Aggression and Autism Impulsivity

Impulsive behavior and aggression are present in a broad range of disorders. Although there have been some attempts to develop specific anti-aggression drugs or the "serenic" class of medications, the current psychopharmacological treatment strategy involves treating aggression as part of each particular syndrome. Impulsive or aggressive acting out behavior, for example, is one of the central behavioral features of the borderline personality disorder and is dealt with as a part of the whole disorder, which must be fully treated. These and other issues related to aggression are addressing in a symposium, sponsored by Abbott Laboratories, at the 153rd annual meeting of the American Psychiatric Association.

Impulsivity is the tendency to participate in spur of the moment behaviors that often have a high probability of a negative outcome. Impulsivity is associated with higher rates of aggression, suicide, substance abuse, as well as accidents. Impulsivity is a component of numerous psychiatric disorders including Cluster B personality disorders, developmental disorders, impulse control disorders, substance abuse, attention deficit hyperactivity disorder (ADHD), Tourette's syndrome, posttraumatic stress disorder (PTSD), and bipolar disorder, among others.

Many classes of medications have been used to treat impulsivity. These include the selective serotonin reuptake inhibitors (SSRIs), 5-HT receptor agonists and antagonists, lithium, anticonvulsants, typical as well as atypical neuroleptics, beta blockers, alpha antagonists such as clonidine, opiate antagonists such as naltrexone, and dopamine agonists such as buproprion and amphetamines.

Borderline personality disorder is a chronic often debilitating disorder characterized by rapid mood shifts, intense and often unstable relationships, self-damaging impulsive behavior, and feelings of intense anger. Two percent of the population has a lifetime history of borderline personality disorder. Although tricyclic and monoamine oxidase (MAO) inhibitors have been somewhat helpful in controlling the symptoms of borderline personality disorder, their safety profile makes them difficult to use on a regular basis. Tricyclic antidepressants may increase irritability because they stimulate the norepinephrine system. SSRIs have been shown to be helpful in controlling some of the affective symptoms of borderline personality disorder, but it is not clearly a generalizable finding. Benzodiazepines may have a disinhibitory effect similar to alcohol and they can therefore increase impulsivity. The potential for addiction in a population already predisposed towards toward substance abuse is high. Benzodiazepines therefore should not be used on a regular basis.

Several mood stabilizers have been tried. Lithium may decrease anger and aggression but may be lethal in an overdose. In some cases aggression is reported to have increased. In an open label trial of divalproex in 11 outpatients with borderline personality disorder, Eric Hollander, MD, of Mt. Sinai Medical Center in New York, New York, and colleagues^[1] found that there was a significant decrease in global functioning and irritability in the 8 completers.^[2] This was followed by a double-blind study of divalproex in 21 patients and were randomized to divalproex or placebo.^[3] In completers there was a significant improvement, with the Clinical Global Impression decreasing from 4 to 2.2 (P<0.01) and the Global Assessment Scale increasing from 52 to 66.7 (P<.003). None of the placebo-treated patients responded, while 42% of the drug-treated patients demonstrated improvement. Although the results must be considered preliminary, there is some evidence that divalproex may be helpful with borderline personality disorder.

Autism is a developmental disorder that has 3 key dimensions, including speech and language deficits, social deficits, and the tendency to have a very narrowed range of interests. It has been hypothesized that there may be increased sensitivity of the 5-HT_1B and this may relate to the repetitive behaviors. Fluoxetine has been shown to be helpful at times. Epilepsy occurs in 20% of autistic children and electroencephalograph (EEG) abnormalities occur in 50%.

Many psychopharmacological agents have been used to treat impulsivity. The current talk focused on the use of divalproex in borderline personality disorder and autism, 2 disorders with high levels of impulsivity. This medication appears to be helpful in treating a broad range of symptoms in these disorders, regardless of whether EEG changes are present.

Agitation and Aggression in the Elderly

Pierre N. Tariot, MD,^[4] of Monroe Community Hospital in Rochester, New York, discussed the causes of aggression in the elderly. The primary cause of aggression is dementia, although one should search for other underlying medical, neurological, psychiatric, and/or environmental causes that may account for or exacerbate the behavior. There are 2 forms of agitation in the demented patient. One is the verbal or physical nonaggressive behavior that occurs in 50% of demented individuals. One third to one half of patients will demonstrate overt aggressive behavior. This may take the form of verbal, physical, or sexual aggression. It is imperative that the clinician attempt to identify any underlying cause that might precipitate aggressive behavior. For example, the patient may have developed a urinary tract infection that needs to be treated in place of psychotropic medication.

Several nonpharmacological interventions could be used to address the issues of agitation and aggression. Consistent daily routines should be implemented and social and physical stimulation should be optimized. Education and support should be given repeatedly to the caregivers to ensure consistent treatment plans and identification of problems.

Pharmacotherapy should be tailored towards the specific target symptoms (ie, depression, psychosis, or mania). Use of atypical rather than typical antipsychotic agents is recommended. Depressive symptoms should not be missed because they by themselves may result in increased confusion, paranoia, or other symptoms. Conventional neuroleptics have been shown to be approximately 18% more effective in controlling agitation than placebo. Low doses usually are effective. A flexible dose strategy was used and risperidone (1-2 mg) appeared to be more effective than 0.5 mg in decreasing aggression. Adverse effects increased at the 2-mg dose.^[5] A more recent unpublished study of olanzapine may indicate effectiveness at 5 mg.

Mood stabilizing agents such as divalproex are being used more in the treatment of aggressive behavior to find alternatives to antipsychotic treatment. The anticonvulsants may result in greater symptomatic improvement of impulsivity and aggression.

Summary

Mood stabilizers are found to be helpful in the elderly as well in other clinical populations. Further comparisons between these agents and other classes of medications will help us to determine which medications are suited for which specific clinical situations.

References

1. Hollander E, Novotny SL, Allen A, Cartwright C, Bienstock C. Impulsivity in aggression: borderline personality disorder and autism. Program and abstracts from the 153^rd Annual American Psychiatric Association Meeting; May 13-18, 2000; Chicago, Illinois. Abstract 32A.
2. DJ, Simeon D, Frenkel M, Islam MN, Hollander E. An open trial of valproate in borderline personality disorder. J Clin Psychiatry. 1995 Nov;56(11):506-10.
3. Hollander E. Program and abstracts from the Update on Personality Disorders meeting; March 6-8, 1998; Atlanta, Georgia.
4. Tariot PN. Agitation and aggression in the elderly. Program and abstracts from the 153^rd Annual American Psychiatric Association Meeting; May 13-18, 2000; Chicago, Illinois. Abstract 32B.
5. de Deyn PP, Katz IR. Control of aggression and agitation in patients with dementia: efficacy and safety of risperidone. Int J Geriatr Psychiatry. 2000;15(suppl 1):S14-S23.