If aggression is a problem in the clinical management of patients with epilepsy the most important point is to establish a correct diagnosis (Figure 7.5). A careful neurological, psychiatric and medical history and examination should be performed to answer the following questions: 1. Is there any medical condition that contributes to the aggressive behaviour such as endocrinological or immunologi-cal diseases? Is there any medication that might contribute to the aggressive behaviour? 2. What is the correct neurological diagnosis? Are there any other cerebral problems in addition to the epilepsy? 3. Are there any psychiatric diagnoses which possibly are independent of the epilepsy, like bipolar disease or antisocial personality disorder? If the epilepsy started early in life it is in fact often impossible to establish if, for example, a clinical picture that fulfils the criteria for an antisocial personality disorder has to be judged as independent of the organic brain disease indicated by the epilepsy or alternatively is an organic personality disorder. 4. Finally, a careful behavioural analysis and possibly video-telemetry should clarify if the aggressive behaviour is ictal, postictal or interictal and whether it occurs in the context of altered states of consciousness or psychosis.
Following syndromatic and possibly nosological diagnosis, treatment should be causal if possible i.e. intervening medical problems like endocrinological disorders should be treated adequately. Neurological syndromes like the epilepsy itself should be treated effectively but, as with all drugs that influence cerebral functioning, the question as to whether anticonvulsants might contribute to the behavioural problem should be considered. For example benzodiazepines are well known to have paradoxical effects in a minority of patients and may cause states of arousal and aggression (Binder, 1987; Daderman, 1999; Marcus, 1995; Sheth, 1994). Likewise phenobarbital is well known to cause behavioural problems with aggres-
Medical history and exam
Neurological history and exam
Psychiatric history and exam
Behavioural analysis and diagnosis of aggressive syndrome (ictal, postictal, interictal)
Treatment of medical, neurological and psychiatric condition (look for depression and anxiety)
Possibly avoid tricyclic antidepressants
Possibly avoid convulsant antipsychotics
Consider paradox side effects
Consider psychotherapy, social support
Prophylactic Psychotherapy, social support, interventions: lithium, SSRIs, antipsychotics
Management of Benzodiazepines, acute aggression: antipsychotics
Figure 7.5. Therapeutic guidelines for the treatment of aggression in patients with epilepsy.
sion in a considerable subgroup of patients with epilepsy often with learning disability (File, 1990). Besides, in individuals any given drug might have different effects than those described in large groups and thus a careful behavioural analysis of the sequence of events is the only way to establish any possible side effect, for example of antiepileptic drugs.
Care should be taken to establish signs of depression or anxiety, since a close link between these psychopathological states and affective aggression in epilepsy has been established. Both should be treated medically and with psychotherapy at the same time (Goldstein, 1997; Lorenzen, 1973). Behavioural therapy in particular in patients with epilepsy and learning disability has been proven to be very effective (Davis, 1984; Holzapfel, 1998; Rapport, 1983). In the medical treatment of depression in patients with epilepsy, SSRIs or other new antidepressants like venlafaxine should be preferred to the old tricyclic antidepressants (TCA) since the latter are more likely to provoke seizures (Blumer, 1997; Lambert, 1999). In fact, an anticonvulsant effect of SSRIs is well documented in animal models of epilepsy (Browning, 1997; Lu, 1998; Pasini, 1996; Wada, 1995) and is also described in humans (Favale, 1995).
Following treatment of all medical, neurological and psychiatric conditions that may or may not contribute to the aggressive psychopathology a symptomatic treatment of the aggression is mandatory. However, this depends on whether the aggression is an ictal, postictal or interictal phenomenon.
Ictal aggression does not need symptomatic treatment but one might consider interrupting a nonconvulsive status for example with benzodiazepines. Apart from that, a patient who displays agitation and aggression during a seizure should not be restricted since defensive violence is more common in such situations and the aggressive behaviour is self-limited, as is the seizure.
The same is true for postictal confusional states, and even aggressive behaviour in the context of postictal psychosis is self-limited. However, if the aggression is severe and disturbing or self-harming, medical treatment with benodiazepines like diazepam or clobazan and/or antipsychotics, for example risperidone, olanzapine or quetiapine should be given. Good seizure control, avoiding severe complex partial or secondary generalized seizures, is the best prophylactic intervention since postictal confusional and psychotic states are more common after severe seizures.
In interictal aggression, prophylactic and acute symptomatic treatment of aggression and agitation should be differentiated. For the treatment of acute hyper-arousal-dyscontrol syndromes a combination of benzodiazepines like diazepam and antipsychotics like haloperidol or sulpiride are still the most effective and safest interventions. In cases of interictal psychosis however, the antipsychotic medication should eventually be switched to one of the atypical antipsychotic agents with little proconvulsant potential like risperidone, olanzapine or quetiapine, since these drugs are better tolerated. A good control of the psychosis is the best way to prevent aggression if it is part of the psychosis.
In the case of interictal aggressive syndromes like IED there is no well-established medical prophylactic therapy; however, there are many anecdotal reports of effective use of substances like lithium, valproate, carbamazepine, antipsychotics, beta-blockers, clonidine and even psychostimulants (Fava, 1997; Griffith, 1985; Yudofsky, 1990). However, since there are hardly any well-conducted systematic treatment studies at the moment the medical treatment still is very experimental and single-case driven. Nevertheless, in the light of the very severe burden that is put on patients and their relatives and caregivers by the sometimes devastating behavioural episodes, a systematic trial of these agents seems to justified in special cases. The use of cognitive-behaviour therapy for anger management should also be considered, either as a first-choice treatment, or combined with psychotropic drugs.
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