Gabapentin monotherapy for epilepsy: A review

Article type: Review Article

Authors: Ziganshina, Liliya Eugenevna^{a; b; c;} | Abakumova, Tatyana^d | Hoyle, Charles H.V.^{e; †}

Affiliations: [a] Centre for Knowledge Translation, Federal State Budgetary Educational Institution of Continuing Professional Education “Russian Medical Academy of Continuing Professional Education”, The Ministry of Health of the Russian Federation (RMANPO), Moscow, Russian Federation | [b] Department of Pharmacology, Kazan State Medical University (KSMU), The Ministry of Health of the Russian Federation, Kazan, Russian Federation | [c] Department of General and Clinical Pharmacology, Peoples’ Friendship University of Russia named after Patrice Lumumba (RUDN), Moscow, Russian Federation | [d] Department of Biochemistry, Biotechnology and Pharmacology, Kazan (Volga region) Federal University, Kazan, Russian Federation | [e] Kazan Medical Journal, Kazan, Russian Federation

Correspondence: [*] Address for correspondence: Liliya Eugenevna Ziganshina. E-mail: [email protected]

Note: [†] Charles H.V. Hoyle passed away on 23 November 2021.

Abstract: BACKGROUND:Epilepsy is one of the most common chronic neurological disorders, affecting more than 50 million people globally. In this review we summarised the evidence from randomised controlled trials of gabapentin used as monotherapy for the treatment of focal epilepsy, both newly diagnosed and drug-resistant, with or without secondary generalisation. OBJECTIVE:To assess the effects of gabapentin monotherapy for people with epileptic focal seizures with and without secondary generalisation. METHODS:We searched the Cochrane Register of Studies (CRS Web) and MEDLINE (Ovid, 1946 to 24 February 2020) on 25 February 2020. CRS Web includes randomised or quasi-randomised controlled trials from PubMed, Embase, ClinicalTrials.gov, the World Health Organization International Clinical Trials Registry Platform, the Cochrane Central Register of Controlled Trials (CENTRA), and the specialised registers of Cochrane Review Groups including the Cochrane Epilepsy Group. We also searched several Russian databases, reference lists of relevant studies, ongoing trials registers, conference proceedings, and we contacted trial authors. RESULTS:We found five randomised controlled trials (3167 participants) comparing gabapentin to other antiepileptic drugs (AEDs) and differing doses of gabapentin as monotherapy for newly diagnosed focal epilepsy and drug- resistant focal epilepsy with or without secondary generalisation. Two review authors independently applied the inclusion criteria, assessed trial quality, risk of bias, and extracted data. We used the GRADE approach to assess the certainty of evidence and present seven patient-important outcomes in the “Summary of findings” tables. The quality of evidence was very low to moderate due to poor reporting quality, poor trial design, and other risks of bias, such as selective presentation of findings and potential heavy industry input. Better quality research may change our certainty in the effect estimates. None of the included trials reported on the number of people with 50% or greater reduction in seizures and time to withdrawal (retention time) in an extractable way. Gabapentin-treated participants were more likely to withdraw from treatment for any cause (285/539) than those treated with lamotrigine, oxcarbazepine, or topiramate pooled together (695/1317) (RR 1.13, 95% CI 1.02 to 1.25; 3 studies, 1856 participants; moderate-certainty evidence), but not carbamazepine. Fewer people treated with gabapentin withdrew from treatment owing to adverse events (190/525) than those treated with carbamazepine, oxcarbazepine, or topiramate (479/1238), (RR 0.79, 95% CI 0.69 to 0.91; 1763 participants, 3 studies; moderate-certainty evidence), but not lamotrigine. CONCLUSION:Gabapentin as monotherapy probably controlled seizures no better and no worse than comparator AEDs (lamotrigine, carbamazepine, oxcarbazepine, and topiramate). Compared to carbamazepine, gabapentin was probably better in retaining people in studies and preventing withdrawals due to adverse events. The most common side effects associated with gabapentin were ataxia (poor co-ordination and unsteady gait), dizziness, fatigue, and drowsiness.

Keywords: Gabapentin, epilepsy, monotherapy, lamotrigine, carbamazepine, oxcarbazepine, topiramate

DOI: 10.3233/JRS-235001

Journal: International Journal of Risk & Safety in Medicine, vol. 34, no. 3, pp. 243-286, 2023