Nadolol to treat aggression and psychiatric symptomatology in chronic psychiatric inpatients: a double-blind, placebo-controlled study. Low dose beta blockade in acute stroke ("BEST" trial): an evaluation. Levetiracetam in patients with impulsive aggression: a double-blind, placebo-controlled trial. Parenteral lorazepam versus parenteral haloperidol for the control of psychotic disruptive behavior. A comparison of anticonvulsants in the treatment of impulsive aggression. Atypical antipsychotic agents in the treatment of violent patients with schizophrenia and schizoaffective disorder.
Considerable evidence indicates that the lipophilic beta-blocker propranolol is useful in treating organically based aggression. This study looked at the efficacy of a more hydrophilic beta-blocker, nadolol, to treat aggression in chronic psychiatric inpatients.
                Forty-one chronic psychiatric inpatients with an average of one aggressive outburst per week (defined by the Overt Aggression Scale [OAS]) were entered into a double-blind, placebo-controlled study lasting 17 weeks. The OAS was used to track aggression on a per-incident basis, while the Brief Psychiatric Rating Scale (BPRS) and the Clinical Global Impressions scale (CGI) were used to track clinical status.
                Nadolol subjects showed a significant decline in frequency of aggression compared with controls (p = .026) and a significant decline in the BPRS total score (p = .007) and in the subfactors "hostility and suspicion," "negative symptoms," and "signs of hyperarousal/tension." There was no significant change in CGI "severity of illness" ratings between groups, although the nadolol group was significantly improved from baseline at every subsequent time period while the placebo group was unchanged throughout the study.
                Nadolol is of significant benefit in the treatment of aggression in chronic psychiatric inpatients. This drug does penetrate the brain over time, but the success of a drug whose primary locus of action is peripheral may implicate a bimodal mechanism of action, i.e., a role for the CNS and the soma in the maintenance of aggression. The beta blocker stroke ("BEST") trial was designed to see if the apparent protective effect of propranolol on cerebral function in patients with subarachnoid haemorrhage applied also to patients suffering from acute stroke. Three hundred and two conscious patients with clinically diagnosed hemispheric strokes sustained within the past 48 hours were randomly assigned to receive atenolol, propranolol, or matching placebo capsules for three weeks. More early deaths occurred among the patients allocated to receive beta blockers, but this was largely explained by differences in the initial characteristics of the patients among the different treatment groups. By contrast, the outcome in a further 60 patients, who had been taking beta blockers at the time of their stroke but were otherwise similar to the patients in the trial, was considerably better, suggesting that prior treatment with beta blockers might be protective. The search for an effective medical treatment for acute stroke must continue. The approach used here, in which neurological outcome was assessed in a modest number of patients with a view to proceeding subsequently to a full scale trial of functional outcome, allows practical benefits of a treatment to be evaluated under realistic conditions and an ineffective treatment to be eliminated without undue cost. There are few controlled studies evaluating drug treatment for impulsive aggression. The objective of this study was to evaluate levetiracetam in patients with impulsive aggression, and whether diagnosis or other baseline characteristics predict response.
                Outpatients with clinically significant impulsive aggression (meeting Coccaro et al. revised criteria for intermittent explosive disorder), without other psychiatric symptomatology clearly requiring treatment, were randomly assigned to levetiracetam or placebo, double-blind, for 10 weeks, at a variable dose with a maximum dose of 3000 mg/day. The primary efficacy measure was change in the total aggression score from the revised Overt Aggression Scale-Modified. The study was conducted from September 2005 to July 2006.
                Of 40 patients (20 in each treatment group), 34 completed at least 4 weeks of treatment with double-blind medication. There was no overall statistical evidence of levetiracetam benefit, and no subgroup more responsive to levetiracetam could be identified.
                Levetiracetam was not as efficacious as oxcarbazepine was in a prior similar study. Additional studies of medications for impulsive aggression seem warranted. In a double-blind, prospective study, 2 mg of intramuscular lorazepam and 5 mg of intramuscular haloperidol were equally effective in controlling aggression, agitation, and assaultive behavior. Although lorazepam and haloperidol produced an equivalent mean decrease in aggression, significantly more subjects who received lorazepam had a greater decrease in aggression ratings than haloperidol recipients; this effect was independent of sedation. Lorazepam produced significantly fewer extrapyramidal symptoms. These data support the current clinical practice of using lorazepam (alone, or in combination with a neuroleptic) for control of acute aggressive and assaultive behavior. 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. Violent behavior of patients with schizophrenia prolongs hospital stay and interferes with their integration into the community. Finding appropriate treatment of violent behaviors is of primary importance.
                To compare the efficacy of 2 atypical antipsychotic agents, clozapine and olanzapine, with one another and with haloperidol in the treatment of physical assaults and other aggressive behaviors in physically assaultive patients with schizophrenia and schizoaffective disorder.
                Randomized, double-blind, parallel-group, 12-week trial. Physically assaultive subjects with schizophrenia or schizoaffective disorder who were inpatients in state psychiatric facilities were randomly assigned to treatment with clozapine (n = 37), olanzapine (n = 37), or haloperidol (n = 36).
                Number and severity of physical assaults as measured by the Modified Overt Aggression Scale (MOAS) physical aggression score and the number and severity of all aggressive events as measured by the MOAS overall score. Psychiatric symptoms were assessed through the Positive and Negative Syndrome Scale (PANSS).
                Clozapine was superior to both olanzapine and haloperidol in reducing the number and severity of physical assaults as assessed by the MOAS physical aggression score and in reducing overall aggression as measured by the MOAS total score. Olanzapine was superior to haloperidol in reducing the number and severity of aggressive incidents on these 2 MOAS measures. There were no significant differences among the 3 medication groups in improvement of psychiatric symptoms as measured by the PANSS total score and the 3 PANSS subscales.
                Clozapine shows greater efficacy than olanzapine and olanzapine greater efficacy than haloperidol in reducing aggressive behavior. This antiaggressive effect appears to be separate from the antipsychotic and sedative action of these medications.
Numerous drugs have been tried in the management of aggression in ABI but without firm evidence of their efficacy. It is therefore important to choose drugs with few side effects and to monitor their effect. Beta-blockers have the best evidence for efficacy and deserve more attention. The lack of evidence highlights the need for better evaluations of drugs for this important problem.