Do antipsychotic drugs increase seizure frequency in epilepsy patients?
Introduction
Patients with epilepsy often exhibit psychosis, psychomotor excitements or related conditions. The prevalence of psychiatric disorders in epilepsy patients is significantly higher than in the general population (Gudmundsson, 1966). As in functional psychosis in patients without epilepsy, antipsychotic drugs (APD) are often used for the treatment of psychiatric conditions in those with epilepsy (Karouni et al., 2010, Kerr et al., 2011, Adachi et al., 2013). APD have long been considered as proconvulsants (Itil and Soldatos, 1980, Oliver et al., 1982, Haddad and Sharma, 2007, Kumlien and Lundberg, 2010). Possibilities of the increase in seizure frequency have sometimes prevented physicians treating epilepsy patients with APD although there is little evidence that patients who were taking therapeutic dosages of antiepileptic drugs (AED) exhibit seizure aggravation with the treatments of APD (Ojemann et al., 1987, Alldredge, 1999, Gross et al., 2000). APD were found to lower seizure threshold in experimental conditions (Oliver et al., 1982, Melduram, 1988); de novo seizures after the administration of APD were mainly reported in patients in functional psychosis who were not treated with AED (Alper et al., 2007, Kumlien and Lundberg, 2010).
Patients with intractable epilepsy sometimes exhibit seizure aggravation during a course of the illness (Okazaki et al., 2011). Such aggravation may happen at the time of treatment with APD for their psychiatric and/or behavioral difficulties. Since the seizure aggravation is often caused by inter-related clinical factors (e.g., insomnia, fatigue, and non-compliance with AED) (Okazaki et al., 2011), it is sometimes difficult to attribute the aggravation of seizures into only the administration of APD. One way of examining the effects of the APD administration on seizure frequency is to compare patients with and without treatment of APD in a controlled manner, which has been scarce so far. In addition, our knowledge on the long-term seizure prognosis while treated with APD is limited and needs to improve because mental and behavioral problems in epilepsy patients often persist; thus long-term APD treatment is required in many cases (Adachi et al., 2013).
In this study with a large cohort of epilepsy patients who were already treated with AED, we compared seizure frequency for a one-year follow-up period between patients who recently started on APD and those without APD treatment in order to investigate effects of adding APD on seizure frequency.
Section snippets
Subjects
We reviewed consecutive records of 150 epilepsy patients who started taking APD (APD group) in the period between April 1, 1993 and December 31, 2011 at the National Center Hospital, Adachi Mental Clinic, Jozen Clinic, Tenshi Hospital, Asai Hospital, or Musashino Kokubunji Clinic. The interval of regular clinical reviews ranged from one week to three months in accordance with the national treatment guidelines; the frequency of contacts depended on the patients׳ conditions and needs. All the
Characteristics
The demographic and clinical characteristics of the patients in the APD and control groups are shown in Table 1. Between the two groups, there was no significant difference in sex, age at onset of epilepsy, age at baseline examination, duration of epilepsy, epilepsy type, baseline seizure frequency, and the number of AED taken.
In the APD group, the patients took a mean dosage of 662.7 (SD 745.5, range 30–4120) CPeq mg/day. The mean number of APD taken was 1.9 (SD 1.1, range 1–7). Seventy-two
Early seizure outcome of APD treatment
The seizure frequency in the epilepsy patients was rarely exacerbated by the addition of APD. After the 1st month, the seizure outcome was significantly better in the APD group than control group; only 2 patients with APD (1.3%) experienced an increase in seizure frequency compared to the baseline, while 13 controls (4%) experienced an increase. This finding was in line with previous two reports (Ojemann et al., 1987, Gross et al., 2000). These small case series, 13 cases in Ojeman׳s study
Conclusion
This study demonstrated that the seizure outcome in epilepsy patients improved throughout the one-year follow-up period after the administration of APD for psychiatric conditions. This was mainly observed in the patients with partial epilepsy. We did not find any particular APD or combination of APD that had a high risk to increasing seizure frequency. Our findings may suggest that our empirical approaches of APD treatment (excluding clozapine which was not available during the study period)
Role of funding source
The study was completed with no sponsorship in study design; in the collection, analysis and interpretation of data; in the writing of the report; and in the decision to submit the paper for publication.
Contribution
Author Okazaki M managed to collecting data and described the first draft of the manuscript. Author Adachi N designed the study, wrote the protocol and undertook the statistical analysis. Author Akanuma N managed the literature searches and elaborated the manuscripts. Authors Hara K, Ito M. Kato M and Onuma T treated patients and evaluated the study items. All authors contributed to and have approved the final manuscript.
The conflict of interest
None of authors has any (actual or potential) conflict of interest to disclose. There was no financial, personal or other relationships with other people or organizations within three (3) years of beginning the work submitted that could inappropriately influence, or be perceived to influence, our work. We confirm that we have read the Journal׳s position on issues involved in ethical publication and affirm that this report is consistent with those guidelines.
Acknowledgments
In the current study, no particular acknowledgment will be shown in the manuscript.
References (37)
- et al.
Seizure incidence in psychopharmacological clinical trials: an analysis of Food and Drug Administration (FDA) summary basis of approval reports
Biol. Psychiatry
(2007) - et al.
Effects of antipsychotic drugs on the duration of interictal psychotic episodes in epilepsy patients
Epilepsy Behav.
(2013) - et al.
Seizure risk associated with neuroactive drugs: data from the WHO adverse drug reactions database
Seizure
(2010) - et al.
Antipsychotics and seizures: higher risk with atypicals?
Seizure
(2013) - et al.
Seizures with neuroleptics and antidepressants
Gen. Hosp. Psychiatry
(1987) - et al.
One-year seizure prognosis in epilepsy patients treated with antidepressants
Epilepsy Behav.
(2011) Treatment of mental disorders in epilepsy patients
Jpn. J. Psychiatry Treat.
(2005)- et al.
Interictal psychotic episodes in epilepsy: duration and associated clinical factors
Epilepsia
(2012) - et al.
Predictive value of interictal epileptiform discharges during non-REM sleep on scalp EEG recordings for the lateralization of epileptogenesis
Epilepsia
(1998) - et al.
Basic treatment principles for psychotic disorders in patients with epilepsy
Epilepsia
(2013)
Seizure risk associated with psychotropic drugs: clinical and pharmacokinetic considerations
Neurology
Olanzapine-induced clinical seizure: a case report
Clin. Neuropharmacol.
Proposal for revised classification of epilepsies and epileptic syndromes
Epilepsia
A transcranial magnetic stimulation study of the effects of olanzapine and risperidone on motor cortical excitability in patients with schizophrenia
Psychopharmacology
International consensus study of antipsychotic dosing
Am. J. Psychiatry
Psychotropic medication use in patients with epilepsy: effect on seizure frequency
J. Neuropsychiatry Clin. Neurosci.
Epilepsy in Iceland
Acta Neurol. Scand.
Adverse effects of atypical antipsychotics. Differential risk and clinical implications
CNS Drugs
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