Tags

Type your tag names separated by a space and hit enter

Zonisamide add-on for drug-resistant partial epilepsy.

Abstract

BACKGROUND

The majority of people with epilepsy have a good prognosis and their seizures can be well controlled with the use of a single antiepileptic agent, but up to 30% develop refractory epilepsy, especially those with partial seizures. In this review we summarise the current evidence regarding zonisamide, when used as an add-on treatment for drug-resistant partial epilepsy.

OBJECTIVES

To evaluate the efficacy and tolerability of zonisamide when used as an add-on treatment for people with drug-resistant partial epilepsy.

SEARCH METHODS

We searched the Cochrane Epilepsy Group Specialized Register (12 February 2013), the Cochrane Central Register of Controlled Trials (The Cochrane Library 2013, Issue 1) (January 2013), MEDLINE (Ovid, 1946 to 12 February 2013), SCOPUS (13 February 2013), ClinicalTrials.gov (12 February 2013) and the WHO International Clinical Trials Registry Platform ICTRP (13 February 2013). In addition, we contacted Eisai Limited (makers and licensees of zonisamide) and experts in the field to seek any ongoing/unpublished studies.

SELECTION CRITERIA

Randomised, placebo-controlled, add-on trials of zonisamide in people with drug-resistant partial epilepsy.

DATA COLLECTION AND ANALYSIS

Two review authors independently selected trials for inclusion and extracted data. Outcomes were: (1) 50% or greater reduction in total seizure frequency; (2) treatment withdrawal; (3) adverse effects. Primary analyses were intention-to-treat. We estimated summary risk ratios (RRs) for each outcome. All studies were assessed for risk of bias using the Cochrane risk of bias tool and the quality of evidence was assessed using the GRADE approach and presented in a summary of findings table.

MAIN RESULTS

Five trials (949 participants) were included. The overall RR with 95% confidence interval (CI) for 50% reduction in seizure frequency compared to placebo for 300 to 500 mg/day of zonisamide was 2.00 (95% CI 1.58 to 2.54). The RR for 50% reduction in seizure frequency compared to placebo for any dose of zonisamide (100 to 500 mg per day) was 1.92 (95% CI 1.52 to 2.42). The number needed to treat (NNT) was 6 for this outcome. Two trials provide evidence of a dose response relationship for this outcome. The RR for treatment withdrawal for 300 to 500 mg/day of zonisamide compared to placebo was 1.64 (95% CI 1.20 to 2.25) and for 100 to 500 mg per day was 1.47 (95% CI 1.07 to 2.01). NNT for this outcome was 21. The CIs of the following adverse effects indicate that they are significantly associated with zonisamide: ataxia 3.77 (99% CI 1.28 to 11.11); somnolence 1.83 (99% CI 1.08 to 3.11); agitation 2.35 (99% CI 1.05 to 5.27) and anorexia 2.71 (99% CI 1.29 to 5.69). Across the 5 studies, risk of bias domains were rated as low is bias or unclear. None of the evidence for outcomes was downgraded for quality.

AUTHORS' CONCLUSIONS

Zonisamide has efficacy as an add-on treatment in people with drug-resistant partial epilepsy. In this review minimum effective and maximum tolerated doses cannot be identified. The trials reviewed were of a maximum stable-dose phase of 18 weeks in duration and results cannot be used to confirm longer periods of effectiveness in seizure control. The results cannot be extrapolated to monotherapy or to people with other seizure types or epilepsy syndromes.

Authors+Show Affiliations

Department of Molecular and Clinical Pharmacology, Institute of Translational Medicine, University of Liverpool, Clinical Sciences Centre for Research and Education, Lower Lane, Fazakerley, Liverpool, UK, L9 7LJ.No affiliation info availableNo affiliation info availableNo 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

24353187

Citation

Carmichael, Katie, et al. "Zonisamide Add-on for Drug-resistant Partial Epilepsy." The Cochrane Database of Systematic Reviews, 2013, p. CD001416.
Carmichael K, Pulman J, Lakhan SE, et al. Zonisamide add-on for drug-resistant partial epilepsy. Cochrane Database Syst Rev. 2013.
Carmichael, K., Pulman, J., Lakhan, S. E., Parikh, P., & Marson, A. G. (2013). Zonisamide add-on for drug-resistant partial epilepsy. The Cochrane Database of Systematic Reviews, (12), CD001416. https://doi.org/10.1002/14651858.CD001416.pub3
Carmichael K, et al. Zonisamide Add-on for Drug-resistant Partial Epilepsy. Cochrane Database Syst Rev. 2013 Dec 19;(12)CD001416. PubMed PMID: 24353187.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Zonisamide add-on for drug-resistant partial epilepsy. AU - Carmichael,Katie, AU - Pulman,Jennifer, AU - Lakhan,Shaheen Emmanuel, AU - Parikh,Prachi, AU - Marson,Anthony G, Y1 - 2013/12/19/ PY - 2013/12/20/entrez PY - 2013/12/20/pubmed PY - 2014/4/3/medline SP - CD001416 EP - CD001416 JF - The Cochrane database of systematic reviews JO - Cochrane Database Syst Rev IS - 12 N2 - BACKGROUND: The majority of people with epilepsy have a good prognosis and their seizures can be well controlled with the use of a single antiepileptic agent, but up to 30% develop refractory epilepsy, especially those with partial seizures. In this review we summarise the current evidence regarding zonisamide, when used as an add-on treatment for drug-resistant partial epilepsy. OBJECTIVES: To evaluate the efficacy and tolerability of zonisamide when used as an add-on treatment for people with drug-resistant partial epilepsy. SEARCH METHODS: We searched the Cochrane Epilepsy Group Specialized Register (12 February 2013), the Cochrane Central Register of Controlled Trials (The Cochrane Library 2013, Issue 1) (January 2013), MEDLINE (Ovid, 1946 to 12 February 2013), SCOPUS (13 February 2013), ClinicalTrials.gov (12 February 2013) and the WHO International Clinical Trials Registry Platform ICTRP (13 February 2013). In addition, we contacted Eisai Limited (makers and licensees of zonisamide) and experts in the field to seek any ongoing/unpublished studies. SELECTION CRITERIA: Randomised, placebo-controlled, add-on trials of zonisamide in people with drug-resistant partial epilepsy. DATA COLLECTION AND ANALYSIS: Two review authors independently selected trials for inclusion and extracted data. Outcomes were: (1) 50% or greater reduction in total seizure frequency; (2) treatment withdrawal; (3) adverse effects. Primary analyses were intention-to-treat. We estimated summary risk ratios (RRs) for each outcome. All studies were assessed for risk of bias using the Cochrane risk of bias tool and the quality of evidence was assessed using the GRADE approach and presented in a summary of findings table. MAIN RESULTS: Five trials (949 participants) were included. The overall RR with 95% confidence interval (CI) for 50% reduction in seizure frequency compared to placebo for 300 to 500 mg/day of zonisamide was 2.00 (95% CI 1.58 to 2.54). The RR for 50% reduction in seizure frequency compared to placebo for any dose of zonisamide (100 to 500 mg per day) was 1.92 (95% CI 1.52 to 2.42). The number needed to treat (NNT) was 6 for this outcome. Two trials provide evidence of a dose response relationship for this outcome. The RR for treatment withdrawal for 300 to 500 mg/day of zonisamide compared to placebo was 1.64 (95% CI 1.20 to 2.25) and for 100 to 500 mg per day was 1.47 (95% CI 1.07 to 2.01). NNT for this outcome was 21. The CIs of the following adverse effects indicate that they are significantly associated with zonisamide: ataxia 3.77 (99% CI 1.28 to 11.11); somnolence 1.83 (99% CI 1.08 to 3.11); agitation 2.35 (99% CI 1.05 to 5.27) and anorexia 2.71 (99% CI 1.29 to 5.69). Across the 5 studies, risk of bias domains were rated as low is bias or unclear. None of the evidence for outcomes was downgraded for quality. AUTHORS' CONCLUSIONS: Zonisamide has efficacy as an add-on treatment in people with drug-resistant partial epilepsy. In this review minimum effective and maximum tolerated doses cannot be identified. The trials reviewed were of a maximum stable-dose phase of 18 weeks in duration and results cannot be used to confirm longer periods of effectiveness in seizure control. The results cannot be extrapolated to monotherapy or to people with other seizure types or epilepsy syndromes. SN - 1469-493X UR - https://www.unboundmedicine.com/medline/citation/24353187/Zonisamide_add_on_for_drug_resistant_partial_epilepsy_ DB - PRIME DP - Unbound Medicine ER -