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<DOC> |
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<TITLE TRANSLATED="NO">Topiramate add-on for drug-resistant partial epilepsy</TITLE> |
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<SUMMARY TRANSLATED="NO"> |
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<SUMMARY_TITLE>Topiramate add-on for drug-resistant partial epilepsy</SUMMARY_TITLE> |
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<SUMMARY_BODY> |
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<P>Topiramate is effective as an add-on treatment for drug-resistant partial epilepsy.</P> |
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<P>Epilepsy is a disorder where recurrent seizures are caused by abnormal electrical discharges from the brain. Most seizures can be controlled by a single antiepileptic drug. Unfortunately some people require more than one antiepileptic medication to control their seizures, especially if these originate from one area of the brain (partial epilepsy), instead of being generalised.</P> |
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<P>We carried out a search of databases on 18 June 2013. Eleven trials were found which included 1401 people with partial epilepsy. These trials were all randomised controlled trials which compared the antiepileptic drug topiramate to a placebo drug for a period of up to 18 weeks. Taking all the evidence of the trials into account, the review found that topiramate is three times more effective when used with other drugs than placebo to reduce the number of seizures in drug-resistant partial epilepsy. However, adding topiramate to the usual treatment is associated with an increase in side effects such as problems with co-ordination (ataxia), concentration, dizziness, drowsiness (somnolence), fatigue, nausea, 'thinking abnormally', tickling or numbness of the skin (paraesthesia) and weight loss.</P> |
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<P>We assessed the trials with regards to bias and quality. Overall, we rated the quality of the evidence as moderate. The trials included in this review did not examine the long-term effects of topiramate as an add-on treatment and future research should consider examining dose.</P> |
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</SUMMARY_BODY> |
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</SUMMARY> |
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<ABSTRACT TRANSLATED="NO"> |
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<ABS_BACKGROUND> |
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<P>The majority of people with epilepsy have a good prognosis and their seizures are controlled by a single antiepileptic drug. However, up to 20% of patients from population-based studies and up to 30% from clinical series (not population-based) develop drug-resistant epilepsy, especially those with partial onset seizures. In this review we summarise the current evidence regarding topiramate, an antiepileptic drug first marketed in 1996, when used as an add-on treatment for drug-resistant partial epilepsy. This is an updated version of the original Cochrane review published in Issue 3, 1999.</P> |
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</ABS_BACKGROUND> |
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<ABS_OBJECTIVES> |
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<P>To evaluate the efficacy and safety of topiramate when used as an add-on treatment for people with drug-resistant partial epilepsy.</P> |
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</ABS_OBJECTIVES> |
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<ABS_SEARCH_STRATEGY> |
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<P>We searched the Cochrane Epilepsy Group Specialised Register (June 2013); the Cochrane Central Register of Controlled Trials (CENTRAL) (<I>The Cochrane Library </I>2013,<I> </I>Issue 5); MEDLINE (1946 to 2013); SCOPUS (1823 to 2013); ClinicalTrials.gov and ICTRP. We imposed no language restrictions. We also contacted the manufacturers of topiramate and researchers in the field to identify any ongoing or unpublished studies.</P> |
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</ABS_SEARCH_STRATEGY> |
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<ABS_SELECTION_CRITERIA> |
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<P>Randomised, placebo-controlled or active drug controlled add-on trials of topiramate, recruiting people with drug-resistant partial epilepsy.</P> |
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</ABS_SELECTION_CRITERIA> |
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<ABS_DATA_COLLECTION> |
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<P>Two review authors independently selected trials for inclusion and extracted the relevant data. We assessed the following outcomes: (a) 50% or greater reduction in seizure frequency; (b) seizure freedom; (c) treatment withdrawal (any reason); (d) side effects. Primary analyses were intention-to-treat and summary risk ratios (RR) with 95% confidence intervals (95% CI) are presented. We evaluated dose response in regression models. We carried out a 'Risk of bias' assessment for each included study using the Cochrane 'Risk of bias' tool and assessed the overall quality of evidence using the GRADE approach, which we presented in a 'Summary of findings' table.</P> |
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</ABS_DATA_COLLECTION> |
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<ABS_RESULTS> |
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<P>Eleven trials were included, representing 1401 randomised participants. Baseline phases ranged from 4 to 12 weeks and double-blind phases from 11 to 19 weeks. The RR for a 50% or greater reduction in seizure frequency compared to placebo was 2.97 (95% CI 2.38 to 3.72). Dose regression analysis shows increasing effect with increasing dose, but found no advantage for doses over 300 or 400 mg per day. The RR for seizure freedom (95% CI) compared to placebo was 3.41 (95% CI 1.37 to 8.51). The RR for treatment withdrawal compared to placebo was 2.44 (95% CI 1.64 to 3.62). The RRs for the following side effects indicate that they are significantly associated with topiramate: ataxia 2.29 (99% CI 1.10 to 4.77); concentration difficulties 7.81 (2.08 to 29.29); dizziness 1.54 (99% CI 1.07 to 2.22); fatigue 2.19 (99% CI 1.42 to 3.40); paraesthesia 3.91 (1.51 to 10.12); somnolence 2.29 (99% CI 1.49 to 3.51); 'thinking abnormally' 5.70 (99% CI 2.26 to 14.38) and weight loss 3.47 (1.55 to 7.79). Evidence of publication bias was found (P-value from the Egger test was P=0.003). We rated all studies included in the review as having either low or unclear risk of bias. Overall, we assessed the evidence as moderate quality due to the evidence of publication bias.</P> |
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</ABS_RESULTS> |
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<ABS_CONCLUSIONS> |
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<P>Topiramate has efficacy as an add-on treatment for drug-resistant partial epilepsy in that it is three times more effective compared to a placebo in reducing seizures. However, the trials reviewed were of relatively short duration and provide no evidence for the long-term efficacy of topiramate. In the short term topiramate as an add-on has been shown to be associated with several adverse events. The results of this review cannot be extrapolated to monotherapy or treatment of other epilepsy types and future research should consider examining the effect of dose. </P> |
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</ABS_CONCLUSIONS> |
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</ABSTRACT> |
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</DOC> |
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