What Are The Long-Term Neurological And Cognitive Outcomes Of Various Pharmacological Interventions For Patients With Chronic Epilepsy? : A Systematic Review
Keywords:
Epilepsy, Antiepileptic drugs, Long-term outcomes, Cognitive function, Neurological outcomesAbstract
Introduction: Epilepsy is a chronic neurological disorder characterized by recurrent seizures, significantly impacting patients' quality of life. The management of epilepsy primarily involves pharmacological interventions aimed at reducing seizure frequency and improving neurological function. Recent advancements in antiepileptic drugs (AEDs) have provided new options, particularly for patients with refractory epilepsy. Methods: This systematic review evaluated the long-term neurological and cognitive outcomes of various pharmacological interventions for adults with chronic epilepsy. Studies were included if they involved adult participants, examined AEDs, measured cognitive or neurological outcomes, and had a follow-up period of at least 12 months. A comprehensive search was conducted across multiple databases, yielding 40 relevant studies. Results: The findings indicate that newer AEDs, such as brivaracetam and cenobamate, demonstrate significant efficacy in reducing seizure frequency, with median reductions ranging from 48.8% to 78%. However, cognitive effects varied; while some medications like topiramate had low incidences of cognitive adverse events, others such as carbamazepine were associated with declines in cognitive function. Discussion: The interplay between seizure control and cognitive outcomes is complex. Improved seizure management may lead to positive neurological adaptations, although certain AEDs can adversely affect cognitive function. The variability in outcomes underscores the need for individualized treatment approaches based on patient-specific factors. Conclusion: Long-term pharmacotherapy for epilepsy reveals a dual narrative of efficacy and cognitive impact. While advancements have improved seizure control, careful consideration of cognitive side effects is essential for optimizing patient outcomes.
References
A. Alfaro, M. Asensio, A. García-Escrivá, V. Medrano, J. M. Salom, D. Tortosa, S. Palao, et al. “LAM Study: Effects of Lacosamide on Behaviour and Quality of Life in Patients with Epilepsy.” Neurología, 2016.
A. Ben. “Carphology.” Practical Neurology, 2024.
A. Jesse, Valerie Alipio-Jocson, Katherine Inoyama, Victoria Bartlett, S. Sandhu, J. Oso, J. Barry, D. Loring, and K. Meador. “Methylphenidate's Effects on Cognition in Patients with Epilepsy: A Randomized, Double-Blind, Placebo-Controlled, Crossover, Single-Dose Study (S22.002).” Neurology, 2016.
A. Lasek-Bal, Barbara Kściuk, Tomasz Zieliński, Agnieszka Krzak-Kubica, Jacek Kowalski, Barbara Żorniak- Milach, Katarzyna Maciejowska, Maciej Maciejowski, Anna Wagner-Kusz, and Magdalena Bosak. “Long- Term Cenobamate Retention, Efficacy, and Safety: Outcomes from Expanded Access Programme.” Neu- rologia i Neurochirurgia Polska, 2023.
A. Thelengana, G. Shukla, A. Srivastava, Mamta B. Singh, Anupama Gupta, R. Rajan, D. Vibha, A. Pandit, and K. Prasad. “Cognitive, Behavioural and Sleep-Related Adverse Effects on Introduction of Levetiracetam Versus Oxcarbazepine for Epilepsy.” Epilepsy Research, 2019.
B. Moseley, S. Dimova, S. Elmoufti, C. Laloyaux, and A. Asadi-Pooya. “Long-Term Efficacy and Tolerabil- ity of Adjunctive Brivaracetam in Adults with Focal to Bilateral Tonic-Clonic (Secondary Generalized) Seizures: Post Hoc Pooled Analysis.” Epilepsy Research, 2021.
Christopher S. Pauli, Matthieu Conroy, B. V. Vanden Heuvel, and Sang-Hyuck Park. “Cannabidiol Drugs Clinical Trial Outcomes and Adverse Effects.” Frontiers in Pharmacology, 2020.
Christopher T. Buckley, Olivia R Waters, and G. Demaagd. “Cenobamate: A New Adjunctive Agent for Drug-Resistant Focal Onset Epilepsy.” The Annals of Pharmacotherapy, 2020.
D. Franz, J. Lawson, Z. Yapıcı, H. Ikeda, T. Polster, R. Nabbout, P. Curatolo, et al. “Adjunctive Everolimus Therapy for Tuberous Sclerosis Complex‐associated Refractory Seizures: Results from the Postextension Phase of EXIST‐3.” Epilepsia, 2021.
D. Kansal, N. Patiyal, A. Bhardwaj, A. Sood, Sushma Sawaraj, Ankit Chauhan, and Palvi Mittal. “A Comparative Study of the Safety, Efficacy, Quality of Life and Pharmacoeconomics of Levetiracetam with Controlled-Release Carbamazepine in Patients of New Onset Focal Seizures: A Randomized Controlled Academic Trial,” 2021.
D. Krueger, A. Wilfong, M. Mays, Christina Talley, K. Agricola, C. Tudor, Jamie K. Capal, K. Holland- Bouley, and D. Franz. “Long-Term Treatment of Epilepsy with Everolimus in Tuberous Sclerosis.” Neu- rology, 2016.
E. Ben-Menachem, H. Grebe, K. Terada, L. Jensen, Ting Li, M. De Backer, B. Steiniger-Brach, T. Gasalla, Melissa Brock, and V. Biton. “Long‐term Safety and Efficacy of Lacosamide and Controlled‐release Carbamazepine Monotherapy in Patients with Newly Diagnosed Epilepsy.” Epilepsia, 2019.
E. Ben-Menachem, Jacqueline Domínguez, J. Szász, C. Beller, Charles Howerton, L. Jensen, Carrie McClung, R. Roebling, and B. Steiniger-Brach. “Long‐term Safety and Tolerability of Lacosamide Monotherapy in Patients with Epilepsy: Results from a Multicenter, Open‐label Trial.” Epilepsia Open, 2021.
E. Faught. “Measure for Measure: Measuring the Usefulness of Measuring Antiseizure Medication Levels.” Epilepsy Currents, 2020.
E. Thiele, E. Marsh, M. Mazurkiewicz-Bełdzińska, J. Halford, B. Gunning, O. Devinsky, D. Checketts, and Claire Roberts. “Cannabidiol in Patients with Lennox‐Gastaut Syndrome: Interim Analysis of an Open‐label Extension Study.” Epilepsia, 2019.
F. Gilliam, Hailong Cheng, and D. Blum. “Changes in Quality of Life (QoL) and Depressive Symptoms in a Long-Term Open-Label Extension (OLE) of Eslicarbazepine Acetate (ESL) Monotherapy Studies in Adults with Refractory Partial-Onset Seizures (POS) (P1.234).” Neurology, 2015.
F. Hlebokazov, T. Dakukina, M. Potapnev, S. Kosmacheva, L. Moroz, N. Misiuk, T. Golubeva, et al. “Clin- ical Benefits of Single Vs Repeated Courses of Mesenchymal Stem Cell Therapy in Epilepsy Patients.” Clinical Neurology and Neurosurgery (Dutch-Flemish Ed. Print), 2021.
G. Ahmed, Khaled A. M. Elbeh, Y. Elserogy, and S. Mostafa. “Effect of Long-Term Administration of Clonazepam, Carbamazepine, and Valproate on Cognitive, Psychological, and Personality Changes in Adult Epilepsy: A Case–Control Study.” Middle East Current Psychiatry, 2021.
G. Mbizvo, Glen P. Martin, M. Sperrin, L. Bonnett, Pieta Schofield, I. Buchan, G. Y. Lip, and Anthony G Marson. “An International Study to Investigate and Optimise the Safety of Discontinuing Valproate in Young Men and Women with Epilepsy: Protocol.” medRxiv, 2024.
Gagandeep Singh, S. Sharma, N. Bansal, Meenakshi Sharma, Anuraag Chowdhury, Sarit Sharma, R. Bansal, et al. “A Cluster‐randomized Trial Comparing Home‐based Primary Health Care and Usual Clinic Care for Epilepsy in a Resource‐limited Country.” Epilepsia Open, 2022.
I. Blatt, Steve S. Chung, B. Lawson, Huy A. Nguyen, V. Yu, Mary Holmay, Mark B. Halvorsen, and R. Hogan. “Neurocognitive Adverse Event Profile of USL255 (Qudexy® XR; Topiramate Extended-Release Capsules): Phase 3 PREVAIL and PREVAIL OLE Studies (P4.222).” Neurology, 2016.
J. Adams, Valerie Alipio-Jocson, Katherine Inoyama, Victoria Bartlett, S. Sandhu, J. Oso, J. Barry, D. Loring, and K. Meador. “Methylphenidate, Cognition, and Epilepsy: A 1‐month Open‐label Trial.” Epilepsia, 2017.
J. Szaflarski, O. Devinsky, Merrick Lopez, Yong-Deok Park, P. P. Zentil, Anup D. Patel, E. Thiele, R. Wechsler, D. Checketts, and F. Sahebkar. “Long‐term Efficacy and Safety of Cannabidiol in Patients with Treatment‐resistant Epilepsies: Four‐year Results from the Expanded Access Program.” Epilepsia, 2022.
Javid Shafiyev, and Ömer Karadaş. “The Assessment of the Impact of Antiepileptic Drugs on Cognitive Functions via N-200/P-300 Potentials and Neuropsychological Measures.” Neurological Sciences, 2024.
K. Meador, D. Loring, Tara L. Skarpaas, and M. Morrell. “Interictal Spike Rates Are Correlated with Verbal Memory in Patients with Mesial Temporal Lobe Epilepsy (S11.004).” Neurology, 2018.
L. Vivash, Hannah T Johns, Leonid Churilov, Sara MacPhail, Pablo M. Casillas-Espinosa, Charles B Malpas, Sandy R. Shultz, et al. “Phase II Randomised Placebo-Controlled Trial of Sodium Selenate as a Disease- Modifying Treatment in Chronic Drug-Resistant Temporal Lobe Epilepsy: The SeLECT Study Protocol.” BMJ Open, 2023.
M. Rademacher, M. Toledo, W. van Paesschen, K. Liow, I. Milanov, Maria-Luise Esch, Nan Wang, et al. “Efficacy and Safety of Adjunctive Padsevonil in Adults with Drug‐resistant Focal Epilepsy: Results from Two Double‐blind, Randomized, Placebo‐controlled Trials.” Epilepsia Open, 2022.
M. Toledo, Patrick S L Kwan, Martin E. Johnson, S. Borghs, K. Eckhardt, J. Schiemann, and J. Whitesides. “Seizure and Quality of Life Outcomes in Patients with Long-Term Adjunctive Brivaracetam Treatment for Partial-Onset Seizures (P2.032).” Neurology, 2016.
Natalia Molodozhnikova, Svetlana Prokhorova, D. Monov, and Nikolay Lilyanov. “Neurological and Cogni- tive Effects of Hypothyroidism in Patients With Epilepsy: A Study on Anti-Seizure Medicines Therapy.” Journal of Neuroscience Research, 2025.
Quentin Calonge, Aurore Besnard, Laurent Bailly, Maria Damiano, P. Pichit, S. Dupont, Isabelle Gourfinkel- An, and Vincent Navarro. “Cannabidiol Treatment for Adult Patients with Drug‐Resistant Epilepsies: A Real‐World Study in a Tertiary Center.” Brain and Behavior, 2024.
R. Hogan, I. Blatt, Annie M. Clark, B. Anders, Mark B. Halvorsen, and Steve S. Chung. “Long-Term Efficacy, Safety, and Impact on Quality of Life of USL255, Qudexy™ XR (Topiramate) Extended-Release Capsules: PREVAIL OLE (P1.247).” Neurology, 2015.
S. Burd, A. Lebedeva, N. V. Pantina, Y. Rubleva, N. V. Pizova, S. V. Vasil’ev, A. Belova, et al. “[Clin- ical Results and Prospects for the Use of Phenosanic Acid in Patients with Focal Epilepsy].” Zhurnal Nevrologii i Psikhiatrii Imeni S.S. Korsakova, 2021.
S. Sharma, Anuraag Chowdhury, Dr. Sarit Sharma, R. Bansal, and Gagandeep Singh. “A Home-Based, Primary-Care Model for Epilepsy Care in Low and Middle Income Countries: Basis and Design.” Inter- national Journal of Epilepsy, 2018.
Sami Aboumatar, Louis Ferrari, Sean Stern, C. Wade, Mindl M. Weingarten, Gregory S. Connor, and William E. Rosenfeld. “Reductions in Concomitant Antiseizure Medication Drug Load During Adjunctive Cenobamate Therapy: Post-Hoc Analysis of a Subset of Patients from a Phase 3, Multicenter, Open-Label Study.” Epilepsy Research, 2024.
Sang Kun Lee, Sang Ahm Lee, Seung Bong Hong, Yong-won Cho, Guillermo Castilla-Fernández, Miguel M Fonseca, J. Moreira, Helena Gama, and Joerg Holenz. “Long‐term Effects of Adjunctive Eslicarbazepine Acetate in Adult Asian Patients with Refractory Focal Seizures: Post Hoc Analysis of a Phase III Trial.” Clinical and Translational Science, 2024.
Steve S. Chung, J. French, G. Krauss, S. Lee, M. Maciejowski, W. Rosenfeld, M. Sperling, and M. Kamin. “Long-Term Safety of Adjunctive Cenobamate in Patients with Uncontrolled Focal Seizures: Open-Label Extension of a Randomized Clinical Study (1039).” Neurology, 2020
Steve S. Chung, S. Sinha, Aashit Shah, J. Stern, Hailong Cheng, JungAh Jung, T. Grinnell, and D. Blum. “Long-Term Safety and Efficacy Following Conversion to Eslicarbazepine Acetate Monotherapy in Adults with Focal Seizures.” Epilepsy Research, 2019.
T. O’Brien, S. Borghs, Q. He, Anne-Liv Schulz, Stephen L. Yates, and V. Biton. “Long‐term Safety, Effi- cacy, and Quality of Life Outcomes with Adjunctive Brivaracetam Treatment at Individualized Doses in Patients with Epilepsy: An up to 11‐year, Open‐label, Follow‐up Trial.” Epilepsia, 2020.
V. Franco, M. Canevini, G. De Sarro, C. Fattore, G. Fedele, C. A. Galimberti, G. Gatti, et al. “Does Screening for Adverse Effects Improve Health Outcomes in Epilepsy?” Neurology, 2020.
Zhaomin Xie, Xue-feng Li, Junxiong Yin, Min Wang, Xiaohang Fan, Jin-Gang Yu, Duyanlu Wang, Yunyi Li, and Mengting Yu. “Value of Group Intervention on Prognosis of Quality of Life in Epileptic Patients Treated With Sodium Valproate and Lamotrigine.” Alternative Therapies in Health and Medicine, 2023
Downloads
Published
Issue
Section
License
Copyright (c) 2025 Mohammad Jathy Oktariansyah, Fifa Yuniarmi, Kanuyasa Widyatama, Alestya Putri Jathy (Author)
This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.
Authors publishing here keep copyright but grant the journal first publication rights, under a Creative Commons Attribution-NonCommercial 4.0 License. They can distribute their work non-exclusively elsewhere with an acknowledgment of its first publication in this journal. Posting the work online before and during submission for earlier and greater citation is encouraged, reflecting Open Access benefits.
