[Show abstract][Hide abstract] ABSTRACT: Introduction:
People with chronic epilepsy (PWE) often make costly but clinically unnecessary emergency department (ED) visits. Offering them and their carers a self-management intervention that improves confidence and ability to manage seizures may lead to fewer visits. As no such intervention currently exists, we describe a project to develop and pilot one.
Methods and analysis:
To develop the intervention, an existing group-based seizure management course that has been offered by the Epilepsy Society within the voluntary sector to a broader audience will be adapted. Feedback from PWE, carers and representatives from the main groups caring for PWE will help refine the course so that it addresses the needs of ED attendees. Its behaviour change potential will also be optimised. A pilot randomised controlled trial will then be completed. 80 PWE aged ≥16 who have visited the ED in the prior 12 months on ≥2 occasions, along with one of their family members or friends, will be recruited from three NHS EDs. Dyads will be randomised to receive the intervention or treatment as usual alone. The proposed primary outcome is ED use in the 12 months following randomisation. For the pilot, this will be measured using routine hospital data. Secondary outcomes will be measured by patients and carers completing questionnaires 3, 6 and 12 months postrandomisation. Rates of recruitment, retention and unblinding will be calculated, along with the ED event rate in the control group and an estimate of the intervention's effect on the outcome measures.
Ethics and dissemination:
Ethical approval: NRES Committee North West-Liverpool East (Reference number 15/NW/0225). The project's findings will provide robust evidence on the acceptability of seizure management training and on the optimal design of a future definitive trial. The findings will be published in peer-reviewed journals and presented at conferences.
Trial registration number:
ISRCTN13 871 327.
BMJ Open 07/2015; 5(e009040):1-10. DOI:10.1136/bmjopen-2015-009040 · 2.27 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Background:
This is an updated version of the original Cochrane review published in Issue 2, 2002 and its subsequent update in 2010.Epilepsy is a common neurological condition in which recurrent, unprovoked seizures are caused by abnormal electrical discharges from the brain. It is believed that with effective drug treatment, up to 70% of individuals with active epilepsy have the potential to become seizure-free and go into long-term remission shortly after starting drug therapy with a single antiepileptic drug in monotherapy.Worldwide, carbamazepine and phenytoin are commonly used broad spectrum antiepileptic drugs, suitable for most epileptic seizure types. Carbamazepine is a current first line treatment for partial onset seizures in the USA and Europe. Phenytoin is no longer considered a first line treatment due to concerns over adverse events associated with its use, however the drug is still commonly used in low- to middle-income countries due to it's low cost. No consistent differences in efficacy have been found between carbamazepine and phenytoin in individual trials, however the confidence intervals generated by these studies are wide. Therefore, differences in efficacy may be shown by synthesising the data of the individual trials.
To review the time to withdrawal, six- and 12-month remission, and first seizure of carbamazepine compared to phenytoin when used as monotherapy in people with partial onset seizures (simple partial, complex partial, or secondarily generalised tonic-clonic seizures) or generalised tonic-clonic seizures, with or without other generalised seizure types.
We searched the Cochrane Epilepsy Group's Specialised Register (16 September 2014), the Cochrane Central Register of Controlled Trials (CENTRAL; 2014, Issue 8), MEDLINE (1946 to 16 September 2014), SCOPUS (1823 to 16 September 2014), ClinicalTrials.gov (16 September 2014), and the World Health Organization (WHO) International Clinical Trials Registry Platform ICTRP (18 September 2014). We handsearched relevant journals, contacted pharmaceutical companies, original trial investigators and experts in the field.
Randomised controlled trials (RCTs) in children or adults with partial onset seizures or generalised onset tonic-clonic seizures with a comparison of carbamazepine monotherapy versus phenytoin monotherapy.
Data collection and analysis:
This was an individual participant data (IPD) review. Our primary outcome was time to withdrawal of allocated treatment, and our secondary outcomes were time to 12-month remission, time to six-month remission and time to first seizure post-randomisation. We used Cox proportional hazards regression models to obtain study-specific estimates of hazard ratios (HRs) with 95% confidence intervals (CIs) and the generic inverse variance method to obtain the overall pooled HR and 95% CI.
IPD were available for 595 participants out of 1192 eligible individuals, from four out of 12 trials (i.e. 50% of the potential data). For remission outcomes, HR > 1 indicates an advantage for phenytoin; and for first seizure and withdrawal outcomes, HR > 1 indicates an advantage for carbamazepine. Methodological quality of the four studies providing IPD was generally good and we rated it at low risk of bias overall in the analyses.The main overall results (pooled HR adjusted for seizure type) were time to withdrawal of allocated treatment: 1.04 (95% CI 0.78 to 1.39); time to 12-month remission: 1.01 (95% CI 0.78 to 1.31); time to six-month remission: 1.11 (95% CI 0.81 to 1.37); and time to first seizure: 0.85 (95% CI 0.70 to 1.04). The results suggest no overall statistically significant difference between the drugs for these outcomes. There is some evidence of an advantage for phenytoin for individuals with generalised onset seizures for our primary outcome (time to withdrawal of allocated treatment): pooled HR 0.42 (95% CI 0.18 to 0.96); and a statistical interaction between treatment effect and epilepsy type (partial versus generalised) for this outcome (P = 0.02), however misclassification of seizure type for up to 48 individuals (32% of those with generalised epilepsy) may have confounded the results of this review. Despite concerns over side effects leading to the withdrawal of phenytoin as first line treatment in the USA and Europe, we found no evidence that phenytoin is more likely to be associated with serious side effects than carbamazepine; 26 individuals withdrew from 290 randomised (9%) to carbamazepine due to adverse effects compared to 12 out of 299 (4%) randomised to phenytoin from four studies conducted in the USA and Europe (risk ratio (RR) 1.42, 95% CI 1.13 to 1.80, P = 0.014). We rated the quality of the evidence as low - moderate according to GRADE criteria, due to imprecision and potential misclassification of seizure type.
We have not found evidence that a statistically significant difference exists between carbamazepine and phenytoin for the efficacy outcomes examined in this review, however, CIs are wide and the possibility of important differences existing has not been excluded. There is no evidence in this review that phenytoin is more strongly associated with serious adverse events than carbamazepine. There is some evidence that participants with generalised seizures may be less likely to withdraw early from phenytoin than carbamazepine, but misclassification of seizure type may have impacted upon the results of this review. We recommend caution when interpreting the results of this review, and do not recommend that the results of this review alone should be used in choosing between carbamazepine and phenytoin. We recommend that future trials should be designed to the highest quality possible with considerations on allocation concealment and masking, choice of population, choice of outcomes and analysis, and presentation of results.
[Show abstract][Hide abstract] ABSTRACT: Pharmacogenetic studies have identified the presence of the HLA-A*31:01 allele as a predictor of cutaneous adverse drugs reactions (ADRs) to carbamazepine. This study aimed to ascertain the preferences of patients and clinicians to inform carbamazepine pharmacogenetic testing services.
Attributes of importance to people with epilepsy and neurologists were identified through interviews and from published sources. Discrete choice experiments (DCEs) were conducted in 82 people with epilepsy and 83 neurologists. Random-effects logit regression models were used to determine the importance of the attributes and direction of effect.
In the patient DCE, all attributes (seizure remission, reduction in seizure frequency, memory problems, skin rash and rare, severe ADRs) were significant. The estimated utility of testing was greater, at 0.52 (95% CI, 0.19 to 1.00) than not testing at 0.33 (95% CI, -0.07 to 0.81). In the physician DCE, cost, inclusion in the British National Formulary, coverage, negative predictive value (NPV), and positive predictive value (PPV) were significant. Marginal rates of substitution indicated that neurologists were willing to pay £5.87 for a 1 percentage point increase in NPV and £3.99 for a 1 percentage point increase in PPV.
The inclusion of both patients' and clinicians' perspectives represents an important contribution to the understanding of preferences towards pharmacogenetic testing prior to initiating carbamazepine. Both groups identified different attributes but had generally consistent preferences. Patients' acceptance of a decrease in treatment benefit for a reduced chance of severe ADRs adds support for the implementation of HLA-A*31:01 testing in routine practice.
This article is protected by copyright. All rights reserved.
British Journal of Clinical Pharmacology 07/2015; DOI:10.1111/bcp.12715 · 3.88 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Around half of people with epilepsy will not achieve seizure freedom on their first antiepileptic drug; many will require add-on treatment with another drug. Sometimes multiple treatment combinations are tried to achieve maximum seizure control, although around a third of people do not achieve complete seizure control. Lacosamide is an antiepileptic drug that has been licensed as an add-on treatment for partial epilepsy.
To evaluate the efficacy and tolerability of lacosamide when used as an add-on treatment for patients with drug-resistant partial epilepsy.
We searched the Cochrane Epilepsy Group's Specialized Register (21 May 2015), the Cochrane Central Register of Controlled Trials (CENTRAL , The Cochrane Library Issue 4, April 2015), MEDLINE (Ovid, 1946 to 21 May 2015), Scopus (1823 to 13 November 2014), ClinicalTrials.gov (21 May 2015) and the WHO International Clinical Trials Registry Platform (ICTRP, 21 May 2015). We imposed no language restrictions. We contacted UCB (sponsors of lacosamide) and experts in the field.
Randomised controlled trials of add-on lacosamide in people with drug-resistant partial epilepsy.
Two review authors independently assessed trials for inclusion and extracted the relevant data. We assessed the following outcomes: (1) 50% or greater reduction in seizure frequency; (2) seizure freedom; (3) treatment withdrawal for any reason; and (4) adverse events. Primary analyses were intention-to-treat. Summary risk ratios were estimated for each outcome.
We included three trials in our review (1311 participants), which were classified as having low risk of bias. All trials were placebo-controlled and assessed doses ranging from 200 mg to 600 mg per day. Trial duration ranged from 24 to 26 weeks. All trials used adequate methods of randomisation and were double-blind. Overall the quality of the evidence was rated as moderate to high. The overall risk ratio for a 50% or greater reduction in seizure frequency for all doses of lacosamide compared with placebo was 1.70 (95% confidence interval (CI) 1.38 to 2.10); for seizure freedom for all doses of lacosamide compared with placebo was 2.50 (95% CI 0.85 to 7.34); and for treatment withdrawal for all doses of lacosamide compared with placebo was 1.88 (95% CI 1.40 to 2.52). Adverse effects significantly associated with lacosamide were abnormal co-ordination (risk ratio (RR) 6.12, 99% CI 1.35 to 27.77), diplopia (RR 5.29, 99% CI 1.97 to 14.23), dizziness (RR 3.53, 99% CI 2.20 to 5.68), nausea (RR 2.37, 99% CI 1.23 to 4.58) and vomiting (RR 3.49, 99% CI 1.43 to 8.54). Adverse effects that were not statistically significant were headache (RR 1.34, 99% CI 0.83 to 2.18), fatigue (RR 2.11, 99% CI 0.92 to 4.85), nystagmus (RR 1.47, 99% CI 0.61 to 3.52) and somnolence (RR 1.44, 99% CI 0.67 to 3.09).
This review has shown lacosamide to be effective and fairly well tolerated in the short term when used as add-on treatment for drug-resistant partial epilepsy in adults. Higher doses of lacosamide may be more associated with adverse effects and withdrawal of the drug than lower doses. Additional evidence on children is needed, and longer-term efficacy is unknown.
[Show abstract][Hide abstract] ABSTRACT: This document provides guidance on the use of valproate in women and girls from a joint task force of the Commission of European Affairs of the International League Against Epilepsy (CEA-ILAE) and the European Academy of Neurology (EAN), following strengthened warnings from the Coordination Group for Mutual Recognition and Decentralised Procedures-Human (CMDh) of the European Medicines Agency (EMA), which highlight the risk of malformations and developmental problems in babies who are exposed to valproate in the womb. To produce these recommendations, the Task Force has considered teratogenic risks associated with use valproate and treatment alternatives, the importance of seizure control and of patient and foetal risks with seizures, and the effectiveness of valproate and treatment alternatives in the treatment of different epilepsies. The Task Force's recommendations include the following: Where possible, valproate should be avoided in women of childbearing potential. The choice of treatment for women of childbearing potential should be based on a shared decision between clinician and patient, and where appropriate the patient's representatives. Discussions should include a careful risk benefit assessment of reasonable treatment options for the patient's seizure or epilepsy type. For seizure (or epilepsy) types where valproate is the most effective treatment, the risks and benefits of valproate and other treatment alternatives should be discussed. Valproate should not be prescribed as a first-line treatment for focal epilepsy. Valproate may be offered as a first line treatment for epilepsy syndromes where it is the most effective treatment, including idiopathic (genetic) generalized syndromes associated with tonic clonic seizures. Valproate may be offered as a first-line treatment in situations where pregnancy is highly unlikely (e.g. significant intellectual or physical disability). Women and girls taking valproate require regular follow-up for ongoing consideration of the most appropriate treatment regimen. This article is protected by copyright. All rights reserved.
This article is protected by copyright. All rights reserved.
[Show abstract][Hide abstract] ABSTRACT: Background:
Vagus nerve stimulation (VNS) is a neuromodulatory treatment that is used as an adjunctive therapy for treating people with medically refractory epilepsy. VNS consists of chronic intermittent electrical stimulation of the vagus nerve, delivered by a programmable pulse generator. The majority of people given a diagnosis of epilepsy have a good prognosis, and their seizures will be controlled by treatment with a single antiepileptic drug (AED), but up to 20%-30% of patients will develop drug-resistant epilepsy, often requiring treatment with combinations of AEDs. The aim of this systematic review was to overview the current evidence for the efficacy and tolerability of vagus nerve stimulation when used as an adjunctive treatment for people with drug-resistant partial epilepsy. This is an updated version of a Cochrane review published in Issue 7, 2010.
To determine:(1) The effects on seizures of VNS compared to controls e.g. high-level stimulation compared to low-level stimulation (presumed sub-therapeutic dose); and(2) The adverse effect profile of VNS compared to controls e.g. high-level stimulation compared to low-level stimulation.
We searched the Cochrane Epilepsy Group's Specialised Register (23 February 2015), the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 23 February 2015), MEDLINE (1946 to 23 February 2015), SCOPUS (1823 to 23 February 2015), ClinicalTrials.gov (23 February 2015) and ICTRP (23 February 2015). No language restrictions were imposed.
The following study designs were eligible for inclusion: randomised, double-blind, parallel or crossover studies, controlled trials of VNS as add-on treatment comparing high and low stimulation paradigms (including three different stimulation paradigms - duty cycle: rapid, mid and slow) and VNS stimulation versus no stimulation or a different intervention. Eligible participants were adults or children with drug-resistant partial seizures not eligible for surgery or who failed surgery.
Data collection and analysis:
Two review authors independently selected trials for inclusion and extracted data. The following outcomes were assessed: (a) 50% or greater reduction in total seizure frequency; (b) treatment withdrawal (any reason); (c) adverse effects; (d) quality of life; (e) cognition; (f) mood. Primary analyses were intention-to-treat. Sensitivity best and worst case analyses were also undertaken to account for missing outcome data. Pooled Risk Ratios (RR) with 95% confidence intervals (95% Cl) were estimated for the primary outcomes of seizure frequency and treatment withdrawal. For adverse effects, pooled RRs and 99% CI's were calculated.
Five trials recruited a total of 439 participants and between them compared different types of VNS stimulation therapy. Baseline phase ranged from 4 to 12 weeks and double-blind treatment phases from 12 to 20 weeks in the five trials. Overall, two studies were rated as having a low risk of bias and three had an unclear risk of bias due to lack of reported information around study design. Effective blinding of studies of VNS is difficult due to the frequency of stimulation-related side effects such as voice alteration; this may limit the validity of the observed treatment effects. Four trials compared high frequency stimulation to low frequency stimulation and were included in quantitative syntheses (meta-analyses).The overall risk ratio (95% CI) for 50% or greater reduction in seizure frequency across all studies was 1.73 (1.13 to 2.64) showing that high frequency VNS was over one and a half times more effective than low frequency VNS. For this outcome, we rated the evidence as being moderate in quality due to incomplete outcome data in one included study; however results did not vary substantially and remained statistically significant for both the best and worst case scenarios. The risk ratio (RR) for treatment withdrawal was 2.56 (0.51 to 12.71), however evidence for this outcome was rated as low quality due to imprecision of the result and incomplete outcome data in one included study. The RR of adverse effects were as follows: (a) voice alteration and hoarseness 2.17 (99% CI 1.49 to 3.17); (b) cough 1.09 (99% CI 0.74 to 1.62); (c) dyspnea 2.45 (99% CI 1.07 to 5.60); (d) pain 1.01 (99% CI 0.60 to 1.68); (e) paresthesia 0.78 (99% CI 0.39 to 1.53); (f) nausea 0.89 (99% CI 0.42 to 1.90); (g) headache 0.90 (99% CI 0.48 to 1.69); evidence of adverse effects was rated as moderate to low quality due to imprecision of the result and/or incomplete outcome data in one included study. No important heterogeneity between studies was found for any of the outcomes.
VNS for partial seizures appears to be an effective and well tolerated treatment in 439 included participants from five trials. Results of the overall efficacy analysis show that VNS stimulation using the high stimulation paradigm was significantly better than low stimulation in reducing frequency of seizures. Results for the outcome "withdrawal of allocated treatment" suggest that VNS is well tolerated as withdrawals were rare. No significant difference was found in withdrawal rates between the high and low stimulation groups, however limited information was available from the evidence included in this review so important differences between high and low stimulation cannot be excluded . Adverse effects associated with implantation and stimulation were primarily hoarseness, cough, dyspnea, pain, paresthesia, nausea and headache, with hoarseness and dyspnea more likely to occur on high stimulation than low stimulation. However, the evidence on these outcomes is limited and of moderate to low quality. Further high quality research is needed to fully evaluate the efficacy and tolerability of VNS for drug resistant partial seizures.
[Show abstract][Hide abstract] ABSTRACT: About 100 000 people present to hospitals each year in England with an epileptic seizure. How they are managed is unknown; thus, the National Audit of Seizure management in Hospitals (NASH) set out to assess prior care, management of the acute event and follow-up of these patients. This paper describes the data from the second audit conducted in 2013.
154 emergency departments (EDs) across the UK.
Data from 4544 attendances (median age of 45 years, 57% men) showed that 61% had a prior diagnosis of epilepsy, 12% other neurological problems and 22% were first seizure cases. Each ED identified 30 consecutive adult cases presenting due to a seizure.
Details were recorded of the patient's prior care, management at hospital and onward referral to neurological specialists onto an online database. Descriptive results are reported at national level.
Of those with epilepsy, 498 (18%) were on no antiepileptic drug therapy and 1330 (48%) were on monotherapy. Assessments were often incomplete and witness histories were sought in only 759 (75%) of first seizure patients, 58% were seen by a senior doctor and 57% were admitted. For first seizure patients, advice on further seizure management was given to 264 (27%) and only 55% were referred to a neurologist or epilepsy specialist. For each variable, there was wide variability among sites that was not explicable. For the sites who partook in both audits, there was a trend towards better care in 2013, but this was small and dwarfed by the intersite variability.
These results have parallels with the Sentinel Audit of Stroke performed a decade earlier. There is wide intersite variability in care covering the entire care pathway, and a need for better organised and accessible care for these patients.
Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.
BMJ Open 03/2015; 5(3):e007325. DOI:10.1136/bmjopen-2014-007325 · 2.27 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Objective
Carbamazepine causes severe cutaneous adverse drug reactions that may be predicted by the presence of the HLA-A*31:01 allele in northern European populations. There is uncertainty as to whether routine testing of patients with epilepsy is cost-effective. We conducted an economic evaluation of HLA-A*31:01 testing from the perspective of the National Health Service (NHS) in the United Kingdom.MethodsA short-term, decision analytic model was developed to estimate the outcomes and costs associated with a policy of routine testing (with lamotrigine prescribed for patients who test positive) versus the current standard of care, which is carbamazepine prescribed without testing. A Markov model was used to estimate total costs and quality-adjusted life-years (QALYs) over a lifetime to account for differences in drug effectiveness and the long-term consequences of adverse drug reactions.ResultsTesting reduced the expected rate of cutaneous adverse drug reactions from 780 to 700 per 10,000 patients. The incremental cost-effectiveness ratio for pharmacogenetic testing versus standard care was £12,808 per QALY gained. The probability of testing being cost-effective at a threshold of £20,000 per QALY was 0.80, but the results were sensitive to estimated remission rates for alternative antiepileptic drugs (AEDs).SignificanceRoutine testing for HLA-A*31:01 in order to reduce the incidence of cutaneous adverse drug reactions in patients being prescribed carbamazepine for epilepsy is likely to represent a cost-effective use of health care resources.
[Show abstract][Hide abstract] ABSTRACT: Abstract
Objective We aimed to review and synthesise evidence from randomised controlled trials and prospective non-randomised studies of antidepressants used for treating depression in patients with epilepsy. The primary objectives were to evaluate the efficacy and safety of antidepressants in treating depressive symptoms and the effect on seizure recurrence.
Method A search of the databases was carried. There were no language restrictions. RCTs and prospective non randomised cohort controlled and uncontrolled studies investigating children or adults with epilepsy treated with an antidepressant for depressive symptoms were included. Data were extracted on trial design factors, patient demographics, and outcomes for each study. The primary outcomes were changes in depression scores and change in seizure frequency. Secondary outcomes included the number of patients withdrawing from the study and reasons of withdrawal and also any adverse events. Binary outcomes were presented as risk ratios and 95% CI. Continuous outcomes were presented as the standardised mean differences and 95% CI. Risk of bias was assessed using a version of the extended Cochrane Collaboration's tool for assessing risk of bias in both RCTs and non randomised studies.
Results Eight studies, three RCTs and five prospective cohort studies including 471 patients with epilepsy treated with an antidepressant were included. The RCTs were all single centred studies comparing antidepressant versus active control, placebo or no treatment. The five non randomised prospective cohort studies reported on outcomes mainly in partial epilepsy treated for depression with a selective serotonin reputable inhibitor(SSRI). We were unable to perform any meta analysis for the proportion with a >50% improvement in depression scores because the studies reported on different treatment comparisons. For the mean depression in depression score we were able to perform a limited meta analysis of two prospective cohort studies of citalopram including a total of 88 patients. The effect estimate was 1.17 (CI 0.96–1.38) for the mean difference in depression scores. Seizure frequency data were not reported in any RCTs. The treatment group on three prospective studies didn't report any significant increase in seizure frequency. Patients given an antidepressant were more likely to withdraw due to adverse events than inefficacy.
Conclusion Current evidence suggests antidepressants of various classes are effective in treating depressive symptoms associated with epilepsy. However we have no high quality evidence of informing on the best choice of antidepressant drug or class of drug in treating depression in patients with epilepsy. This review provides low quality evidence that SSRIs are not associated with seizure exacerbation, but there are currently no data comparing antidepressant classes.
Journal of neurology, neurosurgery, and psychiatry 02/2015; 86:e2. DOI:10.1136/jnnp-2015-311750.44 · 6.81 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Objective
There are competing explanations for persistent postoperative seizures after temporal lobe surgery. One is that 1 or more particular subtypes of mesial temporal lobe epilepsy (mTLE) exist that are particularly resistant to surgery. We sought to identify a common brain structural and connectivity alteration in patients with persistent postoperative seizures using preoperative quantitative magnetic resonance imaging and diffusion tensor imaging (DTI).Methods
We performed a series of studies in 87 patients with mTLE (47 subsequently rendered seizure free, 40 who continued to experience postoperative seizures) and 80 healthy controls. We investigated the relationship between imaging variables and postoperative seizure outcome. All patients had unilateral temporal lobe seizure onset, had ipsilateral hippocampal sclerosis as the only brain lesion, and underwent amygdalohippocampectomy.ResultsQuantitative imaging factors found not to be significantly associated with persistent seizures were volumes of ipsilateral and contralateral mesial temporal lobe structures, generalized brain atrophy, and extent of resection. There were nonsignificant trends for larger amygdala and entorhinal resections to be associated with improved outcome. However, patients with persistent seizures had significant atrophy of bilateral dorsomedial and pulvinar thalamic regions, and significant alterations of DTI-derived thalamotemporal probabilistic paths bilaterally relative to those patients rendered seizure free and controls, even when corrected for extent of mesial temporal lobe resection.InterpretationPatients with bihemispheric alterations of thalamotemporal structural networks may represent a subtype of mTLE that is resistant to temporal lobe surgery. Increasingly sensitive multimodal imaging techniques should endeavor to transform these group-based findings to individualize prediction of patient outcomes. Ann Neurol 2015;77:760–774
Annals of Neurology 01/2015; 77(5). DOI:10.1002/ana.24376 · 9.98 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Epilepsy is defined as the occurrence of at least two unprovoked seizures. Psychosis is a psychiatric illness characterized by the presence of delusions, hallucinations and thought disorder. Epidemiological studies suggest a bidirectional relationship between the two conditions. The exact reason for this is unclear but may relate to similar pathophysiology, genetic predisposition or iatrogenic interplay between anti-epileptic drugs and anti-psychotic drugs used to treat the conditions.
In comparison to other psychotic disorders, psychosis in epilepsy can be classified according to the temporal relationship with seizures i.e. ictal, postictal and interictal psychosis. Each sub-classification has its own clinical features, the commonest of which is interictal psychosis which may resemble schizophrenia in its presentation.
The management of psychosis in epilepsy and conversely management of epilepsy in psychotic disorders (schizophrenia) can be a challenge for clinicians. There is a perceived risk of exacerbating seizures with some anti-psychotics. Similarly, some anti-epileptic drugs may have a greater propensity to cause psychosis. Current uncertainty on best management policy means that some patients may not be receiving appropriate care.
In this critical review we summarize the available evidence on; linked pathophysiology, clinical features and how to distinguish between primary psychotic disorders and epilepsy associated psychosis, current evidence on risk of psychosis with available AEDs and the evidence base on risk of seizures with anti-psychotic drugs. We also include illustrative cases to highlight key learning points.
[Show abstract][Hide abstract] ABSTRACT: The objectives are as follows:
To review the time to withdrawal, remission and first seizure of 10 antiepileptic drugs (carbamazepine, phenytoin, valproate, phenobarbitone, oxcarbazepine, lamotrigine, gabapentin, topiramate, levetiracetam, zonisamide) currently used as monotherapy in children and adults with partial onset seizures or generalised tonic-clonic seizures with or without other generalised seizure types.
Cohrane Database of Systematic Reviews 12/2014; DOI:10.1002/14651858.CD011412.
[Show abstract][Hide abstract] ABSTRACT: Background Depressive disorders are the most common psychiatric comorbidity in patients with epilepsy, affecting around one-third, with a significant negative impact on quality of life. There is concern that patients may not be receiving appropriate treatment for their depression because of uncertainty regarding which antidepressant or class works best and the perceived risk of exacerbating seizures. This review aims to address these issues and inform clinical practice and future research. Objectives We aimed to review and synthesise evidence from randomised controlled trials of antidepressants and prospective non-randomised studies of antidepressants used for treating depression in patients with epilepsy. The primary objectives were to evaluate the efficacy and safety of antidepressants in treating depressive symptoms and the effect on seizure recurrence. Search methods We conducted a search of the following databases: the Cochrane Epilepsy Group Specialised Register; the Cochrane Central Register of Controlled Trials (CENTRAL 2014, Issue 5), MEDLINE (Ovid), SCOPUS, PsycINFO, www.clinicaltrials.gov and conference proceedings, including studies published up to 31 May 2014. There were no language restrictions. Selection criteria We included randomised controlled trials (RCTs) and prospective non-randomised cohort controlled and uncontrolled studies investigating children or adults with epilepsy treated with an antidepressant for depressive symptoms. The intervention group consisted of patients receiving an antidepressant drug in addition to an existing antiepileptic drug regimen. The control group(s) consisted of patients receiving a placebo, comparative antidepressant, psychotherapy or no treatment in addition to an existing antiepileptic drug regimen. Data collection and analysis We extracted data on trial design factors, patient demographics and outcomes for each study. The primary outcomes were changes in depression scores (proportion with a greater than 50% improvement or mean difference) and change in seizure frequency (mean difference or proportion with a seizure recurrence or episode of status epilepticus, or both). Secondary outcomes included the number of patients withdrawing from the study and reasons for withdrawal, as well as any adverse events. Two authors undertook data extraction separately for each included study. We then cross-checked the data extraction. We assessed risk of bias using a version of the extended Cochrane Collaboration tool for assessing risk of bias in both randomised and non-randomised studies. We presented binary outcomes as risk ratios (RRs) with 95% confidence intervals (CIs). We presented continuous outcomes as standardised mean differences (SMDs) with 95% CIs, and mean differences (MDs) with 95% CIs. If possible we intended to use meta-regression techniques to investigate possible sources of heterogeneity however this was not possible due to lack of data. Main results We included in the review eight studies (three RCTs and five prospective cohort studies) including 471 patients with epilepsy treated with an antidepressant. The RCTs were all single-centre studies comparing an antidepressant versus active control, placebo or no treatment. The five non-randomised prospective cohort studies reported on outcomes mainly in patients with partial epilepsy treated for depression with a selective serotonin reuptake inhibitor (SSRI). We rated all the RCTs and one prospective cohort study as having unclear risk of bias. We rated the four other prospective cohort studies as having high risk of bias. We were unable to perform any meta-analysis for the proportionwith a greater than 50% improvement in depression scores because the studies reported on different treatment comparisons. The results are presented descriptively and show a varied responder rate of between 24% and 97%, depending on the antidepressant given. For the mean difference in depression score we were able to perform a limited meta-analysis of two prospective cohort studies of citalopram, including a total of 88 patients. This gave low quality evidence for the effect estimate of 1.17 (95% CI 0.96 to 1.38) in depression scores. Seizure frequency data were not reported in any RCTs and we were unable to perform any meta-analysis for prospective cohort studies due to the different treatment comparisons. The results are presented descriptively and show that treatment in three studies with a selective serotonin reuptake inhibitor did not significantly increase seizure frequency. Patients given an antidepressant were more likely to withdraw due to adverse events than inefficacy. Reported adverse events for SSRIs included nausea, dizziness, sedation, gastrointestinal disturbance and sexual dysfunction. Across three comparisons we rated the evidence as moderate quality due to the small sizes of the contributing studies and only one study each contributing to the comparisons. We rated the evidence for the final comparison as low quality as there was concern over the study methods in the two contributing studies. Authors' conclusions Existing evidence on the effectiveness of antidepressants in treating depressive symptoms associated with epilepsy is very limited. Only one small RCT demonstrated a statistically significant effect of venlafaxine on depressive symptoms. We have no high quality evidence to inform the choice of antidepressant drug or class of drug in treating depression in people with epilepsy. This review provides low quality evidence of safety in terms of seizure exacerbation with SSRIs, but there are no available comparative data on antidepressant classes and safety in relation to seizures. There are currently no comparative data on antidepressants and psychotherapy in treating depression in epilepsy, although psychotherapy could be considered in patients unwilling to take antidepressants or where there are unacceptable side effects. Further comparative clinical trials of antidepressants and psychotherapy in large cohorts of patients with epilepsy and depression are required to better inform treatment policy in the future.