A randomized double-blind placebo-controlled add-on trial of lamotrigine in patients with severe epilepsy

Sander, Josemir W.; Patsalos, Philip N.; Oxley, J; Hamilton, M. J.; Yuen, W. C.

doi:10.1016/0920-1211(90)90077-9

Cited by 135 publications

(38 citation statements)

References 14 publications

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“…LTG had no clinically significant effect on the plasma concentrations of any concomitantly administered AED during the study, a finding that confirms the results of previous studies (Binnie et al, 1989;Jawad et al, 1989;Sander et al, 1990). Thus, LTG can easily be added to an ongoing AED regimen without the need for major adjustments in concomitant AED dosages.…”

Section: Discussionsupporting

confidence: 88%

Lamotrigine Therapy for Partial Seizures: A Multicenter, Placebo‐Controlled, Double‐Blind, Cross‐Over Trial

et al. 1994

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The efficacy and safety of lamotrigine (LTG), a new antiepileptic drug (AED), were evaluated in a multicenter, randomized, double-blind, placebo-controlled, cross-over study of 98 patients with refractory partial seizures. Each treatment period lasted 14 weeks. Most patients were titrated to a LTG maintenance dose of 400 mg/day. Seizure frequency with LTG decreased by > or = 50%, as compared with placebo, in one fifth of patients. Overall median seizure frequency decreased by 25% with LTG as compared with placebo (p < 0.001). With LTG, the number of seizure days decreased by 18% as compared with placebo (p < 0.01), and investigator global evaluation of overall patient clinical status favored LTG by 2:1 (p = 0.013). Plasma LTG concentrations appeared to be linearly related to dosage. LTG had no clinically important effects on the plasma concentrations of concomitant AEDs. Adverse experiences were generally minor and most frequently were CNS-related (e.g., ataxia, dizziness, diplopia, headache). Most were transient and resolved without discontinuing treatment. Five patients withdrew as a result of adverse experiences while receiving LTG, including 3 patients with rash. One placebo patient was also withdrawn because of rash. The addition of twice-daily LTG to an existing AED regimen was safe, effective, and well tolerated in these medically refractory partial seizure patients.

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Section: Discussionsupporting

confidence: 88%

Lamotrigine Therapy for Partial Seizures: A Multicenter, Placebo‐Controlled, Double‐Blind, Cross‐Over Trial

et al. 1994

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“…Three studies included only patients with generalised onset seizures, 76,79,134 and 13 studies included patients with partial or generalised seizures. 51,[82][83][84][85][86]88,131,[135][136][137][138][139] The proportion of participants with each seizure type was often not reported in studies of mixed seizure types and similarly outcome data were not reported separately for each of the different seizure type. The relevance of these data to individual seizure types was unclear.…”

Section: [Data Have Been Designated Commercial-inconfidence and Have mentioning

confidence: 99%

Clinical effectiveness, tolerability and cost-effectiveness of newer drugs for epilepsy in adults: a systematic review and economic evaluation

Wilby¹,

Kainth²,

Hawkins³

et al. 2005

Health Technol Assess

199

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“…In seven articles, two treatments were compared and the number of AE effects and the average dose or serum level of every AED was reported per treatment group (27)(28)(29)(30)(31)(32)(33). We calculated the mean total AED loads or OSL/AToxL ratio per treatment group (Table 2) with the respective number of AE reported.…”

Section: A E and Doseherum Levels Reported Per Treatment Groupmentioning

confidence: 99%

Reappraisal of Polytherapy in Epilepsy: A Critical Review of Drug Load and Adverse Effects

et al. 1997

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Summary: Purpose:We reviewed the literature to determine whether an analysis of published data could clarify the relationship between antiepileptic drug (AED) polytherapy and adverse affects (AE). We highlight the problems encountered.Methods: We made a Medline-search for articles published between 1974 and 1994 reporting the number of AE and doses or serum levels of every AED, per patient or treatment group, and used the PDD/DDD ratio to calculate AED load per patient from doses or the OSL/AToxL ratio to do so from serum levels of individual drugs. The PDD/ DDD is the sum of ratios of the actual prescribed daily doses divided by the published average therapeutic dose of each drug. The OSL/AToxL is the sum of each observed serum level divided by its average toxic level.Results: We retrieved 118 trial reports. Most had to be excluded because of incomplete reporting of concomitant medication or AE. The data of the 15 articles selected for further analysis indicate a relationship between drug load and number of AE. We noted no relationship between the number of AEDs administered and AE. In add-on studies, the difference in neurotoxicity between the active and placebo arm may be obscured if the relative increase in drug load is small, as exemplified by the study of McGuire et al. (35).Conclusions: Articles reporting add-on trials of new AEDs generally do not provide detailed information about the basic medication to which the new AED is added, which makes calculation of total drug load impossible. Furthermore, often only frequency of A E is reported, not severity or development of tolerance, making it difficult to judge the impact of AE. However, despite the paucity of available information, we present some evidence that toxicity in AED polytherapy may be related to total drug load, rather than to the number of drugs administered. Therefore, the present trend to reject polytherapy for fear of increased toxicity is not warranted, which removes one of the objections to initiating specific research to prove or disprove the value of AED combinations as long as the drug load is appropriate. Key Words: PolytherapyAntiepileptic drugs-Adverse effects-Drug loadEpilepsy.Antiepileptic drug (AED) pharmacotherapy is aimed at reducing seizure frequency and severity without producing adverse effects (AE). However, the reporting of AE in clinical trials lacks quantitative data because AE are often described in terms of frequency and rarely in terms of severity (1). Although the incidence of AE is important, the degree to which they occur also determines the acceptability of individual AEDs. When quantitative data are presented, a comparison is complicated because of the different rating scales used (2,3).The risk of development of chronic toxicity has been one of the arguments against use of polypharmacy in epilepsy (4). Much of this toxicity is believed Accepted January 13, 1997. Address correspondence and reprint requests to Dr. H. Meinardi, c/o P.O. Box 21,2100 AA Heemstede, The Netherlands.to be directly related to the number ...

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A randomized double-blind placebo-controlled add-on trial of lamotrigine in patients with severe epilepsy

Cited by 135 publications

References 14 publications

Lamotrigine Therapy for Partial Seizures: A Multicenter, Placebo‐Controlled, Double‐Blind, Cross‐Over Trial

Lamotrigine Therapy for Partial Seizures: A Multicenter, Placebo‐Controlled, Double‐Blind, Cross‐Over Trial

Clinical effectiveness, tolerability and cost-effectiveness of newer drugs for epilepsy in adults: a systematic review and economic evaluation

Reappraisal of Polytherapy in Epilepsy: A Critical Review of Drug Load and Adverse Effects

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