{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,4]],"date-time":"2026-06-04T10:31:50Z","timestamp":1780569110836,"version":"3.54.1"},"reference-count":74,"publisher":"Cambridge University Press (CUP)","issue":"5","license":[{"start":{"date-parts":[[2016,9,30]],"date-time":"2016-09-30T00:00:00Z","timestamp":1475193600000},"content-version":"unspecified","delay-in-days":0,"URL":"https:\/\/www.cambridge.org\/core\/terms"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["CNS Spectr."],"published-print":{"date-parts":[[2016,10]]},"abstract":"<jats:sec id=\"S1092852916000523_abs1\" sec-type=\"objectives\"><jats:title>Objectives<\/jats:title><jats:p>To meta-analytically summarize lamotrigine\u2019s effectiveness and safety in unipolar and bipolar depression.<\/jats:p><\/jats:sec><jats:sec id=\"S1092852916000523_abs2\" sec-type=\"methods\"><jats:title>Methods<\/jats:title><jats:p>We conducted systematic PubMed and SCOPUS reviews (last search =10\/01\/2015) of randomized controlled trials comparing lamotrigine to placebo or other agents with antidepressant activity in unipolar or bipolar depression. We performed a random-effects meta-analysis of depression ratings, response, remission, and adverse effects calculating standardized mean difference (SMD) and risk ratio (RR) \u00b195% confidence intervals (CIs).<\/jats:p><\/jats:sec><jats:sec id=\"S1092852916000523_abs3\" sec-type=\"results\"><jats:title>Results<\/jats:title><jats:p>Eighteen studies (n=2152, duration=9.83 weeks) in patients with unipolar depression (studies=4, n=187; monotherapy vs lithium=1, augmentation of antidepressants vs placebo=3) or bipolar depression (studies=14, n=1965; monotherapy vs placebo=5, monotherapy vs lithium or olanzapine+fluoxetine=2, augmentation of antidepressants vs placebo=1, augmentation of mood stabilizers vs placebo=3, augmentation of mood stabilizers vs trancylpromine, citalopram, or inositol=3) were meta-analyzed. Lamotrigine\u2019s efficacy for depressive symptoms did not differ significantly in monotherapy vs augmentation studies (vs. placebo: p=0.98, I<jats:sup>2<\/jats:sup>=0%; vs active agents: p=0.48, I<jats:sup>2<\/jats:sup>=0%) or in unipolar vs bipolar patients (vs placebo: p=0.60, I<jats:sup>2<\/jats:sup>=0%), allowing pooling of each placebo-controlled and active-controlled trials. Lamotrigine outperformed placebo regarding depressive symptoms (studies=11, n=713 vs n=696; SMD=\u20130.15, 95% CI=\u20130.27, \u20130.02, p=0.02, heterogeneity: p=0.24) and response (after removing one extreme outlier; RR=1.42, 95% CI=1.13\u20131.78; p=0.003, heterogeneity: p=0.08). Conversely, lamotrigine did not differ regarding efficacy on depressive symptoms, response, or remission from lithium, olanzapine+fluoxetine, citalopram, or inositol (studies=6, n=306 vs n=318, p-values=0.85\u20130.92). Adverse effects and all-cause\/specific-cause discontinuation were similar across all comparisons.<\/jats:p><\/jats:sec><jats:sec id=\"S1092852916000523_abs4\" sec-type=\"conclusions\"><jats:title>Conclusions<\/jats:title><jats:p>Lamotrigine was superior to placebo in improving unipolar and bipolar depressive symptoms, without causing more frequent adverse effects\/discontinuations. Lamotrigine did not differ from lithium, olanzapine+fluoxetine, citalopram, or inositol.<\/jats:p><\/jats:sec>","DOI":"10.1017\/s1092852916000523","type":"journal-article","created":{"date-parts":[[2016,9,30]],"date-time":"2016-09-30T07:54:50Z","timestamp":1475222090000},"page":"403-418","source":"Crossref","is-referenced-by-count":63,"title":["Lamotrigine compared to placebo and other agents with antidepressant activity in patients with unipolar and bipolar depression: a comprehensive meta-analysis of efficacy and safety outcomes in short-term trials"],"prefix":"10.1017","volume":"21","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4877-7233","authenticated-orcid":false,"given":"Marco","family":"Solmi","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9328-289X","authenticated-orcid":false,"given":"Nicola","family":"Veronese","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leonardo","family":"Zaninotto","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marc L. 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