Treatment Of Impulsive Aggression Research Articles

Toxicity assessment of molindone hydrochloride, a dopamine D2/D5 receptor antagonist in juvenile and adult rats

Neuroleptic drug molindone hydrochloride is a dopamine D2/D5 receptor antagonist and it is in late stage development for the treatment of impulsive aggression in children and adolescents who have attention deficient/hyperactivity disorder (ADHD). This new indication for this drug would expand the target population to include younger patients, and therefore, toxicity assessments in juvenile animals were undertaken in order to determine susceptibility differences, if any, between this age group and the adult rats. Adult rats were administered molindone by oral gavage for 13 weeks at dose levels of 0, 5, 20, or 60 mg/kg-bw/day. Juvenile rats were dosed for 8 weeks by oral gavage at dose levels of 0, 5, 25, 50, or 75 mg/kg-bw/day. Standard toxicological assessments were made using relevant study designs in consultation with FDA. Treatment-related elevation in serum cholesterol and triglycerides and decreases in glucose levels were observed in both the age groups. Organ weight changes included increases in liver, adrenal gland and seminal vesicles/prostate weights. Decreases in uterine weights were also observed in adult females exposed to the top two doses with sufficient exposure. In juveniles, sexual maturity parameters secondary to decreased body weights were observed, but, were reversed. In conclusion, the adverse effects noted in reproductive tissues of adults were attributed to hyperprolactinemia and these changes were not considered to be relevant to humans due to species differences in hormonal regulation of reproduction. On the whole, there were no remarkable differences in the toxicity profile of the drug between the two age groups.

P-944 - Neuroticism as a predictor of impulsive aggression response to fluoxetine in borderline personality disorder

Introduction Borderline personality disorder (BPD) is characterized by impulsivity with emotional and behavioral dysregulation. Inappropriate anger becomes a central problem of these patients who underwent aggressive behavior against themselves or against other. Impulsive aggression has been consistently related with serotonergic dysfunction. Drug therapy with SSRIs has proven effective in treatment of impulsive aggression in varying amounts, but still there have not been described clinical predictors of good response to this treatment. Is known that neuroticism is a stable trait in BPD, also related to serotonergic dysfunction. Aims To investigate the relationship between neuroticism and clinical response to fluoxetine in impulsive aggression in BPD. We hypothesized that the level of neuroticism at baseline may predict aggression response to pharmacologic treatment. Methods 59 patients were recruited, all meet DSM IV criteria for BPD according to IPDE. They did not fulfill criteria for axis I diagnoses or other personality disorders. Patients were treated with fluoxetine (Prozac®) for 12 weeks, in doses 20 to 60 mg. Aggression was measured with OAS-M. Temperament was evaluated with NEO-PI-R. Results Multiple regression analysis of OAS-M reduction at endpoint as dependent variable, and temperament as independent variables shown a significant predictive model with neuroticism as an inverse predictor factor (s = −0.36, p = 0.005). We discusses that high levels of neuroticism at baseline can predict lower aggression response to fluoxetine, perhaps due to the relationship of both disorders with serotonergic dysfunction. Conclusions We can conclude that neuroticism is a relevant predictor of impulsive aggression response to treatment with SSRIs in BPD.

Treatment of impulsive aggression in correctional settings

This article reports the implementation of Dialectical Behavioral Therapy-Corrections Modified (DBT-CM) for difficult to manage, impulsive and/or aggressive correctional populations. Participants were English-speaking women (n = 18) and men (n = 45) of diverse cultural backgrounds between the ages of 16 and 59 years old retained in state-run prisons in Connecticut. Following consent, and a psychological assessment battery, twice-weekly DBT-CM groups were held over 16 weeks followed by random assignment to DBT coaching or case management condition, with sessions taking place individually for eight weeks. Data analysis. A mixed effects regression model was used to test the hypotheses: participants will show decreased aggression, impulsivity, and psychopathology, as well as improved coping, after completing the DBT-CM groups; and will show greater reduction in targeted behaviors than those receiving case management at the six month and 12 month follow-up assessment periods. Significant reduction in targeted behavior was found from baseline to following the 16 week DBT-CM skills treatment groups. Both case management and DBT coaching were significant at 12 month follow-up. A significant difference was found for adult men and women. The study supports the value of DBT-CM for management of aggressive behaviors in prison settings.

Language and the Modulation of Impulsive Aggression

The current conceptualization of the functional anatomy of impulsive aggression relies on data largely derived from studies of animal models of defensive rage. However, animal models cannot account for the replicable findings of verbal impairments and abnormalities in the language processing regions of the brain, described in more recent studies of impulsive aggression in humans. The authors present an updated model of impulsive aggression that preserves the core defensive rage functional anatomy while implicating the brain regions associated directly and indirectly with language processing and their relationship to executive function as integral to the etiology, modulation, and treatment of impulsive aggression.

Guideline Watch: Practice Guideline for the Treatment of Patients With Borderline Personality Disorder

Since the 2001 publication of APA’s Practice Guideline for the Treatment of Patients With Borderline Personality Disorder (1), more studies have been published on borderline personality disorder (BPD) than on any other personality disorder (2, 3). New analyses of the validity of the DSMIV-TR criteria–defined construct of BPD have been published, new data on the prevalence of BPD are available, risk factors for and biological characteristics of BPD are being elucidated, and new studies on the treatment of BPD have been carried out. This guideline watch highlights the most important of these developments.

A Comparison of Anticonvulsants in the Treatment of Impulsive Aggression.

This study compared the behavioral effects of 3 anticonvulsants in impulsive aggressive men. In a double-blind, placebo-controlled, parallel groups design, participants were randomly assigned to 1 of 4 6-week treatments: phenytoin (n = 7), carbamazepine (n = 7), valproate (n = 7), or placebo (n = 8). The efficacy measure was the average aggression score, a global severity index from the Overt Aggression Scale (J. M. Silver & S. C. Yudofsky, 1991). Analysis showed a significant reduction in impulsive aggression during all 3 anticonvulsant conditions compared with placebo. However, the treatment effect during carbamazepine administration was slightly delayed compared with phenytoin and valproate. These findings suggest that increased use of anticonvulsants could make a significant impact in the control of impulsive aggression in both mental health and criminal justice settings.

Commentary: Aggression and impulsivity after head injury

The most taxing behavioural complications of severe head injury for relatives include irritability and aggression, as illustrated by J. B. Longitudinal studies show an increase over time in the frequency and severity of temper outbursts (Brooks et al, 1986; Hall et al, 1994), which take the form of explosive or impulsive aggression. I will comment on the nature and treatment of impulsive aggression as illustrated in case J. B., emphasising the interaction of neurobiology with motivational, situational and personality factors.

Signs and Symptoms in Psychiatry

Signs and Symptoms in Psychiatry

The deliberate self-harm syndrome.

Recent research has differentiated several distinct classes of self-destructive behavior. This paper describes the clinical characteristics of one class, the deliberate self-harm syndrome. Analysis of 56 published case reports of self-harm revealed a typical pattern of onset in late adolescence, multiple recurrent episodes, low lethality, harm deliberately inflicted upon the body, and extension of the behavior over many years. Since the clinical characteristics of the deliberate self-harm syndrome differ substantially from those of other classes of self-destructive behavior, the authors propose that DSM-IV classify deliberate self-harm as a separate diagnostic syndrome.