Lamotrigine in the acute treatment of bipolar depression: results of five double-blind, placebo-controlled clinical trials.
OBJECTIVE
The efficacy of lamotrigine as maintenance treatment for bipolar disorder (BD), particularly for delaying depressive episodes, is well established, but its efficacy in the acute treatment of bipolar depression is less clear. This paper reports the results of five randomized, double-blind, placebo-controlled trials of lamotrigine monotherapy for the acute treatment of bipolar depression.


METHODS
Adult subjects with bipolar I or II disorder experiencing a depressive episode were randomized to placebo or lamotrigine monotherapy (after titration, at a fixed dose of 50 mg or 200 mg daily in Study 1; a flexible dose of 100-400 mg daily in Study 2; or a fixed dose of 200 mg daily in Studies 3, 4 and 5) for 7-10 weeks.


RESULTS
Lamotrigine did not differ significantly from placebo on primary efficacy endpoints [17-item Hamilton Depression Rating Scale in Studies 1 and 2; Montgomery-Asberg Depression Rating Scale (MADRS) in Studies 3, 4 and 5]. In Study 1, lamotrigine significantly separated from placebo on some secondary measures of efficacy, including the MADRS, the Clinical Global Impressions-Severity (CGI-S) and the CGI-Improvement (CGI-I), but seldom differed on secondary efficacy endpoints for the other studies.


CONCLUSIONS
Lamotrigine monotherapy did not demonstrate efficacy in the acute treatment of bipolar depression in four out of five placebo-controlled clinical studies. Lamotrigine was well tolerated in the acute treatment of bipolar depression.
Calabrese
Joseph R
JR
Case Western Reserve University School of Medicine/University Hospitals of Cleveland, Cleveland, OH, USA. joseph.calabrese@uhhospitals.org
Huffman
Russell F
RF
White
Robin L
RL
Edwards
Suzanne
S
Thompson
Thomas R
TR
Ascher
John A
JA
Monaghan
Eileen T
ET
Leadbetter
Robert A
RA
D000328:Adult; D014150:Antipsychotic Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D001714:Bipolar Disorder / Q000175:diagnosis / Q000188:drug therapy*; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D007406:Interview, Psychological; D000077213:Lamotrigine; D008297:Male; D012720:Severity of Illness Index; D011795:Surveys and Questionnaires; D014227:Triazines / Q000008:administration & dosage / Q000627:therapeutic use*
D014150:Antipsychotic Agents; D014227:Triazines; D000077213:Lamotrigine