Skip to content

Bowden et al. A placebo-controlled 18-month trial of lamotrigine and lithium maintenance treatment in recently manic or hypomanic patients with bipolar I disorder. Archives of General Psychiatry. 2003;60:392–400. PMID 12695317

One-paragraph summary

This double-blind maintenance trial enrolled people with bipolar I disorder after a recent manic or hypomanic episode. During an eight-to-16-week open phase, lamotrigine was initiated and other psychotropics withdrawn; 175 of 349 entrants met stabilization criteria and were randomized to lamotrigine, lithium or placebo for up to 18 months. Both active treatments prolonged time to intervention for any mood episode versus placebo—lamotrigine P=.02 and lithium P=.006—but their polarity profiles differed: lamotrigine prolonged time to depressive intervention, P=.02, while lithium prolonged time to manic, hypomanic or mixed intervention, P=.006 (Bowden 2003, PMID 12695317).

Key findings

  • Screened/open-phase entrants: 349; randomized stabilizers: 175.
  • Randomized groups: lamotrigine 59, lithium 46, placebo 70.
  • Both lamotrigine and lithium delayed intervention for any mood episode.
  • Lamotrigine’s clearer polarity-specific effect was depressive prevention.
  • Lithium’s clearer polarity-specific effect was prevention of mania, hypomania or mixed episodes.
  • Lamotrigine’s most frequently reported adverse event was headache.

Limitations

  • The open lamotrigine stabilization phase created a strong enrichment design: only half of entrants were randomized.
  • Because all participants were initially exposed to lamotrigine, relative tolerability and generalizability are not neutral.
  • Randomized groups were modest, especially lithium with 46 participants.
  • “Time to intervention” includes clinician treatment decisions as well as syndromal recurrence.
  • The abstract reports P values rather than hazard ratios or absolute recurrence rates.

Why it matters

The trial made polarity-specific maintenance efficacy visible. It helped establish lamotrigine as a depression-weighted prevention option and reaffirmed lithium’s strength against elevated-polarity recurrence. It also became a canonical example of why enriched maintenance trials can show genuine efficacy while applying most directly to responders and tolerators, a central caveat in maintenance and relapse prevention.

Cited by wiki pages

  • Maintenance and relapse prevention
  • Lithium