Background: Because of negative studies of TCAs for prepubertal major depressive disorder (PMDD) and because of the potentially high switch rate of PMDD to prepubertal bipolarity (BP), it was hypothesized that lithium would be efficacious treatment for PMDD in children who also had family history (FH) predictors of future BP.
Methods: A double-blind, placebo-controlled, and pharmacokinetically dosed study of lithium for PMDD with FH predictors of future BP was performed. Random assignment was stratified by FH of BP-I or mania versus loaded/multigenerational (L/M) FH of MDD without BP-I or mania. Comprehensive assessments were done during a six week outpatient protocol that included weekly serum lithium levels.
Results: Mean age was 10.7+/-1.2 years; 17 subjects were randomized to active and 13 to placebo; 80% had FH of BP-I or mania (40% of parents had BP-I or mania); and 20% had FH of L/M MDD. Using both intent to treat with last observation carried forward (n = 30) and completer (n = 24) analyses, there were no significant differences on continuous or categorical measures between active and placebo groups. Mean serum lithium level was 0.99+/-0.16 mEq/l. There were no significant differences between mean total daily dose or mean serum lithium levels between responders and non-responders.
Limitations: Four subjects on active drug were discontinued because of dose-limiting side effects (three were cognitive impairment). Future studies of treatment for PMDD should consider alternative drugs.
Clinical relevance: Lithium was not significantly more efficacious than placebo for PMDD with FH predictors of future BP.