Safety and efficacy of vigabatrin and carbamazepine in newly diagnosed epilepsy: A multicentre randomised double-blind study

David Chadwick, J. Baldy-Moulinier, E. Ben-Manachem, R. Beran, A. Bes, L. D. Biermann, J. M. Bird, L. Boon, E. Byrne, E. P. Calandre, E. V. de Seijas, J. A. Tejerina, R. Canger, A. Saltarelli, N. E F Cartlidge, R. N. Corston, V. Cosi, C. Dellaportas, J. Duncan, W. Van PaesschenM. Dam, G. Danta, H. Gadot, A. N. Gale, D. Gisselbrecht, M. Gross, W. M. Guldenpfennig, J. Haan, S. J L Howell, G. S. Venables, J. Jankovic, R. Kälviäinen, P. Riekkinen, K. Kennedy, G. Kramer, P. H. Kritzinger, J. Manelis, R. Michelucci, C. A. Tassinari, M. Neufeld, B. Pederson, F. Pisani, A. Reches, B. Ried, E. A C M Saunders, E. Somerville, L. Spechio, L. A. Neve, L. Tramacere, H. Stefan, A. Tartara, A. D. Van As, C. A. Van Donsellar, M. Weber, H. G. Wieser, G. Zaccara, G. T. Gomez

Research output: Contribution to journalArticle

Abstract

Background. Vigabatrin is a newly licensed drug for use in patients with epilepsy. We investigated whether this drug was comparable to standard first-line monotherapy in efficacy and incidence of adverse events. Methods. We enrolled 459 patients with newly diagnosed, untreated partial epileptic seizures from 44 centres and randomly assigned them carbamazepine 600 mg daily (n = 230) or vigabatrin 2 g daily (n = 229). After initial maintenance doses were reached, doses were adjusted downwards (in the case of adverse events) or upwards (in the case of seizures) by the clinician. The primary outcome was time to withdrawal because of lack of efficacy or adverse events. Secondary outcomes included efficacy (time to 6-month remission of seizures, time to first seizure after initial dose stabilisation), and adverse events (incidence and severity). Analysis was by intention to treat. Findings. Time to withdrawal for lack of efficacy or adverse events did not differ between groups (p = 0.318). Vigabatrin was better tolerated than carbamazepine with fewer withdrawals, but was more frequently associated with psychiatric symptoms (58 [25%] vs 34 [15%]) and weight gain (25 [11%] vs 12 [5%]). Carbamazepine was associated with rash (22 [10%] vs seven [3%]). All efficacy outcomes favoured carbamazepine and failed to show equivalence between the two drugs. No significant difference was found for time to achieve 6 months of remission from seizures (p = 0.058), but the most powerful outcome, time to first seizure after the first 6 weeks from randomisation, showed carbamazepine to be significantly more effective than vigabatrin (p = 0.0001). Interpretation. Vigabatrin seems less effective but better tolerated than carbamazepine, which is the first-choice drug for the treatment of partial epilepsies. Vigabatrin cannot therefore be recommended as a first-line drug for monotherapy in this group of patients.

Original languageEnglish
Pages (from-to)13-19
Number of pages7
JournalLancet
Volume354
Issue number9172
DOIs
Publication statusPublished - Jul 3 1999

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Vigabatrin
Carbamazepine
Double-Blind Method
Epilepsy
Seizures
Safety
Pharmaceutical Preparations
Intention to Treat Analysis
Partial Epilepsy
Incidence
Random Allocation
Exanthema
Weight Gain
Psychiatry

ASJC Scopus subject areas

  • Medicine(all)

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Chadwick, D., Baldy-Moulinier, J., Ben-Manachem, E., Beran, R., Bes, A., Biermann, L. D., ... Gomez, G. T. (1999). Safety and efficacy of vigabatrin and carbamazepine in newly diagnosed epilepsy: A multicentre randomised double-blind study. Lancet, 354(9172), 13-19. https://doi.org/10.1016/S0140-6736(98)10531-7

Safety and efficacy of vigabatrin and carbamazepine in newly diagnosed epilepsy : A multicentre randomised double-blind study. / Chadwick, David; Baldy-Moulinier, J.; Ben-Manachem, E.; Beran, R.; Bes, A.; Biermann, L. D.; Bird, J. M.; Boon, L.; Byrne, E.; Calandre, E. P.; de Seijas, E. V.; Tejerina, J. A.; Canger, R.; Saltarelli, A.; Cartlidge, N. E F; Corston, R. N.; Cosi, V.; Dellaportas, C.; Duncan, J.; Van Paesschen, W.; Dam, M.; Danta, G.; Gadot, H.; Gale, A. N.; Gisselbrecht, D.; Gross, M.; Guldenpfennig, W. M.; Haan, J.; Howell, S. J L; Venables, G. S.; Jankovic, J.; Kälviäinen, R.; Riekkinen, P.; Kennedy, K.; Kramer, G.; Kritzinger, P. H.; Manelis, J.; Michelucci, R.; Tassinari, C. A.; Neufeld, M.; Pederson, B.; Pisani, F.; Reches, A.; Ried, B.; Saunders, E. A C M; Somerville, E.; Spechio, L.; Neve, L. A.; Tramacere, L.; Stefan, H.; Tartara, A.; Van As, A. D.; Van Donsellar, C. A.; Weber, M.; Wieser, H. G.; Zaccara, G.; Gomez, G. T.

In: Lancet, Vol. 354, No. 9172, 03.07.1999, p. 13-19.

Research output: Contribution to journalArticle

Chadwick, D, Baldy-Moulinier, J, Ben-Manachem, E, Beran, R, Bes, A, Biermann, LD, Bird, JM, Boon, L, Byrne, E, Calandre, EP, de Seijas, EV, Tejerina, JA, Canger, R, Saltarelli, A, Cartlidge, NEF, Corston, RN, Cosi, V, Dellaportas, C, Duncan, J, Van Paesschen, W, Dam, M, Danta, G, Gadot, H, Gale, AN, Gisselbrecht, D, Gross, M, Guldenpfennig, WM, Haan, J, Howell, SJL, Venables, GS, Jankovic, J, Kälviäinen, R, Riekkinen, P, Kennedy, K, Kramer, G, Kritzinger, PH, Manelis, J, Michelucci, R, Tassinari, CA, Neufeld, M, Pederson, B, Pisani, F, Reches, A, Ried, B, Saunders, EACM, Somerville, E, Spechio, L, Neve, LA, Tramacere, L, Stefan, H, Tartara, A, Van As, AD, Van Donsellar, CA, Weber, M, Wieser, HG, Zaccara, G & Gomez, GT 1999, 'Safety and efficacy of vigabatrin and carbamazepine in newly diagnosed epilepsy: A multicentre randomised double-blind study', Lancet, vol. 354, no. 9172, pp. 13-19. https://doi.org/10.1016/S0140-6736(98)10531-7
Chadwick, David ; Baldy-Moulinier, J. ; Ben-Manachem, E. ; Beran, R. ; Bes, A. ; Biermann, L. D. ; Bird, J. M. ; Boon, L. ; Byrne, E. ; Calandre, E. P. ; de Seijas, E. V. ; Tejerina, J. A. ; Canger, R. ; Saltarelli, A. ; Cartlidge, N. E F ; Corston, R. N. ; Cosi, V. ; Dellaportas, C. ; Duncan, J. ; Van Paesschen, W. ; Dam, M. ; Danta, G. ; Gadot, H. ; Gale, A. N. ; Gisselbrecht, D. ; Gross, M. ; Guldenpfennig, W. M. ; Haan, J. ; Howell, S. J L ; Venables, G. S. ; Jankovic, J. ; Kälviäinen, R. ; Riekkinen, P. ; Kennedy, K. ; Kramer, G. ; Kritzinger, P. H. ; Manelis, J. ; Michelucci, R. ; Tassinari, C. A. ; Neufeld, M. ; Pederson, B. ; Pisani, F. ; Reches, A. ; Ried, B. ; Saunders, E. A C M ; Somerville, E. ; Spechio, L. ; Neve, L. A. ; Tramacere, L. ; Stefan, H. ; Tartara, A. ; Van As, A. D. ; Van Donsellar, C. A. ; Weber, M. ; Wieser, H. G. ; Zaccara, G. ; Gomez, G. T. / Safety and efficacy of vigabatrin and carbamazepine in newly diagnosed epilepsy : A multicentre randomised double-blind study. In: Lancet. 1999 ; Vol. 354, No. 9172. pp. 13-19.
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title = "Safety and efficacy of vigabatrin and carbamazepine in newly diagnosed epilepsy: A multicentre randomised double-blind study",
abstract = "Background. Vigabatrin is a newly licensed drug for use in patients with epilepsy. We investigated whether this drug was comparable to standard first-line monotherapy in efficacy and incidence of adverse events. Methods. We enrolled 459 patients with newly diagnosed, untreated partial epileptic seizures from 44 centres and randomly assigned them carbamazepine 600 mg daily (n = 230) or vigabatrin 2 g daily (n = 229). After initial maintenance doses were reached, doses were adjusted downwards (in the case of adverse events) or upwards (in the case of seizures) by the clinician. The primary outcome was time to withdrawal because of lack of efficacy or adverse events. Secondary outcomes included efficacy (time to 6-month remission of seizures, time to first seizure after initial dose stabilisation), and adverse events (incidence and severity). Analysis was by intention to treat. Findings. Time to withdrawal for lack of efficacy or adverse events did not differ between groups (p = 0.318). Vigabatrin was better tolerated than carbamazepine with fewer withdrawals, but was more frequently associated with psychiatric symptoms (58 [25{\%}] vs 34 [15{\%}]) and weight gain (25 [11{\%}] vs 12 [5{\%}]). Carbamazepine was associated with rash (22 [10{\%}] vs seven [3{\%}]). All efficacy outcomes favoured carbamazepine and failed to show equivalence between the two drugs. No significant difference was found for time to achieve 6 months of remission from seizures (p = 0.058), but the most powerful outcome, time to first seizure after the first 6 weeks from randomisation, showed carbamazepine to be significantly more effective than vigabatrin (p = 0.0001). Interpretation. Vigabatrin seems less effective but better tolerated than carbamazepine, which is the first-choice drug for the treatment of partial epilepsies. Vigabatrin cannot therefore be recommended as a first-line drug for monotherapy in this group of patients.",
author = "David Chadwick and J. Baldy-Moulinier and E. Ben-Manachem and R. Beran and A. Bes and Biermann, {L. D.} and Bird, {J. M.} and L. Boon and E. Byrne and Calandre, {E. P.} and {de Seijas}, {E. V.} and Tejerina, {J. A.} and R. Canger and A. Saltarelli and Cartlidge, {N. E F} and Corston, {R. N.} and V. Cosi and C. Dellaportas and J. Duncan and {Van Paesschen}, W. and M. Dam and G. Danta and H. Gadot and Gale, {A. N.} and D. Gisselbrecht and M. Gross and Guldenpfennig, {W. M.} and J. Haan and Howell, {S. J L} and Venables, {G. S.} and J. Jankovic and R. K{\"a}lvi{\"a}inen and P. Riekkinen and K. Kennedy and G. Kramer and Kritzinger, {P. H.} and J. Manelis and R. Michelucci and Tassinari, {C. A.} and M. Neufeld and B. Pederson and F. Pisani and A. Reches and B. Ried and Saunders, {E. A C M} and E. Somerville and L. Spechio and Neve, {L. A.} and L. Tramacere and H. Stefan and A. Tartara and {Van As}, {A. D.} and {Van Donsellar}, {C. A.} and M. Weber and Wieser, {H. G.} and G. Zaccara and Gomez, {G. T.}",
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TY - JOUR

T1 - Safety and efficacy of vigabatrin and carbamazepine in newly diagnosed epilepsy

T2 - A multicentre randomised double-blind study

AU - Chadwick, David

AU - Baldy-Moulinier, J.

AU - Ben-Manachem, E.

AU - Beran, R.

AU - Bes, A.

AU - Biermann, L. D.

AU - Bird, J. M.

AU - Boon, L.

AU - Byrne, E.

AU - Calandre, E. P.

AU - de Seijas, E. V.

AU - Tejerina, J. A.

AU - Canger, R.

AU - Saltarelli, A.

AU - Cartlidge, N. E F

AU - Corston, R. N.

AU - Cosi, V.

AU - Dellaportas, C.

AU - Duncan, J.

AU - Van Paesschen, W.

AU - Dam, M.

AU - Danta, G.

AU - Gadot, H.

AU - Gale, A. N.

AU - Gisselbrecht, D.

AU - Gross, M.

AU - Guldenpfennig, W. M.

AU - Haan, J.

AU - Howell, S. J L

AU - Venables, G. S.

AU - Jankovic, J.

AU - Kälviäinen, R.

AU - Riekkinen, P.

AU - Kennedy, K.

AU - Kramer, G.

AU - Kritzinger, P. H.

AU - Manelis, J.

AU - Michelucci, R.

AU - Tassinari, C. A.

AU - Neufeld, M.

AU - Pederson, B.

AU - Pisani, F.

AU - Reches, A.

AU - Ried, B.

AU - Saunders, E. A C M

AU - Somerville, E.

AU - Spechio, L.

AU - Neve, L. A.

AU - Tramacere, L.

AU - Stefan, H.

AU - Tartara, A.

AU - Van As, A. D.

AU - Van Donsellar, C. A.

AU - Weber, M.

AU - Wieser, H. G.

AU - Zaccara, G.

AU - Gomez, G. T.

PY - 1999/7/3

Y1 - 1999/7/3

N2 - Background. Vigabatrin is a newly licensed drug for use in patients with epilepsy. We investigated whether this drug was comparable to standard first-line monotherapy in efficacy and incidence of adverse events. Methods. We enrolled 459 patients with newly diagnosed, untreated partial epileptic seizures from 44 centres and randomly assigned them carbamazepine 600 mg daily (n = 230) or vigabatrin 2 g daily (n = 229). After initial maintenance doses were reached, doses were adjusted downwards (in the case of adverse events) or upwards (in the case of seizures) by the clinician. The primary outcome was time to withdrawal because of lack of efficacy or adverse events. Secondary outcomes included efficacy (time to 6-month remission of seizures, time to first seizure after initial dose stabilisation), and adverse events (incidence and severity). Analysis was by intention to treat. Findings. Time to withdrawal for lack of efficacy or adverse events did not differ between groups (p = 0.318). Vigabatrin was better tolerated than carbamazepine with fewer withdrawals, but was more frequently associated with psychiatric symptoms (58 [25%] vs 34 [15%]) and weight gain (25 [11%] vs 12 [5%]). Carbamazepine was associated with rash (22 [10%] vs seven [3%]). All efficacy outcomes favoured carbamazepine and failed to show equivalence between the two drugs. No significant difference was found for time to achieve 6 months of remission from seizures (p = 0.058), but the most powerful outcome, time to first seizure after the first 6 weeks from randomisation, showed carbamazepine to be significantly more effective than vigabatrin (p = 0.0001). Interpretation. Vigabatrin seems less effective but better tolerated than carbamazepine, which is the first-choice drug for the treatment of partial epilepsies. Vigabatrin cannot therefore be recommended as a first-line drug for monotherapy in this group of patients.

AB - Background. Vigabatrin is a newly licensed drug for use in patients with epilepsy. We investigated whether this drug was comparable to standard first-line monotherapy in efficacy and incidence of adverse events. Methods. We enrolled 459 patients with newly diagnosed, untreated partial epileptic seizures from 44 centres and randomly assigned them carbamazepine 600 mg daily (n = 230) or vigabatrin 2 g daily (n = 229). After initial maintenance doses were reached, doses were adjusted downwards (in the case of adverse events) or upwards (in the case of seizures) by the clinician. The primary outcome was time to withdrawal because of lack of efficacy or adverse events. Secondary outcomes included efficacy (time to 6-month remission of seizures, time to first seizure after initial dose stabilisation), and adverse events (incidence and severity). Analysis was by intention to treat. Findings. Time to withdrawal for lack of efficacy or adverse events did not differ between groups (p = 0.318). Vigabatrin was better tolerated than carbamazepine with fewer withdrawals, but was more frequently associated with psychiatric symptoms (58 [25%] vs 34 [15%]) and weight gain (25 [11%] vs 12 [5%]). Carbamazepine was associated with rash (22 [10%] vs seven [3%]). All efficacy outcomes favoured carbamazepine and failed to show equivalence between the two drugs. No significant difference was found for time to achieve 6 months of remission from seizures (p = 0.058), but the most powerful outcome, time to first seizure after the first 6 weeks from randomisation, showed carbamazepine to be significantly more effective than vigabatrin (p = 0.0001). Interpretation. Vigabatrin seems less effective but better tolerated than carbamazepine, which is the first-choice drug for the treatment of partial epilepsies. Vigabatrin cannot therefore be recommended as a first-line drug for monotherapy in this group of patients.

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