Elsevier

Epilepsy Research

Volume 108, Issue 4, May 2014, Pages 765-774
Epilepsy Research

Management of antiepileptic drugs following epilepsy surgery: A meta-analysis

https://doi.org/10.1016/j.eplepsyres.2014.01.024Get rights and content

Highlights

  • This is a meta-analysis of seizure outcome after AED withdrawal and after epilepsy surgery.

  • A minority of patients who are seizure-free after surgery had recurrence after withdrawal.

  • Seizure recurrence is higher for patients without AED withdrawal.

  • Patients with seizure recurrence after AED discontinuation can be managed easily.

  • Young patients with lesional temporal epilepsy are good candidates for withdrawal.

Summary

Objective

No consensus exists regarding the management of antiepileptic drugs (AEDs) after successful epilepsy surgery (ES). We performed a meta-analysis with the most relevant evidence in this topic. Our aim was to provide evidence-based estimates of results on AEDs discontinuation after ES.

Methods

We searched MEDLINE and Embase using Medical Subject Headings and keywords related to AEDs discontinuation after ES. Two reviewers independently applied the following inclusion criteria: original published research that directly compared seizure outcomes in patients having or not AEDs discontinuation after ES. Two investigators independently extracted data, resolving disagreements through discussion. A random and fixed-effect model was used to derive a pooled odds ratio (OR) for either seizure recurrence in both groups.

Results

Of 257 abstracts initially identified by the search, 57 were reviewed as full text. Sixteen articles fulfilled eligibility criteria and described outcomes in 1456 patients with AEDs discontinuation and 685 patients with no discontinuation. The odds of having seizure recurrence after AEDs discontinuation was 0.39 times lower in patients with attempted discontinuation after surgery (OR 0.39, CI 95% 0.300–0.507, p < 0.001). Most likely the difference is related with a selected population where discontinuation was attempted.

Significance

Seizure recurrence was higher for patients without AED modification than for the withdrawal group. Patients with seizure recurrence after discontinuation can be managed easily after re-start of medications. The discontinuation of medications should be done in good candidates and the decision should be individualized taking into account clinical, electrographical, imaging and histopathological variables.

Introduction

The safety and efficacy of epilepsy surgery (ES) for temporal lobe epilepsy (TLE) has been well established in two randomized clinical trials (RCTs) (Engel et al., 2012, Wiebe et al., 2001), as well as their sustained beneficial effects in the long-term, such as prolonged seizure freedom (Téllez-Zenteno et al., 2005), lower mortality, improved psychosocial and memory outcomes (Téllez-Zenteno et al., 2007), and improved quality of life (Mohammed et al., 2012). Potential reduction and eventual withdrawal of antiepileptic drugs (AEDs) is one of the most difficult therapeutic challenges after successful ES. There are legitimate reasons to stop AEDs after ES, including avoiding undesirable long-term toxicity, to reduce cognitive adverse effects of AEDs, to reduce costs and to remove daily treatment that serves as a major affirmation of the sick role in patients (Cole and Wiebe, 2008). Compared with other surgical outcomes such as the seizure outcome, few studies have been published regarding the management of AEDs after ES and current recommendations are based largely on local experience at different centers. The selection of candidates for AEDs withdrawal is complex and we do not have uniform criteria across epileptologists and epilepsy centers.

According to three medical surveys (Berg et al., 2007, Swisher and Sinha, 2013, Téllez-Zenteno et al., 2012) of clinical practice regarding AEDs withdrawal, the majority of US and Canadian epileptologists and neurologists prefer to wait between six months to two years before any change in medication. AEDs levels, electroencephalogram (EEG), and a magnetic resonance imaging (MRI), are typically done before stopping AEDs (Berg et al., 2007, Swisher and Sinha, 2013, Téllez-Zenteno et al., 2012). The most important factors considered by epileptologists in North America were the following: focal pathology, complete postoperative seizure freedom, complete resection of a well-defined epileptic lesion, lack of postoperative epileptiform discharges on EEG, a patient's desire to stop medications and a temporal localization for the surgery (Berg et al., 2007, Téllez-Zenteno et al., 2012). Although successful AEDs withdrawal has been associated with improvements in scales of general satisfaction and quality of life, some studies have shown controversial information.

We performed a systematic review and meta-analysis of the evidence comparing seizure recurrence in patients with and without AEDs discontinuation after successful ES. Our aim was to provide clinicians with a scientifically valid and coherent summary of the best current evidence, and to provide a best estimate of seizure recurrence rates in patients with and without AEDs discontinuation after ES.

Section snippets

Data source

A medical librarian performed a comprehensive literature search of the Medline®, Embase®, Index Medicus®, and Cochrane databases from January 1980 to July 2013 that incorporated Medical Subject Headings and text words for literature on the management of AEDs after ES (Literature search strategy in Appendix A). We also searched bibliographies of reviews, original articles and book chapters, and consulted experts about other studies. We included studies if they contained original research

Evidence base

The literature search yielded 257 citations, of which 57 (22%) were potentially eligible and were examined in full text independently by two reviewers (Fig. 1). Twenty-five studies met our inclusion criteria for the meta-analysis. Twelve (48%) studies described TLE surgery patients, 12 (48%) temporal and extratemporal surgical cases and one (4%) described only extratemporal lobe epilepsy surgical patients. Overall, 90% (95% CI 89.6, 90.6) of the surgical cases were TLE cases. Ten studies (40%)

Discussion

Once seizure freedom is achieved with surgery, patients and clinicians must carefully ponder whether to taper or discontinue AEDs after successful ES. Unfortunately, the evidence is not robust and there is no consensus about management of AEDs in patients after ES (Jehi, 2013). Seizures recur whether patients are taking AEDs or not (Cole and Wiebe, 2008), and it is difficult to estimate the weight of each variable such as the clinical characteristics, EEG and MRI findings, type of surgery,

Conclusion

Our study delivers important information; a minority of patients (one in five) postoperatively seizure-free has a seizure recurrence after AED discontinuation. Patients with seizure recurrence after discontinuation can be managed easily after the re-star of medications. The discontinuation of medications should be performed in good candidates and the decision should be individualized taking into account clinical, electrographical, imaging and histopathological variables. Future research in the

Disclosure

Dr. Tellez receives grants from the University of Saskatchewan, UCB Canada and the Royal University Hospital Foundation, Saskatoon, Saskatchewan, through the Mudjadik Thyssen Mining Professorship in Neurosciences. Dr. Ladino and Dr. Hernandez-Ronquillo have nothing to disclose.

Acknowledgment

We would like to thank Richard Zhu for his help in the literature search.

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