{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,12]],"date-time":"2025-10-12T20:15:11Z","timestamp":1760300111474},"reference-count":13,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"1","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2019,2]]},"abstract":"\n Background:<\/jats:title>\n In a previous study, the authors had shown that in treatment-resistant depressive disorder, an early therapeutic response to lamotrigine augmentation therapy is dependent on its plasma concentrations. Lamotrigine is mainly metabolized by UGT1A4 and UGT2B7, and polymorphisms of said UGTs<\/jats:italic> that affect enzyme activities have been reported. This study investigated the effect of these polymorphisms on the steady-state plasma concentrations (Css) of lamotrigine in patients with treatment-resistant depressive disorder receiving lamotrigine as augmentation therapy.<\/jats:p>\n <\/jats:sec>\n \n Methods:<\/jats:title>\n The subjects were 103 depressed patients who had already shown insufficient response to at least 3 psychotropics including antidepressants, mood stabilizers, and atypical antipsychotics. The diagnoses were major depressive disorder (n = 46), bipolar II disorder (n = 44), and bipolar I disorder (n = 13). They received augmentation therapy with lamotrigine for 8 weeks. The final doses of lamotrigine were 100 mg\/d for 67 subjects who were not taking valproate and 75 mg\/d for 36 subjects taking valproate, respectively. Blood sampling was performed at the 8th week. Plasma concentrations of lamotrigine were measured by high-performance liquid chromatography. The genotypes of UGT1A4<\/jats:italic> 142T>G, UGT2B7<\/jats:italic> -161C>T, and UGT2B7<\/jats:italic> 372A>G were identified by polymerase chain reaction analyses.<\/jats:p>\n <\/jats:sec>\n \n Results:<\/jats:title>\n There were no significant relationships between these polymorphisms and the Css of lamotrigine in the subjects regardless of valproate comedication.<\/jats:p>\n <\/jats:sec>\n \n Conclusions:<\/jats:title>\n This study suggests that these genetic polymorphisms do not affect the Css of lamotrigine in patients with treatment-resistant depressive disorder receiving lamotrigine as augmentation therapy.<\/jats:p>\n <\/jats:sec>","DOI":"10.1097\/ftd.0000000000000577","type":"journal-article","created":{"date-parts":[[2018,11,29]],"date-time":"2018-11-29T17:12:08Z","timestamp":1543511528000},"page":"86-90","source":"Crossref","is-referenced-by-count":18,"title":["Relationship Between UGT1A4 and UGT2B7 Polymorphisms and the Steady-State Plasma Concentrations of Lamotrigine in Patients With Treatment-Resistant Depressive Disorder Receiving Lamotrigine as Augmentation Therapy"],"prefix":"10.1097","volume":"41","author":[{"given":"Takeshi","family":"Suzuki","sequence":"first","affiliation":[{"name":"Hospital Pharmacy and"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kazuo","family":"Mihara","sequence":"additional","affiliation":[{"name":"Neuropsychiatry, Graduate School of Medicine, University of the Ryukyus, Nishihara, Okinawa, Japan."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Goyo","family":"Nagai","sequence":"additional","affiliation":[{"name":"Neuropsychiatry, Graduate School of Medicine, University of the Ryukyus, Nishihara, Okinawa, Japan."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shoko","family":"Kagawa","sequence":"additional","affiliation":[{"name":"Neuropsychiatry, Graduate School of Medicine, University of the Ryukyus, Nishihara, Okinawa, Japan."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Akifumi","family":"Nakamura","sequence":"additional","affiliation":[{"name":"Neuropsychiatry, Graduate School of Medicine, University of the Ryukyus, Nishihara, Okinawa, Japan."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kenji","family":"Nemoto","sequence":"additional","affiliation":[{"name":"Neuropsychiatry, Graduate School of Medicine, University of the Ryukyus, Nishihara, Okinawa, Japan."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tsuyoshi","family":"Kondo","sequence":"additional","affiliation":[{"name":"Neuropsychiatry, Graduate School of Medicine, University of the Ryukyus, Nishihara, Okinawa, Japan."}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"276","reference":[{"key":"R1-20230814","doi-asserted-by":"crossref","first-page":"4","DOI":"10.1192\/bjp.bp.107.048504","article-title":"Lamotrigine for treatment of bipolar depression: independent 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use of lamotrigine","volume":"18","author":"Reimers","year":"2009","journal-title":"Pharmacoepidemiol Drug Saf."},{"key":"R9-20230814","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.eplepsyres.2011.01.016","article-title":"The relationship between UGT1A4 polymorphism and serum concentration of lamotrigine in patients with epilepsy","volume":"95","author":"Gulcebi","year":"2011","journal-title":"Epilepsy Res."},{"key":"R10-20230814","doi-asserted-by":"crossref","first-page":"941","DOI":"10.1007\/s00228-014-1690-1","article-title":"Correlation of the UGT1A4 gene polymorphism with serum concentration and therapeutic efficacy of lamotrigine in Han Chinese of Northern China","volume":"70","author":"Chang","year":"2014","journal-title":"Eur J Clin Pharmacol."},{"key":"R11-20230814","doi-asserted-by":"crossref","first-page":"1285","DOI":"10.1007\/s00228-012-1449-5","article-title":"Influence of the UGT2B7 -161C>T polymorphism on the population pharmacokinetics of lamotrigine in Thai patients","volume":"69","author":"Singkham","year":"2013","journal-title":"Eur J Clin Pharmacol."},{"key":"R12-20230814","doi-asserted-by":"crossref","first-page":"177","DOI":"10.1097\/FTD.0b013e3181ceecc6","article-title":"UGT2B7 -161C>T polymorphism is associated with lamotrigine concentration-to-dose ratio in a multivariate study","volume":"32","author":"Blanca S\u00e1nchez","year":"2010","journal-title":"Ther Drug Monit."},{"key":"R13-20230814","doi-asserted-by":"crossref","first-page":"399","DOI":"10.1111\/bcp.12984","article-title":"Pharmacokinetics of lamotrigine and its metabolite N-2-glucuronide: influence of polymorphism of UDP-glucuronosyltransferases and drug transporters","volume":"82","author":"Milosheska","year":"2016","journal-title":"Br J Clin Pharmacol."},{"key":"R15-20230814","doi-asserted-by":"crossref","first-page":"693","DOI":"10.1111\/j.1365-2710.2012.01351.x","article-title":"Impact of age, weight and concomitant treatment on lamotrigine 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