Add‐on treatment with vinpocetine reduces seizure frequency and improves comorbidities in patients with loss‐of‐function γ‐aminobutyric acid type A receptor variants
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Wiley
2026
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| author | Cathrine E. Gjerulfsen Vivian W. Y. Liao Tomasz S. Mieszczanek Anne V. Jakobsen Elena Gardella Kern Olofsson Marina Nikanorova Allan Bayat Sebastian Ortiz Sarah Weckhuysen Cecilie Johannessen Landmark Orrin Devinsky Mary Chebib Philip K. Ahring Guido Rubboli Rikke S. Møller |
| author_facet | Cathrine E. Gjerulfsen Vivian W. Y. Liao Tomasz S. Mieszczanek Anne V. Jakobsen Elena Gardella Kern Olofsson Marina Nikanorova Allan Bayat Sebastian Ortiz Sarah Weckhuysen Cecilie Johannessen Landmark Orrin Devinsky Mary Chebib Philip K. Ahring Guido Rubboli Rikke S. Møller Cathrine E. Gjerulfsen Vivian W. Y. Liao Tomasz S. Mieszczanek Anne V. Jakobsen Elena Gardella Kern Olofsson Marina Nikanorova Allan Bayat Sebastian Ortiz Sarah Weckhuysen Cecilie Johannessen Landmark Orrin Devinsky Mary Chebib Philip K. Ahring Guido Rubboli Rikke S. Møller |
| collection | Wiley Open Access |
| contents | Add‐on treatment with vinpocetine reduces seizure frequency and improves comorbidities in patients with loss‐of‐function γ‐aminobutyric acid type A receptor variants Cathrine E. Gjerulfsen Vivian W. Y. Liao Tomasz S. Mieszczanek Anne V. Jakobsen Elena Gardella Kern Olofsson Marina Nikanorova Allan Bayat Sebastian Ortiz Sarah Weckhuysen Cecilie Johannessen Landmark Orrin Devinsky Mary Chebib Philip K. Ahring Guido Rubboli Rikke S. Møller Epilepsia Abstract Objective The semisynthetic compound vinpocetine has gained attention as a potential precision medicine for developmental and epileptic encephalopathies caused by loss‐of‐function (LoF) variants in γ‐aminobutyric acid type A (GABA A ) receptor genes. As a positive allosteric modulator of GABA A receptors, case reports suggest that vinpocetine can reduce epileptiform activity and seizure frequency, while improving cognitive function in patients with GABA A receptor‐related epilepsies. Here, we extend these observations with a retrospective observational study evaluating the response to vinpocetine in an additional seven patients. Methods Patients initiated treatment with vinpocetine between 2018 and 2025 at the Danish Epilepsy Centre or abroad. Clinical data were collected from medical records, seizure diaries, and neuropsychological assessments. The modulatory efficacy of vinpocetine was investigated using electrophysiological studies. Results Nine patients harboring eight GABA A receptor LoF variants were given add‐on vinpocetine treatment. Electrophysiological analyses confirmed dose‐dependent positive modulation by vinpocetine across tested variants. Six patients with a median age of 15.5 years (range = 6–29) continued treatment for a median of 24 months (range = 12–90), whereas three discontinued due to adverse effects (AEs) or lack of efficacy. The patients' level of function ranged from normal to moderate intellectual disability, psychiatric comorbidities, and behavioral disturbances. Four patients initiated vinpocetine due to uncontrolled seizures. One became seizure‐free, and two experienced a 50%–55% reduction. Electroencephalograms demonstrated improved spike–wave indexes in four patients. Six showed improvement in nonseizure factors, and caregivers reported reduced aggressivity and better vocabulary in one. Vinpocetine was well tolerated, with only mild and reversible AEs reported. Significance Adjunctive vinpocetine shows promise as a targeted therapy for patients with GABA A receptor LoF variants, decreasing seizure frequency and positively impacting nonseizure factors, with only mild AEs reported. Vinpocetine may be a safe and effective therapy for patients with GABA A receptor‐related epilepsies, which should be investigated further in future N ‐of‐1 trials. 10.1002/epi.70310 http://creativecommons.org/licenses/by/4.0/ |
| doi_str_mv | 10.1002/epi.70310 |
| format | Artículo Open Access |
| id | wiley_oa_10_1002_epi_70310 |
| institution | Wiley Open Access |
| license_str_mv | http://creativecommons.org/licenses/by/4.0/ |
| publishDate | 2026 |
| publisher | Wiley |
| record_format | wiley_oa |
| spellingShingle | Add‐on treatment with vinpocetine reduces seizure frequency and improves comorbidities in patients with loss‐of‐function γ‐aminobutyric acid type A receptor variants Cathrine E. Gjerulfsen Vivian W. Y. Liao Tomasz S. Mieszczanek Anne V. Jakobsen Elena Gardella Kern Olofsson Marina Nikanorova Allan Bayat Sebastian Ortiz Sarah Weckhuysen Cecilie Johannessen Landmark Orrin Devinsky Mary Chebib Philip K. Ahring Guido Rubboli Rikke S. Møller Epilepsia Add‐on treatment with vinpocetine reduces seizure frequency and improves comorbidities in patients with loss‐of‐function γ‐aminobutyric acid type A receptor variants Cathrine E. Gjerulfsen Vivian W. Y. Liao Tomasz S. Mieszczanek Anne V. Jakobsen Elena Gardella Kern Olofsson Marina Nikanorova Allan Bayat Sebastian Ortiz Sarah Weckhuysen Cecilie Johannessen Landmark Orrin Devinsky Mary Chebib Philip K. Ahring Guido Rubboli Rikke S. Møller Epilepsia Abstract Objective The semisynthetic compound vinpocetine has gained attention as a potential precision medicine for developmental and epileptic encephalopathies caused by loss‐of‐function (LoF) variants in γ‐aminobutyric acid type A (GABA A ) receptor genes. As a positive allosteric modulator of GABA A receptors, case reports suggest that vinpocetine can reduce epileptiform activity and seizure frequency, while improving cognitive function in patients with GABA A receptor‐related epilepsies. Here, we extend these observations with a retrospective observational study evaluating the response to vinpocetine in an additional seven patients. Methods Patients initiated treatment with vinpocetine between 2018 and 2025 at the Danish Epilepsy Centre or abroad. Clinical data were collected from medical records, seizure diaries, and neuropsychological assessments. The modulatory efficacy of vinpocetine was investigated using electrophysiological studies. Results Nine patients harboring eight GABA A receptor LoF variants were given add‐on vinpocetine treatment. Electrophysiological analyses confirmed dose‐dependent positive modulation by vinpocetine across tested variants. Six patients with a median age of 15.5 years (range = 6–29) continued treatment for a median of 24 months (range = 12–90), whereas three discontinued due to adverse effects (AEs) or lack of efficacy. The patients' level of function ranged from normal to moderate intellectual disability, psychiatric comorbidities, and behavioral disturbances. Four patients initiated vinpocetine due to uncontrolled seizures. One became seizure‐free, and two experienced a 50%–55% reduction. Electroencephalograms demonstrated improved spike–wave indexes in four patients. Six showed improvement in nonseizure factors, and caregivers reported reduced aggressivity and better vocabulary in one. Vinpocetine was well tolerated, with only mild and reversible AEs reported. Significance Adjunctive vinpocetine shows promise as a targeted therapy for patients with GABA A receptor LoF variants, decreasing seizure frequency and positively impacting nonseizure factors, with only mild AEs reported. Vinpocetine may be a safe and effective therapy for patients with GABA A receptor‐related epilepsies, which should be investigated further in future N ‐of‐1 trials. 10.1002/epi.70310 http://creativecommons.org/licenses/by/4.0/ |
| title | Add‐on treatment with vinpocetine reduces seizure frequency and improves comorbidities in patients with loss‐of‐function γ‐aminobutyric acid type A receptor variants |
| topic | Epilepsia |
| url | https://onlinelibrary.wiley.com/doi/10.1002/epi.70310 |