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CNS Spectr. 2016 Oct;21(5):403-418.

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.

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1Department of Neurosciences,University of Padova,Padova,Italy.
2Institute for Clinical Research and Education in Medicine,I.R.E.M.,Padua,Italy.
5Department of Psychiatry,Isala Klinieken,Location Sophia, Zwolle,the Netherlands.
6Mood & Anxiety Clinic,Mood Disorders Program,Department of Psychiatry,Case Western Reserve University School of Medicine/University Hospitals Case Medical Center,Cleveland,Ohio,USA.
7Mood & Anxiety Disorders Program,Department of Psychiatry,Sunnybrook Health Sciences Centre,University of Toronto,Toronto,Ontario,Canada.
8Department of Psychiatry and Psychotherapy,University Medical Center,Freiburg,Germany.
9Dr. Kurt Fontheim's Hospital for Mental Health,Department of Psychiatry, Liebenburg,Lower Saxony,Germany.



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.


Bipolar depression; bipolar disorder; lamotrigine; major depressive disorder; trials; unipolar depression

[Indexed for MEDLINE]

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