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

Abstract

OBJECTIVES

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

METHODS

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).

RESULTS

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.

CONCLUSIONS

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.

Authors+Show Affiliations

1Department of Neurosciences,University of Padova,Padova,Italy.2Institute for Clinical Research and Education in Medicine,I.R.E.M.,Padua,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.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.2Institute for Clinical Research and Education in Medicine,I.R.E.M.,Padua,Italy.

Pub Type(s)

Comparative Study
Journal Article
Meta-Analysis

Language

eng

PubMed ID

27686028

Citation

Solmi, Marco, et al. "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." CNS Spectrums, vol. 21, no. 5, 2016, pp. 403-418.
Solmi M, Veronese N, Zaninotto L, et al. 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. CNS Spectr. 2016;21(5):403-418.
Solmi, M., Veronese, N., Zaninotto, L., van der Loos, M. L., Gao, K., Schaffer, A., Reis, C., Normann, C., Anghelescu, I. G., & Correll, C. U. (2016). 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. CNS Spectrums, 21(5), 403-418.
Solmi M, et al. 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. CNS Spectr. 2016;21(5):403-418. PubMed PMID: 27686028.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - 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. AU - Solmi,Marco, AU - Veronese,Nicola, AU - Zaninotto,Leonardo, AU - van der Loos,Marc L M, AU - Gao,Keming, AU - Schaffer,Ayal, AU - Reis,Catherine, AU - Normann,Claus, AU - Anghelescu,Ion-George, AU - Correll,Christoph U, PY - 2016/10/1/entrez PY - 2016/10/1/pubmed PY - 2017/7/1/medline KW - Bipolar depression KW - bipolar disorder KW - lamotrigine KW - major depressive disorder KW - trials KW - unipolar depression SP - 403 EP - 418 JF - CNS spectrums JO - CNS Spectr VL - 21 IS - 5 N2 - OBJECTIVES: To meta-analytically summarize lamotrigine's effectiveness and safety in unipolar and bipolar depression. METHODS: 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). RESULTS: 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. CONCLUSIONS: 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. SN - 1092-8529 UR - https://www.unboundmedicine.com/medline/citation/27686028/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_ L2 - https://www.cambridge.org/core/product/identifier/S1092852916000523/type/journal_article DB - PRIME DP - Unbound Medicine ER -