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Anticonvulsants in the treatment of aggression
Abstract
A significant number of violent acts are committed by individuals in whom central nervous system instability can be demonstrated by special electroencephalographic (EEG) activation procedures utilizing alpha-chloralose as the activating agent. Furthermore, subcortical electrograms suggest that this instability is related to a circumscribed ictal phenomenon in the limbic system. The abruptness of the aggressive act, the fact that the behavior is so often out of character for the individual and inappropriate for the situation, as well as the confusion and partial amnesia which accompany these episodes lend clinical support for the ictal hypothesis. Some anticonvulsants not only block the activated abnormalities on the EEG but also lead to dramatic clinical improvement in those individuals showing repeated and frequent aggressive behavior. For instance, in one study 46.7 percent and 53.3 per cent of the patients demonstrated activated abnormalities on no drug and placebo, respectively. When these same patients were receiving chlorpormazine or trifluoperazine, the activation rates were 60.0 per cent and 73.3 per cent, respectively. On the other hand, when these same patients were placed on a regimen of chlordiazepoxide the activation rate was reduced to 20 per cent (p smaller than or equal to .01). Another study involved severely distrubed chronically hospitalized psychotic patients whose aggressive uncontrolled outbursts relegated then not only to a locked ward, but often to isolation rooms despite high doses of phenothiazines. A regimen of chlordiazepoxide and
... 21 Anticonvulsants have been reported to be effective at minimizing the severity of these symptoms in numerous studies. [87][88][89][90][91][92] Traditionally, anticonvulsants were commonly used for treating seizures. 93 Seizures are caused by synchronized neuron populations firing abnormally and excessively. ...
Huntington’s disease (HD) is an autosomal neurodegenerative disease that is characterized by an excessive number of CAG trinucleotide repeats within the huntingtin gene ( HTT). HD patients can present with a variety of symptoms including chorea, behavioural and psychiatric abnormalities and cognitive decline. Each patient has a unique combination of symptoms, and although these can be managed using a range of medications and non-drug treatments there is currently no cure for the disease. Current therapies prescribed for HD can be categorized by the symptom they treat. These categories include chorea medication, antipsychotic medication, antidepressants, mood stabilizing medication as well as non-drug therapies. Fortunately, there are also many new HD therapeutics currently undergoing clinical trials that target the disease at its origin; lowering the levels of mutant huntingtin protein (mHTT). Currently, much attention is being directed to antisense oligonucleotide (ASO) therapies, which bind to pre-RNA or mRNA and can alter protein expression via RNA degradation, blocking translation or splice modulation. Other potential therapies in clinical development include RNA interference (RNAi) therapies, RNA targeting small molecule therapies, stem cell therapies, antibody therapies, non-RNA targeting small molecule therapies and neuroinflammation targeted therapies. Potential therapies in pre-clinical development include Zinc-Finger Protein (ZFP) therapies, transcription activator-like effector nuclease (TALEN) therapies and clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated system (Cas) therapies. This comprehensive review aims to discuss the efficacy of current HD treatments and explore the clinical trial progress of emerging potential HD therapeutics.
... Similarly, if aggression occurs in the context of post ictal states, then it is important to control fitting as well as possible. Where ictal activity exists, anticonvulsants have been shown to reduce aggressive behaviour (Monroe 1975) and this may in part explain why carbamazepine is effective. However the latter also effects the serotinergic system (see ahead). ...
Behavioural disturbance commonly complicates dementia and is associated with carer's psychiatric morbidity. This study hypothesised that behaviours specified by carers as distressing could be managed using individually designed care packages which could reduce such behaviours and improve carer mental health as compared to usual care. People with dementia (PWD) and their carers were recruited. Carers were assessed using the General Health Questionnaire and the Geriatric Mental State (GMS) if over 65, or the Clinical Interview Schedule (from which a DSM IIIR diagnosis was made) if under 65. PWD were assessed using the Mini Mental State Examination and the GMS. The Present Behavioural Examination was completed with each carer, who specified which behaviour(s) they found most distressing. Care Packages for each couple were generated by a Multidisciplinary Team (Psychiatrists, Psychologists, Community Psychiatric Nurse, Occupational Therapist, Social Worker, Pharmacist). Couples were divided into two groups: A and B. Group A care packages were implemented over sixteen weeks. Group B acted as controls. Then both groups were reassessed (reassessment 1) using the initial rating scales. Over the following sixteen weeks Group B Care Packages were implemented. Both groups were then reassessed again (reassessment 2). At reassessment 1, compared to Group B, the behaviour of Group A dementia sufferers improved significantly (p<0.001) as did the mental health of their carers (p<0.001). At reassessment 2, the behaviour of Group A dementia sufferers and the mental health of their carers remained improved. These variables were associated. The intervention received by Group B couples neither improved carer mental health nor dementia sufferer behaviour. In conclusion, behavioural complications of dementia can be reduced and this is associated with an improvement in carer mental health. Since no single intervention was significantly effective, it is likely that care packages succeeded because they were tailored to needs.
... The first reports of carbamazepine use for the treatment of behavioural disturbances date back to the 1970s (Dalby, 1971;Monroe, 1975). After these single case reports provided initial evidence of efficacy, a negative, placebo-controlled, double-blind study was published in 1982 (Chambers et al., 1982). ...
Normal brain functioning is characterized by the balance between excitatory and inhibitory neurotransmission. Gamma-aminobutyric acid (GABA) acts as the major inhibitory neurotransmitter in the mammalian brain and is found throughout the central nervous system. Ionotropic GABAA/C and metabotropic GABAB receptors, both of which mediate the effects of GABA, are also extensively distributed in the brain. As a result GABA affects numerous physiological processes. This review will briefly summarize some of the major functions of GABA, including the role of GABA in development and brain masculinization, and the effects of GABA on circadian rhythms, sleep, feeding, aggressive behavior, and learning and memory, primarily deduced from studies using GABA receptor agonists and antagonists.
... However, one large community study by Bridgers found that epileptiform discharges, specifically, were correlated with symptoms of anorexia nervosa, depression, mania, personality disorders, suicidality without depression, nonpsychotic explosive behavior, and the effects of psychotropic medications (86). Individuals displaying antisocial and aggressive tendencies have also been found to display a wide range of EEG abnormalities, including epileptiform discharges (87)(88)(89)(90)(91). Given the wide array of psychiatric symptoms and the comorbidity of psychiatric diseases with epilepsy, long term human recordings and focused behavioral studies in animals will be needed to establish any causality between these abnormal brain activities and behaviors. ...
Epilepsy is one of the most common neurological diseases, affecting up to 1% of the world population. Epilepsy remains poorly understood and there are currently no medications to cure it. Patients with epilepsy have both seizures as well as another type of abnormal activity between seizures, known as interictal spikes. Interictal spikes have thus far been poorly researched, yet growing evidence supports an important role for them in epilepsy. In this project, we first show the high variability between reviewers in marking interictal spikes on intracranial EEG, and then develop and test an automated detection method to solve this problem. Next, we use this automated detection algorithm to identify spikes on intracranial EEG in both tumor and non-tumor patients in order to determine the best spiking parameters to identify the seizure onset zone in each group. We then develop and characterize an animal model of chronic, neocortical interictal spiking to test our observations previously made in human epilepsy and to have a molecularly-accurate model on which to test new therapeutics. Finally, we show that interictal spikes are associated with behavioral changes in this animal model and that a targeted inhibitor can both prevent the development of a spiking focus and normalize behavior. ^
... 345 Zopiclone and similar agents have improved insomnia and nocturnal wandering, 346 anxiety, 347,348 and agitation 298,349 -353 arising within the context of dementia. These drugs have also been reported to improve aggression in brain disease, 354,355 psychosis, 356 -358 depression, 359,360 and apathy in schizophrenia. 361,362 Thus, szopiclone has the potential to improve a wide range of neuropsychiatric, cognitive, and motor disturbances in patients with neurodegenerative diseases. ...
In Part I of this report, the authors reviewed preclinical and clinical evidence of neuroprotection by psychotropics and proposed criteria to predict translational neuroprotection. Here, the authors review a broad array of neuroprotective mechanisms and, based on evidence reviewed in Part I, consider agents with pharmacodynamic mechanisms of action that may be associated with neuroprotection. The neuroprotective potential of the pharmacodynamic mechanisms discussed here are held in common with drugs that evidenced neuroprotective potential in Part I. The agents examined here have symptomatic utility in neurodegenerative disease neuropsychiatric disorders and combine the most promising pharmacodynamic mechanisms yet have received insufficient research to date. Modafinil, duloxetine, ziprasidone, s-zopiclone, and ramelteon are evaluated in terms of their putative neuropsychiatric symptomatic and heuristic neuroprotective disease-modifying potentials. The authors review these agents in terms of their potential for clinical neuroprotection and suggest a criterion-based research agenda for future studies of their neuroprotective potential. Further research is needed with regard to the 10 translational neuroprotective candidate criteria, neuroprotective clinical trials, the correlation of psychotropic pharmacodynamic mechanisms with neuroprotective actions, and the translational predictive utility of the proposed candidate criteria.
... CBZ's efficacy in behavioral syndromes might be related to its inhibitory effects on limbic system kindling, increased locus coeruleus firing and enhanced tryptophan levels [23]. First reports of CBZ in the treatment of emotionally disturbed patients are reaching back to the 70 s [24,25]. In the following decade some single case reports of CBZ followed showing improvements in behavioral disturbances in demented patients262728. ...
Complex psychopathological and behavioral symptoms, such as delusions and aggression against care providers, are often the primary cause of acute hospital admissions of elderly patients to emergency units and psychiatric departments. This issue resembles an interdisciplinary clinically highly relevant diagnostic and therapeutic challenge across many medical subjects and general practice. At least 50% of the dramatically growing number of patients with dementia exerts aggressive and agitated symptoms during the course of clinical progression, particularly at moderate clinical severity.
Commonly used rating scales for agitation and aggression are reviewed and discussed. Furthermore, we focus in this article on benefits and limitations of all available data of anticonvulsants published in this specific indication, such as valproate, carbamazepine, oxcarbazepine, lamotrigine, gabapentin and topiramate.
To date, most positive and robust data are available for carbamazepine, however, pharmacokinetic interactions with secondary enzyme induction limit its use. Controlled data of valproate do not seem to support the use in this population. For oxcarbazepine only one controlled but negative trial is available. Positive small series and case reports have been reported for lamotrigine, gabapentin and topiramate.
So far, data of anticonvulsants in demented patients with behavioral disturbances are not convincing. Controlled clinical trials using specific, valid and psychometrically sound instruments of newer anticonvulsants with a better tolerability profile are mandatory to verify whether they can contribute as treatment option in this indication.
... More recently a relapse-preventing effect of CBZ in bipolar affective disorders (Ballenger and Post 1978; Okuma et al 1979; Ballenger and Post 1980; Nolen 1983; Robertson 1987; Prien and Gelenberg 1989; Simhandl et al 1990; Denk et al 1991), in mania (Okuma et al 1973; Okuma et al 1975; Okuma et al 1981; Cookson 1987; Lerer et al 1987; Okuma et al 1989) and in rapid cycling affective disorder (Post et al 1984; Schifano et al 1991) have been observed. Other studies have investigated the efficacy of CBZ in behavioral disorders characterized by aggression and overactivity (Monroe 1975; Dalby 1975; Tunks and Dermer 1977; Folks et al 1982; Cowdry and Gardner 1983; Cowdry et al 1983; Mattes et al 1984; Gardner and Cowdry 1986a; 1986b; Puente 1986; Post and Weiss 1987; Fichtner et al 1990). UNCONTROLLED EXPERIMENTS AND CASE REPORTS Table I summarizes important aspects of uncontrolled studies and case reports in which CBZ has been administered, and includes brief comments characterizing the main effects of this compound on symptomatology. ...
This article reviews current literature on the clinical efficacy of carbamazepine (CBZ) administration in schizophrenic and schizoaffective psychoses. With respect to the use of CBZ in cases of aggression, overactivity and other behavioral dyscontrol syndromes, only a few, mainly open, studies have been conducted. Attention to the efficacy of CBZ in schizophrenia and related psychoses was rather late in developing, with most of the studies done since 1981. Although the results of the different controlled and uncontrolled experiments are very difficult to compare, the results generally indicate beneficial effects--particularly if CBZ is used as an adjunct to neuroleptic medication. Suggestions for future research strategies to maximize the usefulness of CBZ in schizophrenia and related disorders are given.
Schizophrenia is a complex neuropsychiatric disorder. The etiology is not fully understood, but genetics plays an important role. Pathway analysis of genetic variants have suggested a central role for neuronal synaptic processes. Currently available antipsychotic medications successfully control positive symptoms (hallucinations and delusions) largely by inhibiting the dopamine D2 receptors; however, these drugs have more limited impact on negative symptoms (social withdrawal, flat affections, anhedonia) and cognitive deterioration. Drug development efforts have focused on a wide range of neurotransmitter systems and other agents, with conflicting or inconclusive results. New drug development paradigms are needed. A recent analysis, using common variant association results to match drugs based on their transcriptional perturbation signature, found drugs enriched in known antipsychotics plus novel candidates.
We followed a similar approach, but started our analysis from a synaptic gene network implicated by rare copy number loss variants. We found that a significant number of antipsychotics (p-value = 0.0002) and other psychoactive drugs (p-value = 0.0004) upregulate synaptic network genes. Based on global gene expression similarity, active drugs formed two main clusters: one with many known antipsychotics and antidepressants, the other with various drug categories including two nootropics. We specifically recommend further examination of nootropics with limited side effects ( meclofenoxate , piracetam and vinpocetine ) for combination therapy with antipsychotics to improve cognitive performance. Detailed experimental follow-up is required to further evaluate other candidate drugs lacking an official nervous system indication, although, for at least a few of these, psychoactive effects have been reported in the literature.
Accumulating electrophysiology evidence suggests that Borderline Personality Disorder (BPD) patients, similar to many other psychiatric groups of patients, may be a heterogeneous group (Boutros et al. 2003).
Approximately 64–68 % of EEGs in psychiatric patients can provide evidence of abnormal electrical activity (Hughes and John 1999). The issue is finding out what such deviations mean diagnostically and therapeutically. Other than an abnormality pointing to a medical condition like epilepsy or encephalopathy, most of the EEG changes described in both schizophrenia and affective spectrum disorders do not carry specific diagnostic value by today’s classification systems. Hence, the elucidation and characterization of sEEG abnormalities in both psychotic and affective disorders remain rudimentary and in need of much more systematized effort. As has now been mentioned few times, much work exploring EEG deviations in these disorders utilizing the power of computer analytic technology has been published and continues to expand. The focus of the current chapter is on sEEG deviations and possible significance as well as work that remains to be performed.
The thorough understanding of the biological mechanisms contributing to habitual aggression is fundamental if effective preventive, diagnostic, and rehabilitative programs are to be developed. Electrophysiological techniques, including conventional and quantified EEG can be very helpful in advancing our knowledge of this area. Of great interest is the serious gap between a large body of literature attesting to the prevalence of EEG, and other brain imaging abnormalities, and the actual utilization of this information in diagnosing and managing individuals exhibiting such symptoms. Moreover, the dearth of more recent research in this area further deepens this gap.
Survivors of traumatic brain injury (TBI) often exhibit aggressive behaviors that can frighten, alienate, intimidate, or place stress upon their caregivers, treatment personnel, and family members. Such aggression presents a formidable barrier to the TBI survivor’s resumption of preinjury activities, roles, and status. The challenge to rehabilitation professionals and families is to discover ways of interacting with these TBI survivors that will promote learning of the prosocial behaviors necessary to support community resettlement.
At present there is a remarkable lack of controlled and sophisticated drug studies for the management of selective target sypmtoms like violent behaviour aggressiveness, anger or hostility1,2
The problem of defining aggression—and thus differentiating it from violence—has already been discussed in Chapter 2 by David Crowell and continues to be an issue throughout this book. The position taken in this chapter is that it is clinically useful to consider extreme aggression or violence as a separate category of behavior. This is based on the observation that acts of repeated or extreme personal violence that are committed with little or no provocation are truly rare, as pointed out by Evans and Scheuer in Chapter 4. Considering the opportunities for this form of self-expression, physical acts of violence against persons are unusual in adulthood and even in adolescence.
The idea of being attacked by a violent patient is probably one of the most frightening aspects of someone coming into contact with the mentally ill for the first time. After a while, such anxieties are allayed when it can be seen that such incidents are fairly uncommon; and that when they do occur they do not usually cause permanent physical harm to the staff concerned, (Priest & Woolfson, 1986, p. 184).
Understanding the biological and environmental determinants of aggressive behavior is the goal of many scientists, ranging from anthropologists to zoologists. Psychopharmacological issues and methods have contributed to and benefited from this area of research relatively recently. Before some major findings and areas of active psychopharmacological aggression research are summarized, it will be useful to refer briefly to the theoretical and methodological roots of the current work.
In order to offer an exhaustive review of the literature concerning the relationship between mental disorders and the tendency to aggressive and violent behaviour, the authors describe the studies on the prevalence of this behaviour among psychiatric patients. After a brief historical introduction and a terminological note on the conceptual boundaries of this topic, the results of the main studies performed in the last thirty years on this subject are reviewed, taking into account both clinical and prison case histories. For each study the methodologies and their limitations are illustrated, paying attention to their social and relational biases. The results of the studies on prison samples indicate a higher prevalence of mental disorders among prisoners, but the possibility of extending these observations is limited by the factors influencing this sample composition: individuals suffering from mental disorders are at greater risk of arrest as a result of the behavioural difficulties determined by the disorder itself and of deficient supportive networks. Studies in the community also show a greater frequency of aggressive and violent behaviour among psychiatric patients, expecially in the presence of alcoholism and drug abuse, both conditions that, per se, expose the abuser to conflict and criminality. A greater risk of aggressive behaviour is also described in patients suffering from psychosis, especially in the case of persecutory delusions, in patients with associated neurological impairment (spectrum of soft neurologic signs) or with abnormal brain electrical activity detectable with EEG, and in patients with disorders characterized by impulsivity. The article concludes with a detailed description of the neurobiological basis of the aggressive behaviour, with indications on the possible efficacy of drugs action on the different neurochemical systems involved. The role of serotonin in the control of impulses, a factor that apparentely influences the whole range of aggressive behaviour, is emphasized.
As part of the current trend in suicide research to focus on specific high-risk groups (1), we have been studying suicide in schizophrenia (2–7). In addition to reviewing the literature (2), we have identified risk factors (3–5), considered the influence of depression and hopelessness (6), and examined the differences between attempters and completed suicides (7). This work, along with that of Roy (8) and others (9–15), enables us to identify high-risk patients rather than to predict specific suicides (16).
This paper examines factors involved in the theory and practice of emergency sedation for behavioural disturbance in psychiatry in the mid-twentieth century, and the emergence of the concept of 'rapid tranquillisation'. The practice received little attention until the arrival of antipsychotic drugs, which replaced older sedatives and became the agents most strongly associated with the treatment of aggression and challenging behaviour. Emergency sedation was subsequently portrayed in psychiatric literature and advertising as a therapeutic and diagnosis-driven endeavour, and the concept of rapid tranquillisation emerged in this context in the 1970s. Use of non-antipsychotic sedatives, like the benzodiazepines, is barely visible in contemporary sources, and the research suggests that antipsychotics became the mainstay of rapid tranquillisation strategies because of beliefs about their specific therapeutic properties in psychosis and schizophrenia, and not because of demonstrated superiority over other agents.
Rage dyscontrol, described and defined in Part 1 of this article (this issue), presents health care professionals with difficult and invariably urgent treatment problems, since rage outbursts disproportionate to the provocation are corrosive of relationships and readily lead to institutionalization. The manifestations of dyscontrol after traumatic brain injury are described in the light of case studies, and its precipitating organic and dynamic factors reviewed. Prerequisites for effective psychotherapy with dyscontrolled clients are defined, and a variety of treatment approaches described. Finally, the medicative control of rage is considered.
Rage dyscontrol, defined as rage outbursts that are strikingly disproportionate to the provoking stimulus, ranges in intensity from verbal abuse through to episodes of sufficient violence to cause significant property damage, injury, or death to others. The emergence and current status of rage dyscontrol as a distinct clinical entity are reviewed, a typology of dyscontrol constructed, and its known organic substrates described. The dyscontrol syndrome, shown to be unrelated to temporal lobe epilepsy, is then reviewed in relation to developmental antecedents on the one hand and a known history of traumatic brain injury on the other. Finally, the likely utility of rage dyscontrol as an extenuation in criminal cases is discussed in the light of a case history. The treatment of rage dyscontrol is considered in Part 2 of the article (this issue).
Although the cognitive impairments in dementia are the defining aspect, the non-cognitive changes such as behavioural disturbance and personality change are very common and may cause great distress to the patient and the carer. This article reviews the definition, prevalence and nature of behavioural disturbance in dementia. In addition, we review assessment scales and published reports of psychological, physical and psychosocial management strategies. Finally, we present the results of a successful randomized controlled trial of an individualized intervention package for behavioural manifestations of dementia. We conclude that this approach can help alleviate some of the distressing symptoms of dementia.
Antiaggressive and pro-aggressive properties of a variety of psychotropic and other centrally effective compounds were reviewed. 1.1. Among the sedative psychotropic compounds, neuroleptics and benzodiazepine anxiolytics are the most frequently used drugs in human aggressive and violent behavior. Antiaggressive effects of lithium is an important new finding.2.2. The drug of choice for the aggressive state of children and adolescents is predominantly psychostimulants, particularly if the aggression is associated with the minimal brain dysfunction.3.3. In episodic outbursts with or without clinical seizures, anticonvulsant drugs should first be tried specifically if patients have abnormal EEG findings.4.4. Narcotics, marijuana and hallucinogenic compounds do not have any clinical significance in the treatment of aggressive syndromes.5.5. Most of the compounds with antiaggressive properties also possess pro-aggressive effects. Aggression producing effects of benzodiazepine and anxiolytics, anti-epileptics and psychostimulants can be very significant in clinical practice.
A disorder termed temporal lobe syndrome (TLS) has been identified among psychiatric patients. It consists of organic traits suggesting a temporal lobe dysfunction, subtle mental changes characteristic of the interictal phase of TLE, and most prominently of an atypical, labile, and pleomorphic psychopathology. The TLS responds to treatment with carbamazepine and often requires the addition of an antidepressant. A series of 19 patients with epilepsy and TLS were treated with carbamazepine, combined at times with valproate for a generalized seizure component, and a modest amount of antidepressant. Ten patients achieved a remission of their psychiatric disorder, coinciding with a full or near remission of seizures. Only three patients failed to show significant improvement. All six patients who did not present with seizures of temporal lobe origin achieved complete remissions, whereas only 4 of the 13 patients with TLE achieved a remission of their TLS. The TLS is viewed as a merely reactive manifestation in the former group and as part of a more chronic process (a discharging temporal-limbic focus) in the latter. Pharmacologic treatment of the TLS associated with epilepsy can be highly effective but requires a unified approach across the specialities of neurology and psychiatry.
Introduction:
Diagnosis in psychiatry remains largely subjective. Developing biological observations in psychiatric disorders into laboratory-based diagnostic tests can significantly impact diagnosis and management of these disorders. Diagnostic electrophysiological techniques are non-invasive and relatively inexpensive.
Areas covered:
In this review, the authors propose that enough knowledge has accumulated to allow the establishment of psychiatry-based clinical electrophysiology laboratories (PCELs). A brief summary of established clinical indications for electrophysiology tests, summary of highly promising technologies and a presentation of a proposed four-step approach to facilitate the translation of promising biological observations into diagnostic tests are provided. The reader should develop an appreciation of the current status of the clinical applications of psychiatric electrophysiology. The authors propose to capitalize on the widely accepted indication to rule out medical causes of psychiatric symptoms (e.g., epileptic activity) to begin developing PCELs as the equipment and skills necessary are basic to the entire discipline. The potential impact of the growing knowledge on the practice of psychiatry is explored to update clinicians and administrators as they develop laboratory and service plans.
Expert opinion:
Psychiatric electrophysiology currently plays a limited role in the diagnosis and management in psychiatry. This status is not supported by the existing literature. The underutilization of electrophysiological tests in psychiatry is propagated by the fact that the laboratories providing the service are not managed by psychiatrists. The authors propose that the first steps are to establish such laboratories and train psychiatrists to competently provide the service.
Presented the case of a 38-yr-old female with recurrent major depression and a history of self-abusive behavior from age 5 yrs. S's behavior responded to treatment with trazodone (150 mg/day), but treatment did not relieve her depressive symptoms. (PsycINFO Database Record (c) 2012 APA, all rights reserved)
Reviews the literature on the pharmacologic treatment of aggressive behavior (AB) that is frequently encountered in patients with underlying disorders such as brain injury, schizophrenia, manic depressive disorder, and personality disorders. It is argued that many studies evaluating pharmacologic treatments of AB have methodological problems. The use and extent of effectiveness of various types of drugs (e.g., anticonvulsants, lithium carbonate, antipsychotics, sedatives and hypnotics, beta blockers) are discussed. (PsycINFO Database Record (c) 2012 APA, all rights reserved)
Psychiatric disorders that are characterized by episodic symptoms, like panic or rage attacks, are strong indications to perform a complete EEG work-up. This is based on the available literature showing that some of these patients (percentages vary based on study group) will exhibit epileptiform activity in their standard EEGs. The presence of epileptiform activity in a particulalr patient must be considered when developing a BioPsycoSocial formulation for the patient's condition and when considering treatment options.
The progressive degeneration of the brain seen in dementia is often accompanied by behavioural disturbances. Aggressive behaviour is one of the most serious of these disturbances and is a common cause for psychiatric referral, admission to hospital and drug treatment. In this article, we discuss the conceptual issues associated with defining aggressive behaviour in cognitively impaired patients. We then review the aetiology, epidemiology, methods of assessment, and management of aggressive behaviour in elderly people with dementia.
Aggressive behaviour is an inescapable clinical problem confronting practitioners of medicine, neurology and psychiatry. Several drugs have been used to treat it, with limited success. Successful use of carbamazepine in the treatment of aggressive behaviour in a patient with limbic dysfunction is reported, and varieties of aggressive behaviour that respond to carbamazepine are examined. The authors suggest that carbamazepine may have a specific anti-aggressive effect perhaps due to an anti-kindling effect, but caution that double-blind studies are needed before firm conclusions are drawn.
The etiology of violent and aggressive behavior has been studied for several decades. Observations in the 1920s of human patients who manifested aggressive behavior after incurring neurological insults led researchers to explore a biological basis for the behavior. Animal research soon followed and provided the foundation for understanding this complex behavior. Efforts to use animal models of adaptive aggressive behavior to explain pathological aggression in a subgroup of the human population has proven to be a daunting task. The research has produced a vast database encompassing several distinct disciplines. Predatory and affective aggression garners support as a classification system from clinical, social, biopsychological and forensic databases. This article draws together this vast research and delivers an argument for a bimodal classification system of aggressive and violent behavior.
Aggression may be part of a variety of psychiatric diagnoses. The appropriate treatment requires that the physician recognize the underlying cause. Pharmacologic agents may form part of the overall treatment of the patient. The number of possible drugs for treating aggression has expanded rapidly, and it is important that the physician be familiar with the various options avilable.
Background:
Aggression is a major public health issue and is integral to several mental health disorders. Antiepileptic drugs may reduce aggression by acting on the central nervous system to reduce neuronal hyper-excitability associated with aggression.
Objectives:
To evaluate the efficacy of antiepileptic drugs in reducing aggression and associated impulsivity.
Search strategy:
We searched CENTRAL, MEDLINE, EMBASE, CINAHL, PsycINFO, metaRegister of Controlled Trials (mRCT) and ClinicalTrials.gov to April 2009. We also searched Cochrane Schizophrenia Group's register of trials on aggression, National Research Record and handsearched for studies.
Selection criteria:
Prospective, placebo-controlled trials of antiepileptic drugs taken regularly by individuals with recurrent aggression to reduce the frequency or intensity of aggressive outbursts.
Data collection and analysis:
Three authors independently selected studies and two authors independently extracted data. We calculated standardised mean differences (SMDs), with odds ratios (ORs) for dichotomous data.
Main results:
Fourteen studies with data from 672 participants met the inclusion criteria. Five different antiepileptic drugs were examined. Sodium valproate/divalproex was superior to placebo for outpatient men with recurrent impulsive aggression, for impulsively aggressive adults with cluster B personality disorders, and for youths with conduct disorder, but not for children and adolescents with pervasive developmental disorder. Carbamazepine was superior to placebo in reducing acts of self-directed aggression in women with borderline personality disorder, but not in children with conduct disorder. Oxcarbazepine was superior to placebo for verbal aggression and aggression against objects in adult outpatients. Phenytoin was superior to placebo on the frequency of aggressive acts in male prisoners and in outpatient men including those with personality disorder, but not on the frequency of 'behavioral incidents' in delinquent boys.
Authors' conclusions:
The authors consider that the body of evidence summarised in this review is insufficient to allow any firm conclusion to be drawn about the use of antiepileptic medication in the treatment of aggression and associated impulsivity. Four antiepileptics (valproate/divalproex, carbamazepine, oxcarbazepine and phenytoin) were effective, compared to placebo, in reducing aggression in at least one study, although for three drugs (valproate, carbamazepine and phenytoin) at least one other study showed no statistically significant difference between treatment and control conditions. Side effects were more commonly noted for the intervention group although adverse effects were not well reported. Absence of information does not necessarily mean that the treatment is safe, nor that the potential gains from the medication necessarily balance the risk of an adverse event occurring. Further research is needed.
Recent research into mammalian cortical neurophysiology, after 6 decades of Berger's seminal work on electroencephalography, has shifted the older concept of interictal epileptiform activity (IEA) away from that of a mere electrographic graphoelement of relevance to diagnostic implications in epilepsy. Instead, accumulating information has stressed the neuropsychological implications, cognitive and/or behavioral consequence of these electrophysiological events, which are the phenotypic expression of aberrations of actual biophysical cellular function.
We feel that this review is germane to neuropsychiatry, however, a rather neglected area of research. There is a great scope for brain-behavior-EEG research in the future that can be complimented by other techniques of “neurobehavioral electrophysiology.” This review does not address the “pearls, perils and pitfalls” in the use of EEG in epilepsy, but critically and systematically reappraises the published electroencephalographic correlates of human behavior. We reiterate that epileptiform and other paroxysmal EEG dysrhythmias unrelated to clinical seizures do have neuropsychological, cognitive and/or behavioral implications as seen in the various neuropsychiatric and neurobehavioral disorders discussed in this article. IEA and EEG dysrhythmias should neither be ignored as irrelevant nor automatically attributed to epilepsy. The relevance of these EEG aberrations in the disorders of the brain-mind interface extend beyond epilepsy, and may be an electrophysiological endophenotype of aberrant neuronal behavior indicative of underlying morpho-functional brain abnormalities.
Magnetoencephalography (MEG), data fusion models (EEG-fMRI-BOLD), transcranial magnetic stimulation (TMS), evoked potentials (EP); intracranial electrophysiology, and EEG neurofeedback complemented by current functional neuroimaging techniques (fMRI and PET) would certainly help in further understanding the broader relationship between brain and behavior.
Interictal spikes (IIS) are paroxysmal discharges commonly observed in patients with epilepsy which represent an abnormally-synchronized population of hyperexcitable neurons firing as an aggregate. Due to conflicting studies on the clinical significance of IIS, research focusing on IIS has been sparse. However, recent attention on IIS has increased for patients undergoing surgery for intractable epilepsy as a means to identify epileptic foci for surgical resection. There is growing evidence that IIS are not asymptomatic as has been commonly accepted. Other than epilepsy, IIS have been associated with a wide range of behavioral and psychiatric disorders, including attention deficit disorder, anxiety disorders and psychoses. For these reasons, a well-characterized animal model of interictal spiking which accurately mimics the human phenomenon would be a valuable tool to gain, insights both into the pathophysiology of epilepsy as well as a broad variety of human neuropsychiatric diseases. Here, we review the literature on the clinical significance of IIS in humans and on animal models where IIS has been observed. We then demonstrate the utility of using tetanus toxin to generate a reproducible pattem of progressive IIS for future studies into their clinical significance.
AbstractRepeatedly violent behavior exists as a distinct behavioral syndrome with neurological, psychiatric, and environmental determinants. Neurological damage (electroencephalographic abnormalities, epilepsy, symptoms of psychomotor seizures, and a history of events known to predispose to brain injury) is prevalent. Paranoid ideation is common, too, which, with genetic evidence, links this syndrome with schizophrenia. The association of disrupted family life with episodic violence has been repeatedly confirmed. No form of therapy has been proven to be effective, but by the end of the fourth decade about half “mature” out of their previous antisocial behavior patterns.
Episodic dyscontrol (rage) was diagnosed from the clinical history, electroencephalographic findings, and response to oral treatment with phenobarbital in 3 dogs. Clinical features included a mood change heralding aggressive incidents, explosive aggression directed at people or objects, and a postaggressive phase characterized by lethargy and lack of responsiveness. Abnormal electroencephalographic findings included spike activity in the temporal recordings. All 3 dogs responded well to anticonvulsant medication with phenobarbital.
The relationship between psychiatric symptoms that respond to anticonvulsants and epileptic activity is still debated. Evidence linking electroencephalographic changes to treatment response is scarce and controversial, partly because of the poor scalp representation of limbic electrical activity. We studied the clinical relevance of focal topographic changes in the resting EEG, the visual evoked potential and the P300 response in 90 psychiatric patients, by evaluating response to anticonvulsants and development of neurological complications. The group with focal changes was compared to a group with epileptiform activity but no focal changes and a group with normal or diffusely altered EEG. Focal EEG and EP changes predicted good response to anticonvulsants, while the presence of epileptiform activity did not. Clinical seizures developed only in patients with focal changes and no anticonvulsants medication. Structural abnormalities and selective neuropsychological deficits were seen only in the focal group. There was an association of symptom type and the site of focus. We concluded that focal EEG and EP changes in psychiatric patients have important theoretical as well as practical implications.
The characteristics of all the patients admitted to a high-dependency mental handicap ward over a 21-month period were examined. The patients that had been responsible for acts of violence on the ward were compared with those who had not. Violent patients were significantly younger and more likely to have an abnormal electroencephalogram. Meningoencephalitis as the aetiology of mental handicap was over-represented in the violent group. The level of violence was alarmingly high with 620 violent incidents over 21 months (30 per month). Four patients accounted for 74% of the violence and two of these four patients suffered sudden, unexpected deaths. The relationship between violence and sudden death is examined, and the implications of pharmacological intervention with anticonvulsants for violent patients with abnormal electroencephalogram results are discussed.
Head trauma in our society is a common occurrence, resulting in significant expenditure of societal resources. Psychiatric consequences following the injury may be the cause of significant disability during the recovery process. While nearly any psychiatric symptom or disorder may occur following head injury, there are a few common complications which are reviewed in this article. Biopsychosocial factors reported to play a role in the etiology of post-traumatic psychiatric dysfunction are reviewed, diagnostic issues are discussed, and new findings regarding treatment are reviewed.
Short-term management of the agitated patient involves the use of psychological, behavioral, diagnostic, and pharmacologic options. Knowledge of verbal interventions may help physicians prevent personal injury and destruction of property. Accurate diagnosis allows safe and effective pharmacologic intervention. Involuntary treatment in emergency situations is legal; however, clearly documenting all clinical events is essential.
This is a 38- to 57-month follow-up of 50 patients referred for drug-activated electroencephalograms (EEG) because of the suspicion that a limbic complex partial seizure was a crucial mechanism behind their episodic behavior. Hence, an anticonvulsant regimen might be an effective therapeutic option. The primary referral diagnoses were intermittent explosive disorder (N = 33) panic disorder (N = 6), or formes frustes of epilepsy (N = 11). None of the patients had a significant history of typical seizures and previous routine EEGs had all been normal. Twenty nine patients also had a second axis I and three a second axis II diagnosis. On the basis of EEG findings, as well as a symptom checklist of dyscontrol behavior and a history of episodic disorders, I recommended an anticonvulsant regimen in 39 patients; this was initiated by the referring psychiatrist in 25. Of the 11 patients for whom no anticonvulsant was recommended, three were nevertheless placed on such a regimen. At the end of the follow-up period, 12 patients were still on this regimen, eight were on other regimens that probably raised seizural thresholds, and 10 were treated with antidepressants, antimanic, antipsychotic, or anti-anxiety medications. Twenty were not receiving any medication. An analysis of the diagnostic procedure and the response to the various regimens, including psychotherapy, did not demonstrate any reliable data that would aid the clinician in selecting the appropriate regimen. However, of the 20 patients on regimens that raised seizural threshold, 10 reported marked and six reported moderate improvement.
Coma and the etiology of violence are explored by the author through a review of the literature. Animal studies, post-traumatic psychic disorder studies, post-traumatic anger and violence studies, tumor and lesion of the limbic system studies, temporal lobe epilepsy studies, and episodic dysfunction syndrome studies, minimal brain studies are reviewed in Part 1 of this article. Part 2, to be published in a later issue of the journal, will conclude the review with clinical surveys on violent individuals and studies on clinical treatment of violence.These studies reveal the etiologic significance of central nervous system dysfunction in the production of violent behavior. Because central nervous system factors are involved in some instances of violent behavior, physicians clearly have a role in the early identification of potentially violent subjects and in the intervention or treatment of individuals who have been violent toward others. Studies have consistently found that lower socioeconomic groups are more predisposed to brain injury from trauma, and several studies have indicated that this is true for segments of the black community. Therefore, investigations in the relationship between central nervous system injury and violence should be a major goal of the black community. Black physicians should assume a lead role in these inquiries and in the prevention and treatment of violence, specifically black-on-black murder.
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