling, hyperreflexia, increased jaw jerk, and extensor plantar responses. Although directed aggression does not occur during seizures, aggressive behavior may occur during the prodrome or postictal state related to epileptic seizures and can occur as an interictal phenomenon in temporolimbic epilepsy. The pattern of aggressive behavior thus differs if the brain damage involves neocortical, limbic, or diencephalic pathology (2).

A few inherited disorders have been postulated to predispose individuals to aggressive behavior toward others. Early impulsive violence and increased suicide risk have been associated with hypoglycemia and low cerebrospinal fluid (CSF) serotonin metabolites of males with early alcohol use and a family history of alcoholism (3). A Dutch kindred with monoamine oxidase A deficiency and elevated serotonin levels has been described in which male offspring with mild intellectual disability are shy and withdrawn, develop aberrant sexual behavior, and exhibit stereotyped hand movements, poor sleep, frequent night terrors, and one- to three-day clusters of behavioral outbursts. The aggressive behavior reportedly increases if the child suffers from chronic abuse (4).

Self-injurious behaviors occur in borderline personality disorder, in mood disorders, and in developmental disabilities. Congenital disorders, such as Smith-Magenis, MECP2, and Lesch-Nyhan syndromes, are often associated with self-injurious behaviors, which may be part of the self-stimulatory behaviors seen in autism spectrum disorder and other neurodevelopmental disabilities.

Neurological and cognitive examination will establish the presence of focal neurological symptoms, gray versus white matter deficits, dysexecutive syndrome, and frontal or right-hemisphere cognitive deficits and should be used to determine whether additional evaluation is needed.

Treatment

Ideally, aggressive behavior in brain-damaged individuals should be addressed by a multidisciplinary treatment team, admittedly easier to find in residential or community programs with behavioral staff. Treatment must begin with a clear description of the particular target behavior being addressed by the treatment plan and a method of counting or charting it as the primary outcome. Antecedent behaviors should be specified by the team to facilitate prediction and prevention of outbursts. Maintaining staff consistency across shifts and keeping the patient’s unstructured time to a minimum are important. Staff should seek to avoid inadvertent reinforcement of aggressive behavior by planning in advance the type of attention to be given when aggression occurs. The treatment plan should include an attempt to reduce antecedent behaviors, the introduction of rewards for alternative desirable behaviors, and implementation of one medication or behavioral plan change at a time in order to allow conclusions as to treatment efficacy. A behaviorally informed psychologist can be deployed to teach the staff or family members the principles of reinforcing desirable behaviors and to help design a tracking system. Simple rating scales such as the Overt Aggression Scale (5) allow staff to easily rate aggressive incidents. Collection of baseline data before prescribing medication allows for later comparison. The physician should have a working diagnosis that includes the type of aggressive behavior and the most likely cause before prescribing. In diagnosed psychiatric disorders, aggression is approached by first providing maximal treatment for the disorder, before adding supplementary treatment for aggression. When empirically treating aggressive episodes outside of the context of a definite psychiatric disorder, one should use an ABA treatment protocol (on-off-on) to provide more reliable evidence of response. Such an approach would not be appropriate when treating a known psychiatric disorder.

To minimize adverse effects, especially in vulnerable populations such as elderly patients with dementia, an attempt should be made to manage aggressive behavior with environmental and behavioral interventions before prescribing medication. If a medication trial is planned, the diagnostic features outlined above should inform medication choice. In the case of psychiatric causes of aggression, if the symptoms do not support the diagnosis of a psychiatric disorder, antecedent behaviors that include symptoms typically seen in a psychiatric disorder may help guide treatment. Care should be taken to verify the definition of aggressive behavior used when reading published literature on its treatment. Although a review of the evidence supporting psychopharmacologic interventions is beyond the scope of this column and the evidence supporting any pharmacologic treatment for aggressive behavior remains weak (6), the following general approaches may be useful. Anticonvulsant mood stabilizers are used in the treatment of aggression related to bipolar disorder, intermittent explosive disorder, epilepsy, and epileptiform EEG in the absence of seizures. Behavior that remains at a well-regulated normal baseline between discrete episodes may also be an indication for antiepileptic treatments, but the evidence for antiepileptic agents for treatment of aggressive behavior outside of these contexts is not strong. Lithium has been shown to be useful and is often overlooked (7). Beta blockers (or alpha-adrenergic agonists) may be used when there is traumatic brain injury, developmental disability, diencephalic aggression, and severe anxiety or when aggression occurs in response to routine requests (8, 9). Selective serotonin reuptake inhibitors may be tried for affective aggression, impulsive aggression, aggression in the context of dysphoria with or without major depression, obsessive compulsive disorder or compulsive behaviors, posttraumatic stress disorder, or for aggressive behavior that has a clear date of onset. In addition to being used for psychosis and bipolar disorder with aggression, second-generation neuroleptics may be used for severe impulsivity or other severely aggressive episodes unresponsive to other treatments. Among neuroleptics, clozapine may have the strongest evidence for use with adults. Risperidone and aripiprazole are the only medications currently approved for treatment of irritability in autism spectrum disorders (10). For aggressive behavior in appropriate diagnostic settings, anxiolytics, stimulants, or N-methyl-d-aspartate blockers are also occasionally used, albeit with caution. Regardless of psychopharmacologic intervention, good practice is to maximize treatment with a single agent before engaging in polypharmacy. In adding a second agent, consideration should be given both to pharmacokinetic interactions and treatment compliance.

Summary

Before initiating treatment of aggressive behavior, the physician should formulate a diagnosis and a hypothesis as to the underlying cause of the behavior. Carefully describing the case, conducting a detailed examination, adopting a team approach to patient care, collecting behavioral data, and following established behavioral principles all facilitate treatment. Medications should be used according to a diagnostic hypothesis rather than for undifferentiated aggressive behavior. Treatment with a single agent should be maximized before adding a second agent.