By X. Hengley. North Greenville University. 2018.

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In the first study directly comparing glucose The rational clinical psychopharmacology of aggressive be- havior began in the mid-1970s with the first placebo-con- metabolism after FEN and placebo in personality-disor- trolled buy generic baclofen 10 mg on line muscle relaxant flexeril, double-blind order baclofen 10mg line spasms above ear, study of lithium carbonate in prison dered patients with impulsive aggression, neurologically inmates (9). In this study, impulsive, but not premeditated normal subjects showed increased metabolism in orbital (or other antisocial behavior), aggression was reduced to frontal and adjacent ventral medial frontal cortex as well as extremely low levels during a 3-month course of treatment cingulate and inferior parietal cortex after FEN compared with lithium carbonate; levels of aggression remained un- with placebo, whereas impulsive-aggressive patients ap- changed in inmates treated with placebo. Notably, all gains peared to show significant increases only in the inferior pari- were lost within a month after a switch to placebo. Between-group comparisons demonstrated antiaggressive effect of lithium was replicated in subsequent blunted responses of glucose metabolism in orbital frontal, studies including a blinded placebo-controlled trial in hospi- ventral medial frontal, and cingulate cortex in the impulsive talized aggressive children with conduct disorder (194) and personality-disordered patients compared with the neuro- a blinded, placebo-controlled trial of 42 mentally disabled logically normal subjects. The mechanism of action for lithium in this in a study of patients with borderline personality disorder regard is unknown, but it likely includes an enhancement (191), who displayed reduced regional uptake of fluoro- of 5-HT function and a dampening of catecholaminergic deoxyglucose (relative to placebo) compared with control function. In more recent pilot data from a study of patients inhibitors and 5-HT1A agonists), anticonvulsants, typical with impulsive-aggressive personality disorders and controls and atypical neuroleptics, -blockers, and antiandrogenic that evaluated glucose metabolism after the administration agents, among others. Since the early 1990s, numerous activity such as 5-HT2A receptor number, transporter site open and blinded, placebo-controlled, studies have docu- number, and 5-HT2A receptors. Among pulsive-aggressive patients suggest reduced activation by as- the controlled trials, SSUIs have been shown to reduce ver- cending serotonergic projections on critical cortical inhibi- bal and nonassaultive physical aggression in personality-dis- tory regions such as orbital frontal and related medial frontal ordered patients selected for a history of recurrent, problem- cortex (137). Reduced serotonergic activation of these in- atic, impulsive-aggressive behavior (82), to reduce hibitory regions mediated in part through 5-HT2A recep- nonassaultive physical aggression in patients with borderline tors, but probably by other serotonergic mediators as well, personality disorder who were recruited from the commu- Chapter 119: Pathophysiology and Treatment of Aggression 1717 nity (196), to reduce anger attacks in depressed patients receptors appears to decrease aggression in animal models, undergoing a clinical trial for the treatment of aggression and this effect may explain the ability of newer antipsychotic (197), and to reduce impulsive aggression in adults with agents (which, unlike the older medications, block 5-HT2 autistic disorder (198). SSUI is presumed to underlie the antiaggressive effect in Studies suggest that the overall frequency of assaults, use of these subjects, the one study that examined 5-HT function seclusion, mechanical restraint, and chemical restraint in before treatment actually found a positive relationship be- patients with schizophrenia who are treated with clozapine tween pretreatment 5-HT function, assessed by PRL[d- are reduced over traditional neuroleptics (217). In a double- FEN] response, and improvement in aggression scores at blind study, risperidone had a greater selective effect on end of trial (199). These data suggest that SSUIs may work hostility than haloperidol or placebo in patients with schizo- best in patients whose postsynaptic 5-HT receptors are nor- phrenia (218). Finally, an open-label study of olanzapine mal, or only moderately impaired, in function. If so, other in 11 patients with borderline personality disorder reported agents that do not work primarily on presynaptic neurons significant reductions in anger (219), a finding suggesting may be necessary in patients with severe impairment of post- that the potential benefit of atypical neuroleptics in treating synaptic neurons. Such agents could include 5-HT receptor aggression may extend to nonpsychotic patients as well. Although evidence Given the potential facilitory role of the central nora- for the antiaggressive efficacy for 5-HT1Aagonists is limited, drenergic system, agents that dampen the function of this buspirone, at doses of 20 to 50 mg per day, was shown to system could be expected to have antiaggressive efficacy. More data, however, are available to sup- tive in reducing aggressive behavior in patients with organic port the antiaggressive efficacy of anticonvulsants. Propranolol has been Carbamazepine has been shown in blinded, placebo-con- shown to reduce aggressive behavior in patients with trau- trolled, trials to reduce episodes of behavioral dyscontrol matic brain injuries (220,221) or in patients with dementia markedly in borderline personality disorder (202) and to (222). Both propranolol and nadolol have been shown to reduce agitation and aggression in nursing home patients be effective in reducing aggressive behavior in chronic psy- with dementia (203), although not in children with conduct chiatric inpatients, independent of psychotic symptoms disorder (204). Phenytoin was also shown to reduce impul- (223,224). The use of these medications is limited, however, sive, but not premeditated, aggressive behavior in a blind, by hypotension and bradycardia, which can be side effects placebo-controlled, study of prison inmates (10). Dival- at the higher doses that are often used in these cases. Antiandrogens such as medroxyprogesterone disordered adolescents. Open trials also suggested that this acetate and cyproterone acetate appear to lower both deviant agent may reduce behavioral agitation and mood lability in and nondeviant sexual drive and activity in men with para- elderly demented patients (209,210) and in patients with philias, and this behavioral improvement is associated with aggression and mood lability secondary to brain trauma decreases in testosterone level (225). In addition, these agents have also been used in nonpsychotic patients to treat aggression and agitation, with SUMMARY mixed results. Thioridazine was reported to diminish impul- sive behavior in an open-label study of patients with border- The study of the pathophysiology and pharmacologic treat- line personality disorder (212), and low-dose haloperidol ment of aggression has undergone much progress since the was reported to reduce hostility and impulsivity compared 1980s.

On the other hand cheap baclofen 25mg overnight delivery spasm, his impulse control may simply have been temporarily lowered by alcohol intoxication buy baclofen 10 mg mastercard muscle relaxant without aspirin. Prevalence in the general population is 3% for men and 1% for women. In the past, the terms antisocial personality and psychopath/psychopathic personality disorder were used interchangeably. The antisocial individual is one who demonstrates behaviour of the type listed above. The psychopathic individual demonstrates antisocial behaviour, but in addition, demonstrates emotional impairment such as lack of guilt. Only 1/3 of those with antisocial behaviour meet the criteria for psychopathy (Hart & Hare, 1996). It is argued that the emotional impairment of individuals with psychopathy interferes with socialization, such that they do not learn to avoid antisocial behaviour. Borderline Pervasive pattern of instability of interpersonal relationships, self-image, and affects, and marked impulsivity. There must be at least 5 of the following:  Frantic efforts to avoid real or imagined abandonment  A pattern of unstable and intense interpersonal relationships characterized by alternating between extremes of idealization and devaluation Pridmore S. This is an entry from a note book maintained by an 18 year old female with borderline personality disorder. She is referring to feelings of distress, rather than the experience of major depressive disorder – although the two are frequently confused by patients, their parents and some doctors. She makes mention that when she cuts herself she feels “good”. Self cutting is very common in people with borderline personality disorder – it serves as a means of releasing tension/distress. She makes this statement without apparent conviction – people with borderline personality disorder frequently engage in suicidal behaviour (this is in addition to the cutting, most of which has little to do with suicide, and as mentioned, is a means of releasing tension/distress). A further abstract from the note book mentioned above. The patient was waiting at a bus stop with some people she knew when (she cannot remember why) she began to have negative thoughts. Dramatic, care eliciting, manipulative behaviour and unreasonable anger are common features of borderline personality disorder. This man did not satisfy the diagnostic criteria of borderline personality disorder. However, there were borderline, histrionic and narcissistic traits. He occasionally of cut himself when he was stressed. The arms, hands and abdomen of a man with a history of cutting. This man satisfied the diagnostic criteria of borderline personality disorder. He kept the large lesion on his left arm permanently open. The edges and even the base of the lesion were scarred and indurated. He burnt the dorsum of his right hand and there was muscle tissue loss from the extensors of his right forearm.