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Lamotrigine add-on for drug-resistant partial epilepsy.
Cochrane Database Syst Rev 2016; (6):CD001909CD

Abstract

BACKGROUND

This is an updated version of the Cochrane review published in The Cochrane Library 2010, Issue 1.Epilepsy is a common neurological disorder, affecting almost 0.5% to 1% of the population. For nearly 30% of these people, their epilepsy is refractory to currently available drugs. Pharmacological treatment remains the first choice to control epilepsy. Lamotrigine is one of the newer antiepileptic drugs and is the topic of this review. Lamotrigine in combination with other antiepileptic drugs (add-on) can reduce seizures, but with some adverse effects. The aim of this systematic review was to overview the current evidence for the efficacy and tolerability of lamotrigine when used as an adjunctive treatment for people with refractory partial epilepsy.

OBJECTIVES

To determine the effects of lamotrigine on (1) seizures, (2) adverse effect profile, and (3) cognition and quality of life, compared to placebo controls, when used as an add-on treatment for people with refractory partial epilepsy.

SEARCH METHODS

For the previous version of the review, the authors searched the Cochrane Epilepsy Group Specialized Register (January 2010), the Cochrane Central Register of Controlled Trials (CENTRAL, The Cochrane Library 2010, Issue 1), MEDLINE (1950 to January 2010), and reference lists of articles.For this update, we searched the Cochrane Epilepsy Group Specialized Register (28 May 2015), CENTRAL (The Cochrane Library 2015, Issue 4), MEDLINE (Ovid, 1946 to May 2015), and reference lists of articles. We also contacted the manufacturers of lamotrigine (GlaxoSmithKline). No language restrictions were imposed.

SELECTION CRITERIA

Randomised placebo-controlled trials of people with drug-resistant partial epilepsy of any age, in which an adequate method of concealment of randomisation was used. The studies were double-, single- or unblinded. For cross-over studies, the first treatment period was treated as a parallel trial. Eligible participants were adults or children with drug-resistant partial epilepsy.

DATA COLLECTION AND ANALYSIS

For this update, two review authors independently assessed the trials for inclusion, and extracted data. Outcomes included 50% or greater reduction in seizure frequency, treatment withdrawal (any reason), adverse effects, effects on cognition and quality of life. Primary analyses were by intention-to-treat. Sensitivity best and worse case analyses were 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% Cls were calculated.

MAIN RESULTS

We did not identify any new studies for this update, therefore, the results are unchanged.For the previous version of the review, the authors found five parallel add-on studies and eight cross-over studies in adults or children with refractory focal epilepsy, and one parallel add-on study with a responder-enriched design in infants. In total, these 14 studies included 1958 participants (38 infants, 199 children, and 1721 adults). Baseline phases ranged from 4 to 12 weeks; treatment phases from 8 to 36 weeks. Overall, eleven studies (n = 1243 participants) were rated as having a low risk of bias, and three (n = 715 participants) had un unclear risk of bias due to lack of reported information around study design. Effective blinding of studies was reported in three studies (n = 504 participants). The overall risk ratio (RR) for 50% or greater reduction in seizure frequency was 1.80 (95% CI 1.45 to 2.23; 12 RCTs) for twelve studies (n = 1322 participants, adults and children) indicating that lamotrigine was significantly more effective than placebo in reducing seizure frequency. The overall RR for treatment withdrawal (for any reason) was 1.11 (95% CI 0.90 to 1.36; 14 RCTs) for fourteen studies (n = 1958 participants). The adverse events significantly associated with lamotrigine were: ataxia, dizziness, diplopia, and nausea. The RR of these adverse effects were as follows: ataxia 3.34 (99% Cl 2.01 to 5.55; 12 RCTs; n = 1524); dizziness 2.00 (99% Cl 1.51 to 2.64;13 RCTs; n = 1767); diplopia 3.79 (99% Cl 2.15 to 6.68; 3 RCTs; n = 943); nausea 1.81 (99% Cl 1.22 to 2.68; 12 RCTs; n = 1486). The limited data available precluded any conclusions about effects on cognition and quality of life. No important heterogeneity between studies was found for any of the outcomes. Overall, we assessed the evidence as high to moderate quality, due to incomplete data for some outcomes.

AUTHORS' CONCLUSIONS

Lamotrigine as an add-on treatment for partial seizures appears to be effective in reducing seizure frequency, and seems to be fairly well tolerated. However, the trials were of relatively short duration and provided no evidence for the long-term. Further trials are needed to assess the long-term effects of lamotrigine, and to compare it with other add-on drugs.Since we did not find any new studies, our conclusions remain unchanged.

Authors+Show Affiliations

Department of Neurology, The Nerve Centre, 5/1 Rajachar Street, T Nagar, Chennai, Tamil Nadu, India, 600017.No affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Meta-Analysis
Research Support, Non-U.S. Gov't
Review
Systematic Review

Language

eng

PubMed ID

27329345

Citation

Ramaratnam, Sridharan, et al. "Lamotrigine Add-on for Drug-resistant Partial Epilepsy." The Cochrane Database of Systematic Reviews, 2016, p. CD001909.
Ramaratnam S, Panebianco M, Marson AG. Lamotrigine add-on for drug-resistant partial epilepsy. Cochrane Database Syst Rev. 2016.
Ramaratnam, S., Panebianco, M., & Marson, A. G. (2016). Lamotrigine add-on for drug-resistant partial epilepsy. The Cochrane Database of Systematic Reviews, (6), p. CD001909. doi:10.1002/14651858.CD001909.pub2.
Ramaratnam S, Panebianco M, Marson AG. Lamotrigine Add-on for Drug-resistant Partial Epilepsy. Cochrane Database Syst Rev. 2016 Jun 22;(6)CD001909. PubMed PMID: 27329345.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Lamotrigine add-on for drug-resistant partial epilepsy. AU - Ramaratnam,Sridharan, AU - Panebianco,Mariangela, AU - Marson,Anthony G, Y1 - 2016/06/22/ PY - 2016/6/23/entrez PY - 2016/6/23/pubmed PY - 2016/8/18/medline SP - CD001909 EP - CD001909 JF - The Cochrane database of systematic reviews JO - Cochrane Database Syst Rev IS - 6 N2 - BACKGROUND: This is an updated version of the Cochrane review published in The Cochrane Library 2010, Issue 1.Epilepsy is a common neurological disorder, affecting almost 0.5% to 1% of the population. For nearly 30% of these people, their epilepsy is refractory to currently available drugs. Pharmacological treatment remains the first choice to control epilepsy. Lamotrigine is one of the newer antiepileptic drugs and is the topic of this review. Lamotrigine in combination with other antiepileptic drugs (add-on) can reduce seizures, but with some adverse effects. The aim of this systematic review was to overview the current evidence for the efficacy and tolerability of lamotrigine when used as an adjunctive treatment for people with refractory partial epilepsy. OBJECTIVES: To determine the effects of lamotrigine on (1) seizures, (2) adverse effect profile, and (3) cognition and quality of life, compared to placebo controls, when used as an add-on treatment for people with refractory partial epilepsy. SEARCH METHODS: For the previous version of the review, the authors searched the Cochrane Epilepsy Group Specialized Register (January 2010), the Cochrane Central Register of Controlled Trials (CENTRAL, The Cochrane Library 2010, Issue 1), MEDLINE (1950 to January 2010), and reference lists of articles.For this update, we searched the Cochrane Epilepsy Group Specialized Register (28 May 2015), CENTRAL (The Cochrane Library 2015, Issue 4), MEDLINE (Ovid, 1946 to May 2015), and reference lists of articles. We also contacted the manufacturers of lamotrigine (GlaxoSmithKline). No language restrictions were imposed. SELECTION CRITERIA: Randomised placebo-controlled trials of people with drug-resistant partial epilepsy of any age, in which an adequate method of concealment of randomisation was used. The studies were double-, single- or unblinded. For cross-over studies, the first treatment period was treated as a parallel trial. Eligible participants were adults or children with drug-resistant partial epilepsy. DATA COLLECTION AND ANALYSIS: For this update, two review authors independently assessed the trials for inclusion, and extracted data. Outcomes included 50% or greater reduction in seizure frequency, treatment withdrawal (any reason), adverse effects, effects on cognition and quality of life. Primary analyses were by intention-to-treat. Sensitivity best and worse case analyses were 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% Cls were calculated. MAIN RESULTS: We did not identify any new studies for this update, therefore, the results are unchanged.For the previous version of the review, the authors found five parallel add-on studies and eight cross-over studies in adults or children with refractory focal epilepsy, and one parallel add-on study with a responder-enriched design in infants. In total, these 14 studies included 1958 participants (38 infants, 199 children, and 1721 adults). Baseline phases ranged from 4 to 12 weeks; treatment phases from 8 to 36 weeks. Overall, eleven studies (n = 1243 participants) were rated as having a low risk of bias, and three (n = 715 participants) had un unclear risk of bias due to lack of reported information around study design. Effective blinding of studies was reported in three studies (n = 504 participants). The overall risk ratio (RR) for 50% or greater reduction in seizure frequency was 1.80 (95% CI 1.45 to 2.23; 12 RCTs) for twelve studies (n = 1322 participants, adults and children) indicating that lamotrigine was significantly more effective than placebo in reducing seizure frequency. The overall RR for treatment withdrawal (for any reason) was 1.11 (95% CI 0.90 to 1.36; 14 RCTs) for fourteen studies (n = 1958 participants). The adverse events significantly associated with lamotrigine were: ataxia, dizziness, diplopia, and nausea. The RR of these adverse effects were as follows: ataxia 3.34 (99% Cl 2.01 to 5.55; 12 RCTs; n = 1524); dizziness 2.00 (99% Cl 1.51 to 2.64;13 RCTs; n = 1767); diplopia 3.79 (99% Cl 2.15 to 6.68; 3 RCTs; n = 943); nausea 1.81 (99% Cl 1.22 to 2.68; 12 RCTs; n = 1486). The limited data available precluded any conclusions about effects on cognition and quality of life. No important heterogeneity between studies was found for any of the outcomes. Overall, we assessed the evidence as high to moderate quality, due to incomplete data for some outcomes. AUTHORS' CONCLUSIONS: Lamotrigine as an add-on treatment for partial seizures appears to be effective in reducing seizure frequency, and seems to be fairly well tolerated. However, the trials were of relatively short duration and provided no evidence for the long-term. Further trials are needed to assess the long-term effects of lamotrigine, and to compare it with other add-on drugs.Since we did not find any new studies, our conclusions remain unchanged. SN - 1469-493X UR - https://www.unboundmedicine.com/medline/citation/27329345/Lamotrigine_add_on_for_drug_resistant_partial_epilepsy_ L2 - https://doi.org/10.1002/14651858.CD001909.pub2 DB - PRIME DP - Unbound Medicine ER -