Adjunctive Maintenance Lamotrigine for Pediatric Bipolar I Disorder: A Placebo-Controlled, Randomized Withdrawal Study.

This study aimed to compare the efficacy of lamotrigine versus placebo in 10- to 17-year-olds with bipolar I disorder (BP-I) who were receiving conventional bipolar disorder treatment. In this randomized withdrawal trial, patients with BP-I of at least moderate severity received lamotrigine during an ≤18-week open-label phase. Patients who maintained a stable lamotrigine dose for ≥2 weeks and Clinical Global Impression-Bipolar Severity of Illness (CGI-BP[S]) score of ≤3 for ≥6 consecutive weeks were randomized to double-blind lamotrigine or placebo for ≤36 weeks. Of 301 patients enrolled, 298 comprised the open-label intention-to-treat population, with 173 (58%) randomized. Of these patients, 41 (24%) completed the study. In the open-label phase, the mean (SD) baseline CGI-BP(S) rating was 4.4 (0.57), and the mean (standard error [SE]) time to stabilization was 101 (1.6) days. During the randomized phase, mean (SE) time to occurrence of a bipolar event (TOBE) for lamotrigine versus placebo (primary endpoint) was 155 (14.7) versus 50 (3.8), 163 (12.2) versus 120 (12.2), and 136 (15.4) versus 107 (13.8) days for the 3 index mood states (depressed, manic/hypomanic, mixed). The primary stratified log-rank analysis of TOBE was not statistically significant (hazard ratio [HR] = 0.63; p = .072); however, the prespecified Cox regression analysis favored lamotrigine (p = .047). In 13- to 17-year-olds, log-rank analysis of TOBE significantly favored lamotrigine (HR = 0.46; p = .015), but not in 10- to 12-year-olds (HR = 0.93; p = .877). Dermatologic events were reported in 4% (open-label phase) and 2% (randomized phase) of patients receiving lamotrigine. Suicidality-related adverse events were reported in 7% (open-label phase) and 7% (randomized phase) of patients receiving lamotrigine. Although the primary analysis failed to detect a benefit of add-on lamotrigine for BP-I in 10- to 17-year-olds, lamotrigine may be effective in a subset of older adolescents. Clinical trial registration information-Lamictal as Add-on Treatment for Bipolar I Disorder in Pediatric Patients; http://clinicaltrials.gov/; NCT00723450.