Psychosis associated with epilepsy: Challenges and opportunities in developing countries

Journal:
January-June 2008 Volume 5(1)

Editorial

Author(s):
Saeed Farooq
Page No:
1
Developing countries bear more than 90% of the total burden of disease caused by epilepsy worldwide as estimated by Disability Adjusted Life Years1. About 80-98% of patients suffering from epilepsy in the developing countries are untreated1,2. The discrimination, stigma and ignorance about the disorder are widely prevalent in developing countries. A recent survey from Turkey showed that 70% of people thought that epilepsy resulted from supernatural causes2. The prospects of marriage for a girl suffering from epilepsy are often bleak in our country.

Now consider someone having two disorders epilepsy and psychosis, both associated with the worst stigma. People suffering from epilepsy have an increased risk of suffering from psychotic symptoms3,4. The prevalence of schizophrenia in people with epilepsy varies between 3% and 7% (prevalence in the general population is 1%)4. In Iceland a case controlled study found that although there was no excess of psychiatric illness in people with epilepsy, among those who were psychiatrically ill a disproportionate number were suffering from psychotic disorder5. Two national inpatient registers for epilepsy and for psychosis respectively were used to compare the subsequent incidence of schizophrenia in people who had at some point undergone admission to hospital for epilepsy with that in the general population6. A standardized incidence ratio of 1.48 for all epilepsy and 2.35 for temporal lobe epilepsy was found which suggests epilepsy as a risk factor for schizophrenia. These studies have many methodological limitations, such as a failure to use strictly defined and internationally recognized diagnostic criteria for schizophrenia and samples drawn from the neurology facilities which are not representative of the prevalent population with epilepsy. However, the results do indicate the considerably heightened risk for psychosis in patients with epilepsy.

Since clinical seizures are the outstanding feature of epilepsy, psychotic syndromes have generally been classified in the literature according to their temporal relationship to seizure itself, as ictal, postictal and interictal psychosis. An ictal psychosis can result from status epilepticus of a non-convulsive nature. The psychosis usually lasts for hours to days and consciousness is invariably impaired3,4. The most common association is with partial complex status. In the interictal psychosis the presence of psychotic episodes is not directly related to the occurrence of seizures. This can be either brief or chronic3. Chronic interictal psychosis closely resembles schizophrenia. Nearly half (45%) of the participants in the Slater study had a chronic psychosis7. In a 10-year follow-up study in Japan, 64% of the participants had a chronic psychosis8. Postictal psychosis is the most common form of psychosis found in people with epilepsy4. The psychosis, which comprises affective, schizophrenic, and organic symptoms, may last for up to a week. The psychotic symptoms are pleomorphic(persecutory, grandiose, referential, somatic, and religious delusions, catatonia, hallucinations, etc.). The affective symptoms (manic or depressive) are often prominent9.

The treatment of epilepsy as well as psychotic symptoms is very challenging. In patients treated with therapeutic doses of the more commonly used antidepressants and antipsychotics, seizure incidence rates have been reported to range from approximately 0.1% to approximately 1.5% (incidence of the first unprovoked seizure in the general population is 0.07 to 0.09)10. Amongst the antipsychotics, clozapine is the most epileptogenic. Seizures are reported in 0.3% to 5% of people treated with therapeutic doses11. To complicate matters further the anticonvulsant drugs have been reported to precipitate psychosis. There are reports that zonisamide, the most commonly used add-on treatment in Japan, is associated with psychoses12. Several cases of psychosis have also been reported during add-on therapy with newer antiepileptic drugs such as vigabatrin, felbamate, lamotrigine, tiagabine, and topiramate. In addition psychosis has also been reported in association with clobazam, phenytoin, carbamazepine, barbiturates, ethosuximide and benzodiazepines13,14.

Surprisingly, however there is little reliable objective evidence for the efficacy of antipsychotic in those suffering from psychosis concomitant with epilepsy. On a systematic search of literature we could find only one randomized trial evaluating the effectiveness of an antipsychotic (Olanzapine) in patients suffering from epilepsy which enrolled only 16 patients15.

The need for RCTs in this area is much more than realized in view of the general impression that antipsychotics are generally epileptogenic drugs. This however does not seem to be born out by clinical studies, especially in those suffering from psychosis. It is reported that the use of Clozapine, arguably most epileptogenic antipsychotic was not associated with increased risk of epileptic seizures11. The use of Clozapine in six patients with epilepsy and severe psychosis suggested that none of the reported patients had an increase of their seizure frequency; in contrast, three patients had a substantial reduction of seizures12. Similarly, another descriptive study with Thioridazine in 100 institutionalized patients with epilepsy and behavioral symptoms reported that 41% of patients had reduction in seizures after the improvement of their behavioral symptoms16. It is possible that improvement in sleep, decreased stress and possible interaction of psychotropic drugs with antiepileptic increasing the levels of later could result in improvement in the seizures. These assertions however need to be tested in randomized controlled trials.

It should be possible to conduct the pragmatic randomized controlled trials recruiting those exhibiting psychotic symptoms in a specified temporal relationship with epilepsy in developing countries in view of the high prevalence of epilepsy in many developing countries. The feasibility of such trials is further enhanced by the fact that in many developing countries including Pakistan psychiatrists treat a substantial number of people suffering from epilepsy. These trials need to include the outcome measures related to seizure control such as change in the frequency and duration of seizures which remain as matter of primary concern in the clinical practice in addition to the outcome of psychotic symptoms. A recent trial from Bangladesh addressing the complex issue of treatment of childhood epilepsy with phenobarbitone is an illustration of what can be achieved in a developing country setting with limited resources but creative thinking17. Psychosis associated with epilepsy is a major challenge for clinicians and researchers. This also provides a unique opportunity for gaining insights in two complex disorders which must be taken up by clinicians and academicians in the developing countries.

REFERENCES

1. Shorvon SD, Farmer PJ. Epilepsy in the developing countries: A review of epidemiological, socio-cultural and treatment aspects. Epilepsia 1988; 29:S36-54.

2. Aziz H, Guvenar A, Akhtar SV, Hassan KZ. Comparative epidemiology of epilepsy in Pakistan and Turkey: Population- based studies using identical protocols. Epilepsia 1997; 38:716-22.

3. Sachdev P. Schizophrenia-like psychosis and epilepsy: the status of the association. Am J Psychiatry 1998; 155:325-36.

4. Toone BK. The psychoses of epilepsy. J Neurol Neurosurg Psychiatry 2000; 69:1-3.

5. Stefansson SB, Olafsson E, Hauser WA. Psychiatric morbidity in epilepsy: A case study of adults receiving disability benefits. J Neurol Neurosurg Psychiatry 1998; 64:238-41.

6. Bredkjaer SR, Mortensen PB, Parnas J. Epilepsy and non-organic non-affective psychosis. National epidemiologic study. Br J Psychiatry 1998; 172:235-9.

7. Slater E, Beard AW, Glithero E. The schizophrenia-like psychoses of epilepsy. Br J Psychiatry 1963; 109:95- 150.

8. Onuma T, Adachi A, Hisano T, Uesugi S. 10-year followup study of epilepsy with psychosis. Jpn J Psychiat Neurol 1991; 45: 360-1.

9. Logsdail SJ, Toone BK. Post-ictal psychosis. A clinical and phenomenological description. Br J Psychiatry 1988; 152:246-52.

10. Pisani F, Oteri G, Costa C, Di Raimondo G, Di Perri R. Effects of psychotropic drugs on seizure threshold. Drug Safety 2002; 25: 91-110.

11. Langosch JM, Trimble MR. Epilepsy, psychosis and clozapine. Human Psychopharmacology 2002; 17: 115-9.

12. Matsuura M, Trimble MR. Zonisamide and psychosis. J Epilepsy 1997; 10:52-4.

13. Ferrie CD, Robinson RO, Panayiotopoulos CP. Psychiatric and severe behavioural reactions with vigabatrin: a review. Acta Neurologica Scandinavica 1996; 93:1-8.

14. Sander JW, Hart YM, Trimble MR, Shorvon SD. Vigabatrin and psychosis. J Neurol Neurosurg Psychiatry 1991; 54:435-9.

15. Farooq S, Sherin A. Interventions for psychotic symptoms concomitant with epilepsy. Cochrane Database of Systematic Review. Cochrane Library 2008 (In Press).

16. Pauig PM, Deluca MA,Osterheld RG. Thioridazine hydrochloride in the treatment of behavioral disorders in epileptics. Am J Psychiatry 1961; 832-3.

17. Banu SH, Jahan M, Koli UK, Ferdousi S, Khan NZ, Neville B. Side effects of phenobarbital and carbamazepine in childhood epilepsy: randomized controlled trial. BMJ 2007; 334: 1207.