Do antipsychotic drugs increase seizure frequency in epilepsy patients?

https://doi.org/10.1016/j.euroneuro.2014.09.012Get rights and content

Highlights

  • In epilepsy patients with AED, APD treatment seems safe in seizure control outcome.

  • The improvement in the seizure outcome was only observed in partial epilepsy.

  • Seizure outcome did not differ on types of APD or psychiatric conditions.

Abstract

To investigate whether addition of antipsychotic drugs (APD) would increase seizure frequency in epilepsy patients who were already treated with anti-epileptic drugs (AED), we compared a one-year seizure control outcome in 150 epilepsy patients with APD treatment for psychiatric conditions and 309 epilepsy patients without APD treatment matched for ages at epilepsy onset and the baseline evaluation and types of epilepsy. The seizure frequency was recorded at the baseline (immediately before the start of APD) and after the 1st, 3rd, 6th and 12th months. The seizure outcome at each of the four follow-up points was compared with the baseline. The seizure outcome was compared between the two groups as a whole and according to the types of epilepsy (idiopathic generalized and partial epilepsies). In the APD group, the seizure outcome was also analyzed according to the types of APD (first and second generation APD and combination of first and second generation APD) and the types of psychiatric conditions (psychosis and non-psychosis). The seizure outcome was significantly better in the APD group than control group at all the four follow-up points. According to the epilepsy types, the improvement in the seizure outcome was only observed in the patients with partial epilepsy. Of the APD group, there was no significant difference in the seizure outcome according to the types of APD or the psychiatric conditions. In epilepsy patients who are already treated with AED, APD treatment seems safe in seizure control outcome for treatment of psychiatric conditions.

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.

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