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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

  • Marco Solmi (a1) (a2), Nicola Veronese (a2) (a3), Leonardo Zaninotto (a2) (a4), Marc L. M. van der Loos (a5), Keming Gao (a6), Ayal Schaffer (a7), Catherine Reis (a7), Claus Normann (a8), Ion-George Anghelescu (a9) and Christoph U. Correll (a2) (a10) (a11) (a12) (a13)...



To meta-analytically summarize lamotrigine’s effectiveness and safety in unipolar and bipolar depression.


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) ±95% confidence intervals (CIs).


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’s efficacy for depressive symptoms did not differ significantly in monotherapy vs augmentation studies (vs. placebo: p=0.98, I2=0%; vs active agents: p=0.48, I2=0%) or in unipolar vs bipolar patients (vs placebo: p=0.60, I2=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=–0.15, 95% CI=–0.27, –0.02, p=0.02, heterogeneity: p=0.24) and response (after removing one extreme outlier; RR=1.42, 95% CI=1.13–1.78; 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=0.85–0.92). Adverse effects and all-cause/specific-cause discontinuation were similar across all comparisons.


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.


Corresponding author

*Address for correspondence: Dr. Marco Solmi, Department of Neurosciences, University of Padua, Via Giustiniani, 2, 35128 Padova, Italy. (Email:


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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

  • Marco Solmi (a1) (a2), Nicola Veronese (a2) (a3), Leonardo Zaninotto (a2) (a4), Marc L. M. van der Loos (a5), Keming Gao (a6), Ayal Schaffer (a7), Catherine Reis (a7), Claus Normann (a8), Ion-George Anghelescu (a9) and Christoph U. Correll (a2) (a10) (a11) (a12) (a13)...


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