Rash in multicenter trials of lamotrigine in mood disorders: clinical relevance and management.
BACKGROUND
The rate of lamotrigine-associated rash in patients with mood disorders has not been well characterized. The objective of this report was to determine rash rates in clinical trials of lamotrigine in DSM-IV unipolar depression or bipolar disorder.


METHODS
A retrospective analysis was conducted of rates of lamotrigine-related rash in 12 multicenter studies, including 1 open study, 7 randomized controlled acute trials, and 4 randomized controlled maintenance trials from 1996 to 2001.


RESULTS
A total of 1955 patients were treated with lamotrigine in open-label settings (open-label phases preceding or following randomization and 1 stand-alone open-label study); 1198 patients received lamotrigine in controlled settings, and 1056 patients received placebo. In controlled settings, rates of benign rash were 8.3% and 6.4% in lamotrigine- and placebo-treated patients, respectively. Rates of serious rash were 0% with lamotrigine, 0.1% (N = 1) with placebo, and 0% with comparators. In the open-label setting, the overall rate of rash for lamotrigine was 13.1% (N = 257) and of serious rash, 0.1% (N = 2). One mild case of Stevens-Johnson syndrome not requiring hospitalization occurred in a patient treated with lamotrigine. There were no cases of toxic epidermal necrolysis in any setting.


CONCLUSIONS
Serious drug eruptions associated with lamotrigine were rare. Although rash is a potentially life-threatening reaction, the risk of serious rash due to lamotrigine should be weighed against more common risks associated with untreated or undertreated bipolar depression.
Calabrese
Joseph R
JR
Department of Psychiatry, Case Western Reserve University/University Hospitals of Cleveland, Cleveland, Ohio, USA. jrc8@po.cwru.edu
Sullivan
John R
JR
Bowden
Charles L
CL
Suppes
Trisha
T
Goldberg
Joseph F
JF
Sachs
Gary S
GS
Shelton
Melvin D
MD
Goodwin
Frederick K
FK
Frye
Mark A
MA
Kusumakar
Vivek
V
D000927:Anticonvulsants / Q000009:adverse effects* / Q000627:therapeutic use; D018692:Antimanic Agents / Q000009:adverse effects* / Q000627:therapeutic use; D001714:Bipolar Disorder / Q000188:drug therapy* / Q000453:epidemiology; D003430:Cross-Sectional Studies; D003865:Major Depressive Disorder / Q000188:drug therapy* / Q000453:epidemiology; D003875:Drug Eruptions / Q000453:epidemiology / Q000209:etiology*; D006801:Humans; D000077213:Lamotrigine; D015337:Multicenter Studies as Topic; D016032:Randomized Controlled Trials as Topic; D018570:Risk Assessment; D013262:Stevens-Johnson Syndrome / Q000139:chemically induced / Q000453:epidemiology / Q000209:etiology; D014227:Triazines / Q000009:adverse effects* / Q000627:therapeutic use
D000927:Anticonvulsants; D018692:Antimanic Agents; D014227:Triazines; D000077213:Lamotrigine