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<article article-type="research-article" dtd-version="1.3" xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" xml:lang="en"><front><journal-meta><journal-id journal-id-type="publisher-id">ppan</journal-id><journal-title-group><journal-title xml:lang="en">Personalized Psychiatry and Neurology</journal-title><trans-title-group xml:lang="ru"><trans-title>Personalized Psychiatry and Neurology</trans-title></trans-title-group></journal-title-group><issn pub-type="epub">2712-9179</issn><publisher><publisher-name>V. M. Bekhterev National Medical Research Centre for Psychiatry and Neurology of the Ministry of Health of the Russian Federation (Bekhterev NMRC PN)</publisher-name></publisher></journal-meta><article-meta><article-id pub-id-type="doi">10.52667/2712-9179-2026-6-2-46-55</article-id><article-id custom-type="elpub" pub-id-type="custom">ppan-179</article-id><article-categories><subj-group subj-group-type="heading"><subject>Research Article</subject></subj-group><subj-group subj-group-type="section-heading" xml:lang="en"><subject>ARTICLE</subject></subj-group></article-categories><title-group><article-title>Pharmacogenetically Guided Pharmacotherapy for Alcohol Withdrawal Syndrome Complicated by Seizures: A Pilot Randomized Controlled Trial</article-title><trans-title-group xml:lang="ru"><trans-title></trans-title></trans-title-group></title-group><contrib-group><contrib contrib-type="author" corresp="yes"><name-alternatives><name name-style="western" xml:lang="en"><surname>Skryabin</surname><given-names>Valentin Yu.</given-names></name></name-alternatives><bio xml:lang="en"><p>Moscow 109390</p></bio><email xlink:type="simple">sardonios@yandex.ru</email><xref ref-type="aff" rid="aff-1"/></contrib><contrib contrib-type="author" corresp="yes"><name-alternatives><name name-style="western" xml:lang="en"><surname>Sokolova</surname><given-names>Svetlana I.</given-names></name></name-alternatives><bio xml:lang="en"><p>Moscow 109390</p></bio><xref ref-type="aff" rid="aff-1"/></contrib><contrib contrib-type="author" corresp="yes"><name-alternatives><name name-style="western" xml:lang="en"><surname>Ivanchenko</surname><given-names>Valentina A.</given-names></name></name-alternatives><bio xml:lang="en"><p>Moscow 109390</p></bio><xref ref-type="aff" rid="aff-1"/></contrib><contrib contrib-type="author" corresp="yes"><name-alternatives><name name-style="western" xml:lang="en"><surname>Matskevich</surname><given-names>Alla A.</given-names></name></name-alternatives><bio xml:lang="en"><p>Moscow 109390</p></bio><xref ref-type="aff" rid="aff-1"/></contrib><contrib contrib-type="author" corresp="yes"><name-alternatives><name name-style="western" xml:lang="en"><surname>Masyakin</surname><given-names>Anton V.</given-names></name></name-alternatives><bio xml:lang="en"><p>Moscow 109390</p></bio><xref ref-type="aff" rid="aff-1"/></contrib></contrib-group><aff xml:lang="en" id="aff-1"><institution>Moscow Research and Practical Centre on Addictions</institution><country>Russian Federation</country></aff><pub-date pub-type="collection"><year>2026</year></pub-date><pub-date pub-type="epub"><day>24</day><month>06</month><year>2026</year></pub-date><volume>6</volume><issue>2</issue><fpage>46</fpage><lpage>55</lpage><permissions><copyright-statement>Copyright &amp;#x00A9; Skryabin V.Y., Sokolova S.I., Ivanchenko V.A., Matskevich A.A., Masyakin A.V., 2026</copyright-statement><copyright-year>2026</copyright-year><copyright-holder xml:lang="ru">Skryabin V.Y., Sokolova S.I., Ivanchenko V.A., Matskevich A.A., Masyakin A.V.</copyright-holder><copyright-holder xml:lang="en">Skryabin V.Y., Sokolova S.I., Ivanchenko V.A., Matskevich A.A., Masyakin A.V.</copyright-holder><license xml:lang="ru" license-type="creative-commons-attribution" xlink:href="https://creativecommons.org/licenses/by/4.0/" xlink:type="simple"><license-p>Данная работа распространяется под лицензией Creative Commons Attribution 4.0.</license-p></license><license xml:lang="en" license-type="creative-commons-attribution" xlink:href="https://creativecommons.org/licenses/by/4.0/" xlink:type="simple"><license-p>This work is licensed under a Creative Commons Attribution 4.0 License.</license-p></license></permissions><self-uri xlink:href="https://www.jppn.ru/jour/article/view/179">https://www.jppn.ru/jour/article/view/179</self-uri><abstract><p>Alcohol withdrawal syndrome (AWS) complicated by seizures requires rapid symptom control while avoiding excessive sedation and other dose-related adverse drug reactions. This pilot randomized controlled trial evaluated whether pharmacogenetically guided optimization of pharmacotherapy could improve early clinical dynamics and tolerability in this high-risk inpatient population. Fifty inpatients with alcohol withdrawal state with convulsions (ICD-10 F10.31) were randomized 1:1 to pharmacogenetically guided treatment or control care. Pharmacogenetic testing was performed at admission in all patients; treating physicians in the intervention group received the true PGx report, whereas control physicians received a neutral report of identical format indicating wild-type genotypes and standard dosing. The primary endpoint was the area under the CIWA-Ar curve over 72 hours. Mean AUC CIWA-Ar was lower in the pharmacogenetic group than in controls (790 ± 175 vs 905 ± 185 score-hours; p = 0.032), with consistent non-parametric sensitivity analysis. Repeated-measures modelling showed a significant group-by-time interaction, with adjusted differences at 48 and 72 hours. The pharmacogenetic group also showed shorter time to stabilization, lower rescue medication burden, shorter hospitalization, lower UKU scores, and fewer clinically significant adverse events. These preliminary findings suggest that pharmacogenetically guided prescribing may improve tolerability and early withdrawal dynamics, but require confirmation in larger multicentre studies.</p></abstract><kwd-group xml:lang="en"><kwd>alcohol withdrawal syndrome</kwd><kwd>withdrawal seizures</kwd><kwd>pharmacogenetics</kwd><kwd>CYP2C19</kwd><kwd>CYP2D6</kwd><kwd>CIWA-Ar</kwd><kwd>UKU</kwd><kwd>personalized medicine.</kwd></kwd-group></article-meta></front><back><ref-list><title>References</title><ref id="cit1"><label>1</label><citation-alternatives><mixed-citation xml:lang="ru">Schuckit M.A. Recognition and management of withdrawal delirium (delirium tremens). N. Engl. J. Med. 2014; 371: 2109–2113. https://doi.org/10.1056/NEJMra1407298.</mixed-citation><mixed-citation xml:lang="en">Schuckit M.A. Recognition and management of withdrawal delirium (delirium tremens). N. Engl. J. Med. 2014; 371: 2109–2113. https://doi.org/10.1056/NEJMra1407298.</mixed-citation></citation-alternatives></ref><ref id="cit2"><label>2</label><citation-alternatives><mixed-citation xml:lang="ru">Kádár B.K., Gajdics J., Pribék I.K., et al. Characterization of alcohol-related seizures in withdrawal syndrome. Epilepsia Open 2024; 9: 679–688. https://doi.org/10.1002/epi4.12906.</mixed-citation><mixed-citation xml:lang="en">Kádár B.K., Gajdics J., Pribék I.K., et al. Characterization of alcohol-related seizures in withdrawal syndrome. Epilepsia Open 2024; 9: 679–688. https://doi.org/10.1002/epi4.12906.</mixed-citation></citation-alternatives></ref><ref id="cit3"><label>3</label><citation-alternatives><mixed-citation xml:lang="ru">The ASAM Clinical Practice Guideline on Alcohol Withdrawal Management. J. Addict. Med. 2020; 14: 1–72. https://doi.org/10.1097/ADM.0000000000000668.</mixed-citation><mixed-citation xml:lang="en">The ASAM Clinical Practice Guideline on Alcohol Withdrawal Management. J. Addict. Med. 2020; 14: 1–72. https://doi.org/10.1097/ADM.0000000000000668.</mixed-citation></citation-alternatives></ref><ref id="cit4"><label>4</label><citation-alternatives><mixed-citation xml:lang="ru">Sullivan J.T., Sykora K., Schneiderman J., et al. Assessment of alcohol withdrawal: The revised Clinical Institute Withdrawal Assessment for Alcohol scale (CIWA-Ar). Br. J. Addict. 1989; 84: 1353–1357. https://doi.org/10.1111/j.1360-0443.1989.tb00737.x.</mixed-citation><mixed-citation xml:lang="en">Sullivan J.T., Sykora K., Schneiderman J., et al. Assessment of alcohol withdrawal: The revised Clinical Institute Withdrawal Assessment for Alcohol scale (CIWA-Ar). Br. J. Addict. 1989; 84: 1353–1357. https://doi.org/10.1111/j.1360-0443.1989.tb00737.x.</mixed-citation></citation-alternatives></ref><ref id="cit5"><label>5</label><citation-alternatives><mixed-citation xml:lang="ru">Amato L., Minozzi S., Vecchi S. Davoli, M. Benzodiazepines for alcohol withdrawal. Cochrane Database Syst. Rev. 2010; 2010: CD005063. https://doi.org/10.1002/14651858.CD005063.pub3.</mixed-citation><mixed-citation xml:lang="en">Amato L., Minozzi S., Vecchi S. Davoli, M. Benzodiazepines for alcohol withdrawal. Cochrane Database Syst. Rev. 2010; 2010: CD005063. https://doi.org/10.1002/14651858.CD005063.pub3.</mixed-citation></citation-alternatives></ref><ref id="cit6"><label>6</label><citation-alternatives><mixed-citation xml:lang="ru">Barrons R., Roberts N. The role of carbamazepine and oxcarbazepine in alcohol withdrawal syndrome. J. Clin. Pharm. Ther. 2010; 35: 153–167. https://doi.org/10.1111/j.1365-2710.2009.01098.x.</mixed-citation><mixed-citation xml:lang="en">Barrons R., Roberts N. The role of carbamazepine and oxcarbazepine in alcohol withdrawal syndrome. J. Clin. Pharm. Ther. 2010; 35: 153–167. https://doi.org/10.1111/j.1365-2710.2009.01098.x.</mixed-citation></citation-alternatives></ref><ref id="cit7"><label>7</label><citation-alternatives><mixed-citation xml:lang="ru">Eyer F., Schreckenberg M., Hecht D., et al. Carbamazepine and valproate as adjuncts in the treatment of alcohol withdrawal syndrome: A retrospective cohort study. Alcohol Alcohol. 2011; 46: 177–184. https://doi.org/10.1093/alcalc/agr005.</mixed-citation><mixed-citation xml:lang="en">Eyer F., Schreckenberg M., Hecht D., et al. Carbamazepine and valproate as adjuncts in the treatment of alcohol withdrawal syndrome: A retrospective cohort study. Alcohol Alcohol. 2011; 46: 177–184. https://doi.org/10.1093/alcalc/agr005.</mixed-citation></citation-alternatives></ref><ref id="cit8"><label>8</label><citation-alternatives><mixed-citation xml:lang="ru">Bousman C.A., Al Maruf A., Ferri Marques D., et al. The emergence, implementation, and future growth of phar-macogenomics in psychiatry: A narrative review. Psychol. Med. 2023: 53: 7983–7993. https://doi.org/10.1017/S0033291723002817.</mixed-citation><mixed-citation xml:lang="en">Bousman C.A., Al Maruf A., Ferri Marques D., et al. The emergence, implementation, and future growth of phar-macogenomics in psychiatry: A narrative review. Psychol. Med. 2023: 53: 7983–7993. https://doi.org/10.1017/S0033291723002817.</mixed-citation></citation-alternatives></ref><ref id="cit9"><label>9</label><citation-alternatives><mixed-citation xml:lang="ru">Bousman C.A., Stevenson, J.M.; Ramsey, L.B.; et al. Clinical Pharmacogenetics Implementation Consortium (CPIC) guideline for CYP2D6, CYP2C19, CYP2B6, SLC6A4, and HTR2A genotypes and serotonin reuptake inhibitor antidepressants. Clin. Pharmacol. Ther. 2023; 114: 51–68. https://doi.org/10.1002/cpt.2903.</mixed-citation><mixed-citation xml:lang="en">Bousman C.A., Stevenson, J.M.; Ramsey, L.B.; et al. Clinical Pharmacogenetics Implementation Consortium (CPIC) guideline for CYP2D6, CYP2C19, CYP2B6, SLC6A4, and HTR2A genotypes and serotonin reuptake inhibitor antidepressants. Clin. Pharmacol. Ther. 2023; 114: 51–68. https://doi.org/10.1002/cpt.2903.</mixed-citation></citation-alternatives></ref><ref id="cit10"><label>10</label><citation-alternatives><mixed-citation xml:lang="ru">Ho T.T., Noble M.,Tran B.A., et al. Clinical impact of the CYP2C19 gene on diazepam for the management of alcohol with-drawal syndrome. J. Pers. Med. 2023; 13: 285. https://doi.org/10.3390/jpm13020285.</mixed-citation><mixed-citation xml:lang="en">Ho T.T., Noble M.,Tran B.A., et al. Clinical impact of the CYP2C19 gene on diazepam for the management of alcohol with-drawal syndrome. J. Pers. Med. 2023; 13: 285. https://doi.org/10.3390/jpm13020285.</mixed-citation></citation-alternatives></ref><ref id="cit11"><label>11</label><citation-alternatives><mixed-citation xml:lang="ru">Skryabin V., Masyakin A., Pozdniakov S., et al. Optimizing antipsychotic therapy in acute alcoholic hallucinosis through pharmacogenetic testing. Addicta Turk. J. Addict. 2024; 11: 374–377. https://doi.org/10.5152/ADDICTA.2024.24224.</mixed-citation><mixed-citation xml:lang="en">Skryabin V., Masyakin A., Pozdniakov S., et al. Optimizing antipsychotic therapy in acute alcoholic hallucinosis through pharmacogenetic testing. Addicta Turk. J. Addict. 2024; 11: 374–377. https://doi.org/10.5152/ADDICTA.2024.24224.</mixed-citation></citation-alternatives></ref><ref id="cit12"><label>12</label><citation-alternatives><mixed-citation xml:lang="ru">Lingjærde O., Ahlfors U.G., Bech P., et al. The UKU side effect rating scale: A new comprehensive rating scale for psycho-tropic drugs and a cross-sectional study of side effects in neuroleptic-treated patients. Acta Psychiatr. Scand. Suppl. 1987; 334: 1–100. https://doi.org/10.1111/j.1600-0447.1987.tb10566.x.</mixed-citation><mixed-citation xml:lang="en">Lingjærde O., Ahlfors U.G., Bech P., et al. The UKU side effect rating scale: A new comprehensive rating scale for psycho-tropic drugs and a cross-sectional study of side effects in neuroleptic-treated patients. Acta Psychiatr. Scand. Suppl. 1987; 334: 1–100. https://doi.org/10.1111/j.1600-0447.1987.tb10566.x.</mixed-citation></citation-alternatives></ref><ref id="cit13"><label>13</label><citation-alternatives><mixed-citation xml:lang="ru">Holleck J.L., Merchant N., Gunderson C.G. Symptom-triggered therapy for alcohol withdrawal syndrome: A systematic review and meta-analysis of randomized controlled trials. J. Gen. Intern. Med. 2019; 34: 1018–1024. https://doi.org/10.1007/s11606-019-04899-7.</mixed-citation><mixed-citation xml:lang="en">Holleck J.L., Merchant N., Gunderson C.G. Symptom-triggered therapy for alcohol withdrawal syndrome: A systematic review and meta-analysis of randomized controlled trials. J. Gen. Intern. Med. 2019; 34: 1018–1024. https://doi.org/10.1007/s11606-019-04899-7.</mixed-citation></citation-alternatives></ref><ref id="cit14"><label>14</label><citation-alternatives><mixed-citation xml:lang="ru">Mayo-Smith M.F., Beecher L.H., Fischer T.L.; et al. Management of alcohol withdrawal delirium: An evidence-based practice guideline. Arch. Intern. Med. 2004; 164: 1405–1412. https://doi.org/10.1001/archinte.164.13.1405.</mixed-citation><mixed-citation xml:lang="en">Mayo-Smith M.F., Beecher L.H., Fischer T.L.; et al. Management of alcohol withdrawal delirium: An evidence-based practice guideline. Arch. Intern. Med. 2004; 164: 1405–1412. https://doi.org/10.1001/archinte.164.13.1405.</mixed-citation></citation-alternatives></ref><ref id="cit15"><label>15</label><citation-alternatives><mixed-citation xml:lang="ru">Benjamini Y., Hochberg Y. Controlling the false discovery rate: A practical and powerful approach to multiple testing. J. R. Stat. Soc. B 1995; 57: 289–300.</mixed-citation><mixed-citation xml:lang="en">Benjamini Y., Hochberg Y. Controlling the false discovery rate: A practical and powerful approach to multiple testing. J. R. Stat. Soc. B 1995; 57: 289–300.</mixed-citation></citation-alternatives></ref></ref-list><fn-group><fn fn-type="conflict"><p>The authors declare that there are no conflicts of interest present.</p></fn></fn-group></back></article>
