Treatment of interictal psychiatric disorder in epilepsy. III. Personality disorder, aggression and mental retardation

Authors


C.M. van der Feltz-Cornelis, Psychiatrist/Epidemiologist, Vrije Universiteit Amsterdam, Department of Psychiatry, GGZ Buitenamstel Locatie Valeriusplein, Valeriusplein, 1075 BG Amsterdam, the Netherlands. Tel: + 31 20 5736640; Fax: + 31 20 5736687; E-mail: christif@ggzba.nl

Abstract

Background: Personality disorder, mental retardation and aggression are frequently encountered therapeutic problems in epilepsy patients.

Objective: This paper gives an overview of symptomatology and treatment of personality disorder, interictal aggression and mental retardation in epilepsy.

Methods: Literature review supplemented by clinical experience.

Results: Personality changes in patients with epilepsy are often symptoms of an organic psychosyndrome. Aggression is not more frequent among epilepsy patients than in the general population, but if it does happen it is often more severe. There is a need for controlled treatment studies. A treatment strategy is suggested. In the mentally retarded, diagnostic instruments should be used to overcome diagnostic difficulties.

Conclusion: Prevalence studies based on DSM-IV personality disorder, conducted in the community, are needed, as well as systematic research on diagnosis and treatment of personality disorder in epilepsy patients. Randomized controlled trials (RCTs) considering the effectiveness and adverse effects of antidepressants and neuroleptics in epileptic patients with mental retardation are seriously needed. In the meantime, the Expert Consensus Guideline Series on Treatment of Psychiatric and Behavioural Problems in Mental Retardation is useful. The use of neuroleptics for the treatment of aggressive or destructive behaviour in nonpsychotic mentally retarded patients remains controversial.

Introduction

In the literature (1) as well as in research, a link has been made between epilepsy, certain personality traits, mental retardation and aggression. There are many case reports from forensic psychiatry in this area. Also, multiple personality disorder patients with pseudo-seizures are a welcome subject of forensic research. Dissociative disorders can be a comorbid condition as well as a differential diagnostic consideration in patients with epilepsy. Because of the complexity,this topic will not be addressed in this paper. Kuyk and colleagues have elaborated on this (2). However, the intricate connections between personality disorder, mental retardation, epilepsy and aggression are of clinical relevance in the treatment of epilepsy patients. This paper will give an overview of recent research on prevalence, symptomatology and treatment of personality disorder, interictal aggression – interictal in the sense suggested by Pond (3) – and mental retardation in adult epilepsy patients who reside in epilepsy centres or who receive out-patient care.

Method

A MEDLINE search was performed using the MESH keywords epilepsy, psychiatry, personality disorder, aggression, psychotropic medication, mental retardation and treatment. This search yielded 198 results. A search for randomized controlled trials (RCTs) on these topics yielded no results. Therefore, open studies, transverse studies, casenote studies, surveys and reviews were taken into account, with a focus on in vivo research, treatment and interictal disorder. This reduced the original 198 findings to 30 papers and one treatment guideline. The present paper gives an analysis of these and draws on clinical experience when research is missing.

Personality disorder

Psychopathology

Geschwind syndrome. Much has been written on the subject of personality change. Benson (4) gives an overview of the ‘Geschwind syndrome’, a characteristic personality syndrome in epilepsy patients that is still the subject of ongoing controversy, consisting of:

  • • circumstantiality − excessive verbal output, stickiness, hypergraphia;
  • • altered sexuality – usually hyposexuality; and
  • • intensified mental life – deepened cognitive and emotional responses.

It has been suggested that this syndrome exists especially in treatment-refractive temporal lobe epilepsy, and could subside after classical temporal lobectomy, especially if reduction of seizures was attained as well by the surgical treatment (5). Benson suggests that carefully directed research is needed to substantiate symptomatology and possible pathophysiological mechanisms as an answer to criticisms of the concept.

Organic psychosyndrome.  These criticisms state that from a historical point of view, the Geschwind syndrome can be seen as an organic psychosyndrome combined with adverse effects of older antiepileptic drugs (AEDs), such as bromides and barbiturates. The above-mentioned symptoms can be attributed at least partly to this (6). Even in this time, these symptoms can be variously attributed to poorly controlled epilepsy with multiple anoxic brain damage and head traumas (7,8); to treatment with antiepileptics (9); to chronic institutionalization(leading to regression); and to social stigmatization (leading to, for example, avoidant traits). Personality changes are further associated with complex partial seizures, especially in case of hyperreligiosity. Many such personality changes, however, are not specific to epilepsy, but non-specific consequences of brain damage and as such symptoms of an organic psychosyndrome.

Personality disorder.  Are there personality disorders in the sense of the DSM-IV classification (10) in epilepsy patients? The majority of the selected papers discusses personality traits that might be classified as an organic psychosyndrome, or multiple personality disorder, now known as dissociative identity disorder. Neither are Axis II personality disorders according to the DSM-IV classification, but an Axis I disorder. Only a few prevalence studies use the personality disorder criteria according to the DSM-IV classification.

Prevalence

One study of epilepsy surgery patients did find a prevalence of 18% of personality disorders, mainly with dependent and avoidant traits (11). This is a study in a tertiary treatment centre; there is a need for community studies.

Treatment

Blumer (12) sees personality change in epilepsy patients as a continuum towards mood disorders, for which mood stabilizers can be helpful. He proposes that patients with personality changes and a mood disorder be treated with carbamazepine or valproate monotherapy, and that AEDs with sedative effects be avoided. Patients with temporal lobe epilepsy who undergo personality changes that lead to dysfunctioning or to depressive syndromes may benefit from an antidepressant agent (13).

The notion of treating certain ‘personality traits’ with psychotropic medication can be useful when the symptoms are due to medication effects of AEDs, to poorly controlled epilepsy or, alternatively, caused by an organic psychosyndrome.

It can also make sense to treat with an antidepressant in clinical settings or in patient groups, where an adequate diagnosis of depressive disorder is difficult to make. In the case of personality disorder conforming to DSM-IV classification treatment with an antidepressant would, however, be controversial, although Kramer (14) also suggested this for general psychiatry patients.

Clearly, there is a need for systematic research on treatment of personality disorder in epilepsy patients, whether it be RCTs concerning the effects and adverse effects of antidepressants or AEDs in the treatment of personality disorder in epilepsy patients, or RCTs on other treatment strategies such as group therapy, that are common to use in certain personality disorders in general psychiatry.

Interictal aggression

Predisposing factors

Interictal aggression occurs especially in young, mentally retarded males with interictal chronic psychotic disorders and long-term epilepsy (15). Temporal epilepsy is correlated more strongly with aggressive behaviour than generalized epilepsy (16,17). Phenobarbital may also play a role (8).

Prevalence

Although aggression is not more frequent among epilepsy patients than in the general population, it is often more severe; witness the fact that the epilepsy rate is two to four times higher in the prison population (8).

Treatment

Optimization of AEDs.  As RCTs are missing, the following statements are based on reviews (18), case reports, open studies and clinical experience. The first step is always to evaluate if optimization of the AEDs is necessary and possible (15). The use of lithium against aggression in epilepsy is controversial in view of the reported increases in seizure frequency (19). Carbamazepine may have favourable effects (20).

Fluoxetine. As a next step, interictal aggression can be treated with fluoxetine in case of concomitant dysphoria, depressive disorder or personality disorder (21). However, as it has been reported to interact with phenytoin, blood-level monitoring may be necessary (22).

Propanolol. Propanolol 120–350 mg a day can be administered for aggression in the case of an organic component such as frontal brain damage (19).

Neuroleptics. Neuroleptics can be given in the event of concomitant psychotic symptomatology (15). The positive effects and adverse effects of neuroleptics in epilepsy patients are described in another paper (23). It should be noted that clozapine lowers the stimulus threshold to such an extent that it is better not given to epilepsy patients (24–27).

Surgery. In the case of treatment-refractive temporal lobe epilepsy with serious aggressive and destructive behaviour, amygdalotomy has been effective in a limited number of cases, if reduction of seizures was also attained by the surgical treatment. Early referral, as soon as the failure to respond to AEDs is evident, increases the chance of success (5).

Mental retardation

Prevalence

There are several prevalence studies concerning psychiatric disorder in mentally retarded patients with epilepsy. Reid et al. (28) found a non-specified personality disorder in 22% of mentally retarded patients. Deb (29) studied the rate of mental disorder in 150 adults with mental retardation and epilepsy, who lived either in institutions or in the community, and compared them with a matched non-epileptic control group. Sixty-five per cent of the whole cohort had an ICD-9 diagnosis of mental disorder. No significant difference in the rate of mental disorder emerged between the epileptic and non-epileptic groups. Deb concludes that ‘underlying brain damage rather than epilepsy per se is a stronger determinant of psychopathology in the studied patient group’. In a retrospective review of 143 mentally retarded adults with epilepsy, Deb and Joyce (30) found psychiatric comorbidity in 12.6% of cases, of which 5% were psychotic disorders.

Symptomatology

In the case of mental retardation, establishing a diagnosis of mental disorder can be a challenge. Mentally retarded people often manifest their depressive syndromes in somatization (for instance as fatigue or regression) or in dysphoria or sudden sadness, rather than by explicitly saying that they are feeling low.

The psychoses of the mentally retarded are a good deal less sophisticated than those of psychotic patients of normal intelligence. If they hallucinate, for example, they may not report hearing voices, but instead accuse other residents of playing the radio too loud when in fact no radio is on at all. Paranoid delusions are not carried through to the level of plot theories, but the patient may instead approach everyone asking, ‘Are you mad at me?’ In an excellent review, Deb and Weston (31) discuss several diagnostic guides, assessment schedules, checklists and scales that are validated in the treatment setting of mentally retarded patients.

Principles in treatment in treatment

The importance of social intervention.  Mental retardation forms a permanent and radical constraint on personality development. The integrative function of the ego develops poorly, and this implies weakened psychological resilience, increased psychological burden and a strong influence from environmental factors on both the onset and the remission of psychiatric comorbidity. Treatment should therefore always begin by determining whether environmental factors are responsible for the patient's psychiatric symptomatology. One should be aware that seemingly minor stressors, such as a holiday of a trusted group leader, an approaching birthday or public holiday, or relocation of the patient's ward, can trigger a major psychiatric decompensation, even psychosis. On the other hand, if such a stressor is removed and the patient is again provided environmental structure, such psychiatric symptoms often disappear within a few days like snow in summer. Hence, providing structure and shielding from stressors is always the first-choice treatment strategy for mentally retarded, psychiatrically decompensated patients. Sometimes, however, a stressor cannot be removed, or the mental disorder fails to remit and is a source of dangerous behavioural disturbances.

Medication. In these cases, medicinal intervention is indicated. There are some basic rules to be followed: first, a complex issue in clinical practice is that mentally retarded patients can show extremely variable behaviour, which might be blamed erroneously on the new medication. Before prescribing any psychotropic medications, it is therefore advisable to make a full assessment of a patient's behaviour, then to begin medication, to keep score-sheets over a 6-week period, and then to use these in assessing whether the medication has the desired effect.

A second rule is that the starting and stopping of medication for mentally retarded epilepsy patients with organic brain damage must proceed much more gradually than in the ordinary psychiatric population because they are more easily brought out of balance, both somatically and emotionally. While haloperidol can be initiated in a non-epileptic psychotic patient and titrated to the right dosage within a few days' time, the same process would take weeks for a psychotic mentally retarded patient with epilepsy. The latter group is far more susceptible to side-effects such as akathisia, tardive dyskinesia and other extrapyramidal motor disturbances.

In addition, such patients are usually already taking several anti-epileptic drugs, and the pharmacokinetic interaction set off by a new agent could alter the action of the various medications, as has been seen with phenytoin (9). Blood level monitoring can sometimes be helpful, and the body needs time to adjust to the new pharmacokinetic balance (32).

In the case of depression SSRIs are effective (19), but fluoxetine is reportedly associated with an increase in impulsive aggressive behaviour. This might be attributed to akathisia, to interaction with other medications or to some specific serotonergic effect (21).

Benzodiazepines can be considered for short-term treatment of anxiety. Brain-damaged patients, in particular, can sometimes react paradoxically to drugs of this type, but the use of benzodiazepines for such patients can none the less be very effective (19,33). Antidepressants are preferable for longer-lasting conditions such as generalized anxiety disorder, and might be useful for obsessive-compulsive disorders (34).

Neuroleptics work well in cases of psychosis, especially the new atypical ones, but it is important not to give overly large doses and not to taper dosages up and down as sharply as with normally intelligent patients, to avoid setting off paradoxical reactions and a variety of adverse effects. As mentioned before, clozapine should be avoided (24–27).

In their review, Deb and Weston (31) state how the use of neuroleptics for the treatment of aggressive or destructive behaviour in mentally retarded patients remains controversial, ‘Studies are showing that it is possible, without causing behavioural deterioration, to reduce antipsychotic medications when used purely for the management of behavioural disorder in individuals with mental retardation’. They discuss other options, such as propanolol, sodium valproate and SSRIs, that unfortunately are tested mainly in uncontrolled trials, and they call for further large-scale double-blind studies specifically in mentally retarded patients.

Cognitive-behavioural therapy (CBT). CBT, with some modification, can be useful for mentally retarded patients with anxiety disorder, depression, anger and sexually deviant behaviour (35).

Expert Consensus Treatment Guideline. Although not specific for the population of patients with epilepsy, the Expert Consensus Guideline Series on Treatment of Psychiatric and Behavioural problems in Mental Retardation (36) can prove very useful.

Conclusion

Most personality changes in patients with epilepsy are not specific to epilepsy, but aspecific consequences of brain damage and, as such, symptoms of an organic psychosyndrome. In the majority of the papers selected discuss personality traits that might be classified as an organic psychosyndrome, or multiple personality disorder, now known as dissociative identity disorder. Neither is a personality disorder according to the DSM-IV classification. Population-based prevalence studies based on DSM-IV personality disorder classification in epilepsy patients are needed.

There is a tendency to see personality change in epilepsy patients as a continuum towards mood disorders, and to treat them with AEDs and antidepressants. This can be useful when the symptoms are due to an organic psychosyndrome.

Also, it can be sensible to treat with an antidepressant in clinical settings or patient groups where an adequate diagnosis of depressive disorder is difficult to make. In the case of personality disorder according to the DSM-IV classification, treatment with an antidepressant would, however, be controversial. Obviously there is need for systematic research on diagnosis and treatment of personality disorder in epilepsy patients, whether it be RCTs concerning the effects and adverse effects of antidepressants or AEDs in the treatment of personality disorder in epilepsy patients, or RCTs on other treatment strategies such as group therapy, that are used commonly in certain personality disorders in general psychiatry.

Although aggression is not more frequent among epilepsy patients than in the general population, it is often more severe. There is a need for controlled treatment studies. The following treatment strategy can be suggested: optimization of AEDs, followed by treatment with fluoxetine, propanolol or neuroleptics. Clozapine should preferably not be given to patients with epilepsy.

In treating the mentally retarded, diagnostic instruments should be used to overcome diagnostic difficulties. RCTs considering the effectiveness and adverse effects of antidepressants and neuroleptics in epileptic patients with mental retardation are seriously needed. The Expert Consensus Treatment Guideline could be used, although this guideline was not developed particularly for patients with epilepsy. The use of neuroleptics for the treatment of aggressive or destructive behaviour in mentally retarded patients remains controversial.

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