An International Multicenter Randomized Double‐Blind Controlled Trial of Lamotrigine and Sustained‐Release Carbamazepine in the Treatment of Newly Diagnosed Epilepsy in the Elderly

Sætre, Erik; Perucca, Emilio; Isojärvi, Jouko; Gjerstad, Leif

doi:10.1111/j.1528-1167.2007.01128.x

Cited by 199 publications

(132 citation statements)

References 36 publications

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“…In 2007, Saetre and colleagues reported findings in 185 adults aged 65 years or older who were randomized to treatment with CBZ-CR or LTG and followed over 40 weeks (4). In this study, the primary measure, retention on AED over the course of the study, did not differ between the two drugs.…”

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confidence: 54%

Giving an Older Patient Newer Drugs

Spencer¹

2015

Epilepsy Curr

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CommentaryIt is often observed that children are not just small adults. They are physiologically different in many ways, including in drug metabolism and susceptibility to idiosyncratic side effects of drugs. At the other end of the life span, similar observations can be made regarding how older adults differ from their younger adult counterparts. These differences at each end of the age spectrum are especially pertinent to the treatment of epilepsy, which has a bimodal distribution of incidence, with peaks in the young and old. The largest and fastest growing peak is in older adults, with one estimate suggesting that half of all epilepsy may be in adults over age 60 by the year 2020 (1).As the pace of new antiepileptic drug (AED) development accelerated in the 1990s, new algorithms for selecting AEDs had to be developed on the basis of relatively few comparative AED trials. A few of these trials focused on determining the optimal choice of AED for older patients. In 1999, Brodie and colleagues reported findings in 150 older adults with new-onset epilepsy who were randomized to treatment with immediate release carbamazepine (CBZ-IR)-the de facto standard for treatment of partial seizures at the time-or lamotrigine (LTG) (2). The primary outcome measure was retention on the randomly selected AED over the 24-week study. The findings were striking-the CBZ-treated subjects were more than twice as likely to come off of therapy, and the greater attrition in the CBZ group was nearly all accounted for by poorer tolerability. The importance of tolerability was emphasized by the larger US Department of Veterans Affairs (VA) cooperative study of epilepsy in the elderly, which compared CBZ-IR, LTG, and also gabapentin (GBP) using a similar survival analysis (3). Although efficacy did not greatly vary among the AEDs studied, there were significant differences in tolerability, again with more dropouts because of adverse effects in the CBZ-IR group than the others.As the use of controlled-release CBZ (CBZ-CR) preparations became more common, many argued that the correct comparison with newer AEDs should be with the better-tolerated CBZ-CR. In 2007, Saetre and colleagues reported findings in 185 adults aged 65 years or older who were randomized to treatment with CBZ-CR or LTG and followed over 40 weeks (4). In this study, the primary measure, retention on AED over the course of the study, did not differ between the two drugs. Similarly, time to withdrawal and proportion of seizure-free pa- OBJECTIVE: To compare the effectiveness of controlled-released carbamazepine (CR-CBZ) to levetiracetam (LEV) and to lamotrigine (LTG) in elderly patients with newly diagnosed focal epilepsy. METHODS: Randomized, double-blind, parallel-group trial conducted between January 2007 and August 2011, in 47 ambulatory or hospital sites in Germany, Austria, or Switzerland. Eligible participants were aged ≥60, had new-onset epilepsy, had no acute illness as the cause of their seizures, and had no contraindication to the drugs in the trial. Patients wer...

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confidence: 54%

Giving an Older Patient Newer Drugs

Spencer¹

2015

Epilepsy Curr

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“…[17] Başka bir araştırmada ise çocuklarda ve yaşlılarda parsiyel başlangıçlı epilepsilerde lamotrijinin karbamazepine göre daha iyi tolere edildiği bildirilmiştir. [18] Saetre ve ark.nın [19] bir çalışmasında ise karbamazepinle nöbetsizlik oranlarının daha yüksek olduğu, lamotrijinin ise daha iyi tolere edildiği gösterilmiştir. International League Against Epilepsy (ILAE) yeni tanı veya tedavi edilmemiş parsiyel baş-langıçlı nöbetleri olan yaşlılarda gabapentin ve lamotrijini etkili ve etkin olduğunu bildirdi.…”

Section: Discussionunclassified

Epilepsy in elderly patients

Halaç¹

2015

Epilepsi

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SummaryObjectives: The incidence of new-onset epilepsy is high among the elderly. This study presents the demographic characteristics, etiological factors, seizure types and response rates to treatment in a group of patients aged 65 years or over with delayed-onset epilepsy. Methods:The study comprised a retrospective evaluation of the records of 43 patients aged 65 or older with a diagnosis of delayed-onset epilepsy who were admitted to the epilepsy clinic in the Neurology Department of Bezmialem University Faculty of Medicine.Results: Patient mean age was 74.9 (66-92 years). Underlying disease was found to be cerebrovascular disease in 37.2%. Based on seizure type, 67.4% (n=29) patients had partial-onset and 32.6% (n=14) had generalized seizure. Treatment protocol in 93% (n=40) of the patients was monotherapy antiepileptic drugs, the most commonly used being levetiracetam (53.5%). Assessment of drug side effects showed no complaint in 86% (n=37) of the patients. During the three months prior to the study, 95.3% of the patients had been seizure free. Conclusion:The study found cerebrovascular disease to be the most common etiological factor in delayed-onset epilepsy. Partial-onset secondary generalized seizure was the most common seizure type. All patients responded well to monotherapy and have a good prognosis.Key words: Epilepsy; treatment; elderly patients. ÖzetAmaç: Yaşlılarda yeni başlangıçlı epilepsi insidansı oldukça yüksektir. Çalışmada, 65 yaş üstü geç başlangıçlı epilepsi tanısı alan hastaların demografik özellikleri, etiyolojik faktörleri, nöbet tipleri ve tedaviye yanıt oranları sunulmuştur ve literatür eşliğinde sonuçlar tartışılmıştır. Sonuç: Geç başlangıçlı epilepsi hastalarında en sık görülen etiyolojik neden serebrovasküler hastalık olup nöbet tipi çoğunlukla parsiyel başlangıçlı sekonder jeneralize tonik kloniktir, hastalar monoterapiye iyi yanıt verir ve prognoz iyi seyirlidir. Gereç ve

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“…2). 55, 56 Both trials used a very similar design and dosing schedules, but the formulation of carbamazepine differed. Whereas retention in the trial (primary outcome) in the lamotrigine arm was almost identical in the two trials, for carbamazepine the outcome was markedly better when the controlled‐release formulation was used, mainly because of improved tolerability.…”

Section: Randomized Controlled Trialsmentioning

confidence: 99%

“…Retention in the trial (a combined measure of efficacy and tolerability) in two double‐blind RCT s comparing the outcome of treatment with lamotrigine and carbamazepine ( CBZ ) monotherapy in patients aged 65 years and over with newly diagnosed epilepsy with onset in old age 55, 56. Outcome with lamotrigine was similar in the two trials, whereas outcome on carbamazepine was better in the trial that used the controlled‐release formulation.…”

Section: Randomized Controlled Trialsmentioning

confidence: 99%

Not all that glitters is gold: A guide to the critical interpretation of drug trials in epilepsy

Perucca

Wiebe

2016

Epilepsia Open

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SummaryClinical trials represent the best source of evidence on which to base treatment decisions. For such evidence to be utilized meaningfully, however, it is essential that results are interpreted correctly. This requires a good understanding of strengths and weaknesses of the adopted design, the clinical relevance of the outcome measures, and the many factors that could affect such outcomes. As a general rule, uncontrolled studies tend to provide misleading evidence as a result of the impact of confounders such as regression to the mean, patient‐related bias, and observer bias. On the other hand, although randomized controlled trials (RCTs) are qualitatively superior, aspects of their execution may still decrease their validity. Bias and decreased validity in RCTs may occur by chance alone (for example, treatment groups may not necessarily be balanced for important variables despite randomization) or because of specific features of the trial design. In the case of industry‐driven studies, bias often influences the outcome in favor of the sponsor's product. Factors that need to be carefully scrutinized include (1) the purpose for which the trial is conducted; (2) potential bias due to unblinding or lack of blinding; (3) the appropriateness of the control group; (4) the power of the study in detecting clinically relevant differences; (5) the extent to which eligibility criteria could affect outcomes and be representative of routine clinical practice; (6) whether the treatments being compared are used optimally in terms of dosing, duration of treatment, and other variables; (7) the appropriateness of the statistical comparisons; (8) the clinical relevance of the outcome measures and whether all key outcome information is reported (for example, responder rates in completers); and (9) potential bias in the way results are presented and discussed. This article discusses each of these aspects and illustrates the discussion with examples taken from published antiepileptic drug trials.

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An International Multicenter Randomized Double‐Blind Controlled Trial of Lamotrigine and Sustained‐Release Carbamazepine in the Treatment of Newly Diagnosed Epilepsy in the Elderly

Cited by 199 publications

References 36 publications

Giving an Older Patient Newer Drugs

Giving an Older Patient Newer Drugs

Epilepsy in elderly patients

Not all that glitters is gold: A guide to the critical interpretation of drug trials in epilepsy

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