{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T13:03:08Z","timestamp":1792069388196,"version":"4.4.0"},"reference-count":26,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2012,2,13]],"date-time":"2012-02-13T00:00:00Z","timestamp":1329091200000},"content-version":"vor","delay-in-days":12,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Bipolar Disorders"],"published-print":{"date-parts":[[2012,2]]},"abstract":"<jats:p>Anand A, Gunn AD, Barkay G, Karne HS, Nurnberger JI, Mathew SJ, Ghosh S. Early antidepressant effect of memantine during augmentation of lamotrigine inadequate response in bipolar depression: a double\u2010blind, randomized, placebo\u2010controlled trial. \u2028Bipolar Disord 2012: 14: 64\u201370. \u00a9 2012 The Authors. \u2028Journal compilation \u00a9 2012 John Wiley &amp; Sons A\/S.<\/jats:p><jats:p><jats:bold>Background:\u2002<\/jats:bold> Recent studies indicate that modulation of glutamate neurotransmission is associated with antidepressant response. Lamotrigine, an anticonvulsant which decreases presynaptic glutamate release, has been shown to be effective in the depressive phase of bipolar disorder (BD\u2010D); however, only 40\u201350% of patients have a full response. This pilot study investigated whether memantine, a low\u2010affinity N\u2010methyl\u2010D\u2010aspartate (NMDA) receptor antagonist approved for Alzheimer\u2019s disease, can augment the effects of lamotrigine.<\/jats:p><jats:p><jats:bold>Methods:\u2002<\/jats:bold> BD\u2010D outpatients in a major depressive episode on a stable dose of lamotrigine (100\u2003mg or more) were randomized to either memantine (starting dose of 5\u2003mg increased up to 20\u2003mg over four\u2003weeks, then 20\u2003mg stable dose from four to eight\u2003weeks) or matching pill placebo for eight\u2003weeks. Patients were rated on the 17\u2010item Hamilton Depression Rating Scale (HDRS) and other behavioral measures weekly.<\/jats:p><jats:p><jats:bold>Results:\u2002<\/jats:bold> The eight\u2010week repeated\u2010measures mixed\u2010effect model for HDRS was not significant for memantine (n\u2003=\u200314) versus placebo (n\u2003=\u200315). Exploratory mixed\u2010effect analyses for the first four\u2003weeks, while the memantine dose was being titrated up every week, revealed a significant decrease in HDRS scores from baseline (p\u2003=\u20030.007).<\/jats:p><jats:p><jats:bold>Conclusion:\u2002<\/jats:bold> This proof\u2010of\u2010concept study failed to show a statistically significant benefit of memantine augmentation of lamotrigine for patients with BD\u2010D over eight\u2003weeks. However, memantine had an antidepressant effect early on in the treatment while its dose was being titrated up. Larger placebo\u2010controlled studies are needed to ascertain optimal timing and dosing for memantine augmentation of lamotrigine in BD\u2010D.<\/jats:p>","DOI":"10.1111\/j.1399-5618.2011.00971.x","type":"journal-article","created":{"date-parts":[[2012,2,13]],"date-time":"2012-02-13T15:24:42Z","timestamp":1329146682000},"page":"64-70","source":"Crossref","is-referenced-by-count":57,"title":["Early antidepressant effect of memantine during augmentation of lamotrigine inadequate response in bipolar depression: a double\u2010blind, randomized, placebo\u2010controlled trial"],"prefix":"10.1111","volume":"14","author":[{"given":"Amit","family":"Anand","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Abigail D","family":"Gunn","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gavriel","family":"Barkay","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Harish S","family":"Karne","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John I","family":"Nurnberger","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sanjay J","family":"Mathew","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Samiran","family":"Ghosh","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2012,2,13]]},"reference":[{"key":"e_1_2_7_2_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.pharmtox.011008.145533"},{"key":"e_1_2_7_3_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrd2462"},{"key":"e_1_2_7_4_2","doi-asserted-by":"publisher","DOI":"10.1038\/nm1210-1384"},{"key":"e_1_2_7_5_2","doi-asserted-by":"publisher","DOI":"10.1001\/archgenpsychiatry.2010.138"},{"key":"e_1_2_7_6_2","doi-asserted-by":"publisher","DOI":"10.1016\/0014-2999(90)90204-J"},{"key":"e_1_2_7_7_2","doi-asserted-by":"publisher","DOI":"10.4088\/JCP.v60n0203"},{"key":"e_1_2_7_8_2","doi-asserted-by":"publisher","DOI":"10.1001\/archpsyc.57.3.270"},{"key":"e_1_2_7_9_2","doi-asserted-by":"publisher","DOI":"10.1001\/archpsyc.1994.03950030035004"},{"key":"e_1_2_7_10_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0006-3223(99)00230-9"},{"key":"e_1_2_7_11_2","doi-asserted-by":"publisher","DOI":"10.1001\/archgenpsychiatry.2010.90"},{"key":"e_1_2_7_12_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopsych.2009.04.029"},{"key":"e_1_2_7_13_2","doi-asserted-by":"publisher","DOI":"10.1001\/archpsyc.63.8.856"},{"key":"e_1_2_7_14_2","doi-asserted-by":"publisher","DOI":"10.2165\/00023210-200822090-00004"},{"key":"e_1_2_7_15_2","doi-asserted-by":"publisher","DOI":"10.1176\/appi.ajp.161.1.171"},{"key":"e_1_2_7_16_2","doi-asserted-by":"publisher","DOI":"10.1176\/appi.ajp.161.11.2132"},{"key":"e_1_2_7_17_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopsych.2004.11.023"},{"key":"e_1_2_7_18_2","doi-asserted-by":"publisher","DOI":"10.1017\/S1461145709000169"},{"key":"e_1_2_7_19_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.coph.2005.09.007"},{"key":"e_1_2_7_20_2","doi-asserted-by":"publisher","DOI":"10.1176\/appi.ajp.163.1.153"},{"key":"e_1_2_7_21_2","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.17-08-02921.1997"},{"key":"e_1_2_7_22_2","first-page":"1940","article-title":"Concurrent downregulation of a glutamate transporter and receptor in glaucoma","volume":"41","author":"Naskar R","year":"2000","journal-title":"Invest Ophthalmol Vis Sci"},{"key":"e_1_2_7_23_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.euroneuro.2006.01.003"},{"key":"e_1_2_7_24_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.2044-8341.1959.tb00467.x"},{"key":"e_1_2_7_25_2","doi-asserted-by":"publisher","DOI":"10.1192\/bjp.133.5.429"},{"key":"e_1_2_7_26_2","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2009.1943"},{"key":"e_1_2_7_27_2","doi-asserted-by":"publisher","DOI":"10.1034\/j.1399-5618.2000.020107.x"}],"container-title":["Bipolar Disorders"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2Fj.1399-5618.2011.00971.x","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/j.1399-5618.2011.00971.x","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,31]],"date-time":"2023-10-31T15:41:55Z","timestamp":1698766915000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/j.1399-5618.2011.00971.x"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2012,2]]},"references-count":26,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2012,2]]}},"alternative-id":["10.1111\/j.1399-5618.2011.00971.x"],"URL":"https:\/\/doi.org\/10.1111\/j.1399-5618.2011.00971.x","archive":["Portico"],"relation":{},"ISSN":["1398-5647","1399-5618"],"issn-type":[{"value":"1398-5647","type":"print"},{"value":"1399-5618","type":"electronic"}],"subject":[],"published":{"date-parts":[[2012,2]]}}}