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.
OBJECTIVE
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.
1Department of Neurosciences,University of Padova,Padova,Italy.
Marco
http://orcid.org/0000-0003-4877-7233
M
Solmi
2Institute for Clinical Research and Education in Medicine,I.R.E.M.,Padua,Italy.
Nicola
http://orcid.org/0000-0002-9328-289X
N
Veronese
2Institute for Clinical Research and Education in Medicine,I.R.E.M.,Padua,Italy.
Leonardo
L
Zaninotto
5Department of Psychiatry,Isala Klinieken,Location Sophia, Zwolle,the Netherlands.
Marc L M
ML
van der Loos
6Mood & Anxiety Clinic,Mood Disorders Program,Department of Psychiatry,Case Western Reserve University School of Medicine/University Hospitals Case Medical Center,Cleveland,Ohio,USA.
Keming
K
Gao
7Mood & Anxiety Disorders Program,Department of Psychiatry,Sunnybrook Health Sciences Centre,University of Toronto,Toronto,Ontario,Canada.
Ayal
A
Schaffer
7Mood & Anxiety Disorders Program,Department of Psychiatry,Sunnybrook Health Sciences Centre,University of Toronto,Toronto,Ontario,Canada.
Catherine
C
Reis
8Department of Psychiatry and Psychotherapy,University Medical Center,Freiburg,Germany.
Claus
C
Normann
9Dr. Kurt Fontheim's Hospital for Mental Health,Department of Psychiatry, Liebenburg,Lower Saxony,Germany.
Ion-George
IG
Anghelescu
2Institute for Clinical Research and Education in Medicine,I.R.E.M.,Padua,Italy.
Christoph U
CU
Correll
D000927:Anticonvulsants / Q000627:therapeutic use*; D000928:Antidepressive Agents / Q000627:therapeutic use*; D018692:Antimanic Agents / Q000627:therapeutic use; D014150:Antipsychotic Agents / Q000627:therapeutic use; D001569:Benzodiazepines / Q000627:therapeutic use; D001714:Bipolar Disorder / Q000188:drug therapy*; D015283:Citalopram / Q000627:therapeutic use; D003863:Depression / Q000188:drug therapy*; D003865:Major Depressive Disorder / Q000188:drug therapy*; D004338:Drug Combinations; D005473:Fluoxetine / Q000627:therapeutic use; D006801:Humans; D007294:Inositol / Q000627:therapeutic use; D000077213:Lamotrigine; D008094:Lithium / Q000627:therapeutic use; D014227:Triazines / Q000627:therapeutic use*; D014803:Vitamin B Complex / Q000627:therapeutic use
D000927:Anticonvulsants; D000928:Antidepressive Agents; D018692:Antimanic Agents; D014150:Antipsychotic Agents; D004338:Drug Combinations; D014227:Triazines; C492572:olanzapine-fluoxetine combination; D005473:Fluoxetine; D015283:Citalopram; D014803:Vitamin B Complex; D001569:Benzodiazepines; D007294:Inositol; D008094:Lithium; D000077213:Lamotrigine
Bipolar depression; bipolar disorder; lamotrigine; major depressive disorder; trials; unipolar depression