Tags

Type your tag names separated by a space and hit enter

Tolerability of new antiepileptic drugs: a network meta-analysis.
Eur J Clin Pharmacol 2017; 73(7):811-817EJ

Abstract

OBJECTIVE

The objective of this study was to perform a comparative assessment of tolerability of all licensed new antiepileptic drugs (AEDs) through a network meta-analysis (NMA) including all placebo-controlled double-blind clinical trials (RCTs) in all conditions in which these drugs have been tested.

METHODS

NMA with a frequentist approach was used to compare proportions of patients withdrawing because of adverse events (AEs). Analyses were conducted for all therapeutic doses pooled and specifically for high therapeutic doses. Patients treated with non-therapeutic doses of each drug were excluded.

RESULTS

A total of 195 RCTs were included in the current analysis, comprising a total of 28,013 patients treated with AEDs and 17,908 patients treated with placebo. RCTs included in the analysis were 8 for brivaracetam; 5 for eslicarbazepine; 22 for gabapentin; 7 for lacosamide; 14 for levetiracetam; 14 for lamotrigine; 6 for oxcarbazepine; 9 for perampanel; 50 for pregabalin; 5 for tiagabine; 36 for topiramate; 7 for zonisamide; 4 for gabapentin-extended formulation (ER); 2 each for levetiracetam-ER, lamotrigine-ER, and topiramate-ER; and 1 each for oxcarbazepine-ER and pregabalin-ER. Brivaracetam, gabapentin, gabapentin-ER, and levetiracetam had a significantly lower withdrawal rate compared to several other AEDs, while eslicarbazepine, lacosamide, oxcarbazepine, and topiramate had a higher withdrawal rate. Perampanel, lamotrigine, pregabalin, tiagabine, and zonisamide showed an intermediate pattern of tolerability. Additional analysis has been conducted through selection of highly recommended doses for each drug. This analysis has roughly confirmed results of head to head comparisons of the all-dose analysis, with some exceptions. A further analysis has been conducted after exclusion of RCTs in which patients were allocated to the therapeutic dose of the experimental drug without titration, and it failed to show clinically important differences.

SIGNIFICANCE

Relevant differences in short-term tolerability of AEDs have been observed between AEDs. Brivaracetam, gabapentin, and levetiracetam show the best tolerability profile while other AEDs are at higher risk for intolerable adverse effects.

Authors+Show Affiliations

Department of Medicine, Unit of Neurology, Florence Health Authority, Florence, Italy.Department of Medicine, Unit of Neurology, Florence Health Authority, Florence, Italy. fabio.giovannelli@unifi.it. Department of Neuroscience, Psychology, Pharmacology and Child Health (NEUROFARBA), University of Florence, Florence, Italy. fabio.giovannelli@unifi.it.Section of Neurology, Pisa University Hospital, Pisa, Italy.Department of Internal Medicine and Therapeutics, Division of Clinical and Experimental Pharmacology, University of Pavia, Pavia, Italy.Department of Medical and Surgical Sciences, Magna Graecia University, Catanzaro, Italy.School of Clinical Science, Bristol Heart Institute, University of Bristol, Bristol, UK.

Pub Type(s)

Journal Article
Meta-Analysis
Review

Language

eng

PubMed ID

28378057

Citation

Zaccara, Gaetano, et al. "Tolerability of New Antiepileptic Drugs: a Network Meta-analysis." European Journal of Clinical Pharmacology, vol. 73, no. 7, 2017, pp. 811-817.
Zaccara G, Giovannelli F, Giorgi FS, et al. Tolerability of new antiepileptic drugs: a network meta-analysis. Eur J Clin Pharmacol. 2017;73(7):811-817.
Zaccara, G., Giovannelli, F., Giorgi, F. S., Franco, V., Gasparini, S., & Benedetto, U. (2017). Tolerability of new antiepileptic drugs: a network meta-analysis. European Journal of Clinical Pharmacology, 73(7), pp. 811-817. doi:10.1007/s00228-017-2245-z.
Zaccara G, et al. Tolerability of New Antiepileptic Drugs: a Network Meta-analysis. Eur J Clin Pharmacol. 2017;73(7):811-817. PubMed PMID: 28378057.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Tolerability of new antiepileptic drugs: a network meta-analysis. AU - Zaccara,Gaetano, AU - Giovannelli,Fabio, AU - Giorgi,Filippo Sean, AU - Franco,Valentina, AU - Gasparini,Sara, AU - Benedetto,Umberto, Y1 - 2017/04/04/ PY - 2017/01/10/received PY - 2017/03/28/accepted PY - 2017/4/6/pubmed PY - 2018/3/23/medline PY - 2017/4/6/entrez KW - Adverse effects KW - Brivaracetam KW - Eslicarbazepine KW - Lacosamide KW - Meta-analysis KW - Network meta-analysis KW - Perampanel KW - Tolerability of antiepileptic drugs SP - 811 EP - 817 JF - European journal of clinical pharmacology JO - Eur. J. Clin. Pharmacol. VL - 73 IS - 7 N2 - OBJECTIVE: The objective of this study was to perform a comparative assessment of tolerability of all licensed new antiepileptic drugs (AEDs) through a network meta-analysis (NMA) including all placebo-controlled double-blind clinical trials (RCTs) in all conditions in which these drugs have been tested. METHODS: NMA with a frequentist approach was used to compare proportions of patients withdrawing because of adverse events (AEs). Analyses were conducted for all therapeutic doses pooled and specifically for high therapeutic doses. Patients treated with non-therapeutic doses of each drug were excluded. RESULTS: A total of 195 RCTs were included in the current analysis, comprising a total of 28,013 patients treated with AEDs and 17,908 patients treated with placebo. RCTs included in the analysis were 8 for brivaracetam; 5 for eslicarbazepine; 22 for gabapentin; 7 for lacosamide; 14 for levetiracetam; 14 for lamotrigine; 6 for oxcarbazepine; 9 for perampanel; 50 for pregabalin; 5 for tiagabine; 36 for topiramate; 7 for zonisamide; 4 for gabapentin-extended formulation (ER); 2 each for levetiracetam-ER, lamotrigine-ER, and topiramate-ER; and 1 each for oxcarbazepine-ER and pregabalin-ER. Brivaracetam, gabapentin, gabapentin-ER, and levetiracetam had a significantly lower withdrawal rate compared to several other AEDs, while eslicarbazepine, lacosamide, oxcarbazepine, and topiramate had a higher withdrawal rate. Perampanel, lamotrigine, pregabalin, tiagabine, and zonisamide showed an intermediate pattern of tolerability. Additional analysis has been conducted through selection of highly recommended doses for each drug. This analysis has roughly confirmed results of head to head comparisons of the all-dose analysis, with some exceptions. A further analysis has been conducted after exclusion of RCTs in which patients were allocated to the therapeutic dose of the experimental drug without titration, and it failed to show clinically important differences. SIGNIFICANCE: Relevant differences in short-term tolerability of AEDs have been observed between AEDs. Brivaracetam, gabapentin, and levetiracetam show the best tolerability profile while other AEDs are at higher risk for intolerable adverse effects. SN - 1432-1041 UR - https://www.unboundmedicine.com/medline/citation/28378057/Tolerability_of_new_antiepileptic_drugs:_a_network_meta_analysis_ L2 - https://dx.doi.org/10.1007/s00228-017-2245-z DB - PRIME DP - Unbound Medicine ER -