The treatment of agitation during initial hospitalization after traumatic brain injury. Propranolol treatment of assaultive patients with organic brain disease. A double-blind crossover, placebo-controlled study. Therapeutic effects of pindolol on behavioral disturbances associated with organic brain disease: a double-blind study. Cognitive and behavioural efficacy of amantadine in acute traumatic brain injury: an initial double-blind placebo-controlled study. Treatment of behavioral problems with pindolol. Effect of methylphenidate on brain injury-related anger.
Agitation after traumatic brain injury is disruptive for patient care, distressing, and difficult to treat. The use of propranolol has been advocated to control agitation after brain injury. It reportedly lacks some of the deleterious cognitive and emotional effects of other medications and physical restraints. This study was designed to test if propranolol is effective in reducing agitated behavior. Subjects had traumatic closed-head injury treated at a combined Level I Trauma Center and Rehabilitation Center. Twenty-one subjects met the criteria of agitation and were treated with propranolol or placebo in a double-blind fashion. The intensity of agitation was significantly lower in the treatment group although the number of episodes were similar. The use of restraints was also significantly lower in the treatment group. The results support the effectiveness of propranolol in reducing the intensity of agitation during the initial hospitalization after closed-head injury. A double-blind, placebo-controlled crossover study was conducted to examine the effects of long-acting propranolol in the treatment of violent behavior associated with organic brain disease in 10 patients whose symptoms had proved refractory to various conventional medications. Long-acting propranolol treatment was associated with reductions of assaultive behavior without apparent sedative effects. Cautions are noted regarding potential undesirable side effects which may necessitate careful patient monitoring during treatment. A double-blind, placebo-controlled crossover study was conducted to examine the effects of pindolol for the treatment of 11 patients with impulsive, explosive behaviors and other emotional-behavioral abnormalities as a consequence of brain disease or injury. Pindolol treatment was associated with significant therapeutic benefits without sedation and without the use-limiting side effects that occur with propranolol. The objective of the current study was to determine the efficacy of amantadine in improving cognitive and behavioural performance in a traumatic brain injury (TBI) rehabilitation sample. The design was a prospective, randomized, double-blind, placebo-controlled, crossover design. Subjects were 10 adult traumatic brain injury patients in an acute brain injury rehabilitation unit. Subjects received a 2-week trail of amantadine or placebo, followed by a 2-week washout, then a 2-week trail of the alternative (placebo or amantadine). Neuropsychological outcome measures included orientation, attention, executive function, memory, orientation, behaviour, and a composite variable. Results of repeated measures ANOVA and regression analysis of slope/change showed a main effect of time, but no significant difference for amantadine versus placebo. In conclusion, although patients generally improved, this initial exploratory study found no differences in rate of cognitive improvement between subjects given amantadine versus those given placebo. However, the small sample size, heterogeneous population, acute time course, and large number of dependent variables limit power and generalizability. Implications are discussed for further research to better answer questions regarding efficacy of amantadine post-TBI. A study was conducted on a group of chronically hospitalized, brain-damaged male patients to assess the effectiveness of treatment with pindolol on behavioral problems. The study was conducted in two parts. The first was a double-blind, placebo-controlled analysis of the effect of pindolol on assaultive behavior, both verbal and physical. The second part was open and sought to determine whether pindolol would diminish such behaviors as resistance to care, sexual preoccupation, or provocation of others, which were sufficient to preclude placement at a lower level of care. These target behaviors and nursing interventions were monitored and clinical global assessments of improvement in behavior and of suitability for lower levels of care were developed. Eight of 13 patients were considered improved. Those with significant premorbid personality disorders showed little benefit. Pindolol appears to ameliorate some management problems and, by inference, improve the quality of life in many patients with behavioral pathology due to organic brain disease. Anger and temper outbursts can be serious clinical problems after brain injury. This study used a randomized, pretest, posttest, placebo control group, single-blind design to evaluate the therapeutic usefulness of methylphenidate to control brain-injury-related anger. The 38 subjects in the study were young adult males who had sustained serious brain injuries and who were beyond the period of rapid, spontaneous recovery. The subjects were divided into two groups, one that received 30 mg of methylphenidate per day and the placebo control group. A comparison of the drug group with the placebo group before and at the end of the six-week treatment period on all the anger outcome measures analyzed simultaneously with multivariate analysis indicated a significant drug-by-time interaction effect, F(4.33) = 5.29, p = .002, demonstrating the therapeutic effect of methylphenidate on anger. The study found that drug responders could be predicted by pretreatment level of anger with a .09 probability of misclassification. Methylphenidate also significantly reduced impairment on all of the general psychopathology outcome measures (F[3.31] = 5.42, p < .01). The drug improved memory for those subjects in the treatment response group but did not result in changes on measures of attention, nor did it have an effect on a checklist of subjective side effects, suggesting that it has minimal or absent cognitive toxicity and is likely to be tolerated well by individuals with brain injuries.
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.