Outcome prediction of initial lamotrigine monotherapy in adult patients with newly diagnosed localization related epilepsies

Stevo Lukić; Nebojša Jović; Zoran Milošević; Bojko Bjelaković; Zoran Perić; Mirjana Spasić

doi:10.1016/j.eplepsyres.2013.11.008

Outcome prediction of initial lamotrigine monotherapy in adult patients with newly diagnosed localization related epilepsies

Epilepsy Res. 2014 Feb;108(2):295-304. doi: 10.1016/j.eplepsyres.2013.11.008. Epub 2013 Nov 17.

Authors

Stevo Lukić¹, Nebojša Jović², Zoran Milošević³, Bojko Bjelaković⁴, Zoran Perić⁵, Mirjana Spasić⁵

Affiliations

¹ Clinic of Neurology, Clinical centre Niš, Serbia; Faculty of Medicine, University of Niš, Serbia. Electronic address: srlukic@gmail.com.
² Clinic of Neurology and Psychiatry for Children and Youth, School of Medicine, University of Belgrade, Serbia; Faculty of Medicine, University of Belgrade, Serbia.
³ Faculty of Medicine, University of Niš, Serbia; Department of medical statistic and informatics, Institute of Public Health, Niš, Serbia.
⁴ Faculty of Medicine, University of Niš, Serbia; Clinic of Pediatrics, University Clinical Center Niš, Serbia.
⁵ Clinic of Neurology, Clinical centre Niš, Serbia; Faculty of Medicine, University of Niš, Serbia.

PMID: 24314596
DOI: 10.1016/j.eplepsyres.2013.11.008

Abstract

Objective: To develop and test model to predict outcome of treatment with initial lamotrigine monotherapy in adult patients with newly diagnosed localization - related epilepsy, using data available at the time of diagnosis.

Methods: Prospective longitudinal study included consecutive series of adult patients with newly diagnosed localization - related epilepsy started of lamotrigine monotherapy. Logistic regression analysis using backward procedure was performed with treatment failure as the outcome variable. We evaluated both calibration and discrimination of the model. Internal validation of the model was performed with bootstrapping techniques.

Results: A total of 159 patients on lamotrigine monotherapy have been included in final analysis. Among them 78 (49.06%) patients had persistent seizures. Finally fitted multivariate model included: 1) age at therapy start, 2) presence of complex partial seizures, 3) aetiology of epilepsy and 4) interaction of age and epilepsy aetiology. Estimated odds ratio for seizure relapse in old patients with symptomatic epilepsy is lower than for the old patients with cryptogenic epilepsy, despite strong positive covariate effect of epilepsy aetiology. The model correctly classified 69.23% patients with seizure relapses and 81.48% of patients with seizure freedom, with estimated c - statistic of 0.80. Testing practical application we observed threefold increase or reduction of odds for the seizure relapse after model's positive or negative prediction respectively.

Conclusion: Standard clinical data were modesty adequate to predict response to the initial trial of lamotrigine in adult patients with localization related epilepsy. Better markers of antiepileptic failure are required to guide optimal patient counselling and clinical decisions. Formal interaction analysis of variables improves outcome prediction and may be a key to correct interpretation of data.

Keywords: Effect modifiers; Epilepsy; Lamotrigine; Prognosis; Treatment outcome.

MeSH terms

Adult
Anticonvulsants / administration & dosage*
Epilepsies, Partial / diagnosis*
Epilepsies, Partial / drug therapy*
Female
Follow-Up Studies
Humans
Lamotrigine
Longitudinal Studies
Male
Middle Aged
Predictive Value of Tests
Prospective Studies
Registries
Treatment Outcome
Triazines / administration & dosage*

Substances

Anticonvulsants
Triazines
Lamotrigine