{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T15:50:36Z","timestamp":1791474636399,"version":"4.3.4"},"reference-count":25,"publisher":"Oxford University Press (OUP)","issue":"2","license":[{"start":{"date-parts":[[2023,12,7]],"date-time":"2023-12-07T00:00:00Z","timestamp":1701907200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"DOI":"10.13039\/100008457","name":"University of Virginia","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100008457","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2024,1,17]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Topiramate (TPM), a GABA\/glutamate modulator, has shown positive results for treating alcohol use disorder (AUD), but causes significant cognitive adverse effects. TPM causes cognitive side effects by reducing glutathione levels in the frontal lobe. N-acetyl cysteine (NAC) increases level of intracellular glutathione. We hypothesized that combining NAC with TPM may mitigate the possible cognitive side effects of TPM, as well as working synergistically in reducing alcohol consumption more efficaciously than using TPM alone. A 12-week, double-blind randomized trial assessing the effects of combining NAC (1200\u00a0mg\/day) with TPM (200\u00a0mg\/day) vs TPM alone (i) cognitive side effects caused by TPM, (ii) percentage of heavy drinking days (PHDD) and percentage of days abstinent (PDA) using weekly calendar, and (iii) craving outcomes using the obsessive\u2013compulsive drinking scale. Seventeen participants were randomized into the study (nine received TPM\u2009+\u2009NAC and eight matching TPM\u2009+\u2009Placebo). Cognitive adverse events were not significantly different between the treatment arms (P\u2009=\u20090.581). There was no difference in PHDD (P\u2009=\u20090.536) and in PDA over the entire study period (P\u2009=\u20090.892). However, both treatment groups at study end, compared with the baseline, significantly reduced their PHDD and increased their PDA. As for cravings: TPM\u2009+\u2009NAC group has shown higher level in automaticity of drinking (P\u2009=\u20090.029) and interference due to drinking (P\u2009=\u20090.014) subscales compared with the TPM\u2009+\u2009Placebo group. No difference was observed between groups in terms of Drinking Obsessions and Alcohol Consumption subscales. This pilot study indicates that combining NAC with TPM is overall safe, but the addition of NAC has no significant benefit over placebo in the incidence of TPM-related cognitive impairment, and alcohol drinking. Furthermore, craving outcomes may become worse with the addition of NAC.<\/jats:p>","DOI":"10.1093\/alcalc\/agad082","type":"journal-article","created":{"date-parts":[[2023,12,9]],"date-time":"2023-12-09T09:42:15Z","timestamp":1702114935000},"source":"Crossref","is-referenced-by-count":3,"title":["Safety and tolerability of topiramate and N-acetyl cysteine combination in individuals with alcohol use disorder: a 12 week, randomized, double-blind, pilot study"],"prefix":"10.1093","volume":"59","author":[{"given":"Nassima A-D","family":"Tiouririne","sequence":"first","affiliation":[{"name":"Department of Psychiatry & Neurobehavioral Sciences, University of Virginia School of Medicine , 1300 Jefferson Park Ave. 22903 Charlottesville, VA , United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tevfik","family":"Kalelioglu","sequence":"additional","affiliation":[{"name":"Department of Psychiatry & Neurobehavioral Sciences, University of Virginia School of Medicine , 1300 Jefferson Park Ave. 22903 Charlottesville, VA , United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chamindi","family":"Seneviratne","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, University of Maryland School of Medicine , 670 West Baltimore St, 21201 Baltimore, MD , United States"},{"name":"Institute for Genome Sciences, University of Maryland School of Medicine , Health Sciences Facility III, 670 West Baltimore St, 21201 Baltimore, MD , United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xin-Qun","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Public Health Sciences, University of Virginia School of Medicine , 200 Jeanette Lancaster Way 22903 Charlottesville, VA , United States"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2023,12,7]]},"reference":[{"key":"2024011803333965800_ref1","doi-asserted-by":"crossref","first-page":"2103","DOI":"10.2174\/138161210791516404","article-title":"Topiramate in the new generation of drugs: efficacy in the treatment of alcoholic patients","volume":"16","author":"A. 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