Prophylaxis of Episodes

Lithium efficacy in preventing depressions in bipolar patients is not as clear. Early, long-term studies were not placebo-controlled, and have therefore been criticized regarding the methodology (Blackwell and Shepherd 1968). However, the best studies for the ability of lithium to prevent depressive relapse come from modern studies of lamotrigine, in which lithium is used as a positive control (Bowden et al. 2003; Cala-brese et al. 2003; Goodwin et al. 2004). These studies are extraordinarily well designed, since minimum lithium serum levels were 0.8 mM or higher, and since they included patients that were either recently manic (Bowden et al. 2003) or recently depressed (Calabrese et al. 2003). This is an important characterization, since the polarity of the index episode appears to predict the polarity of the next episode (Calabrese et al. 2004), and thus the outcome is different for the two groups (Bowden et al. 2003; Calabrese et al. 2003). In these studies, a total of 638 patients were randomly assigned to treatment with lithium (n = 167), lamotri-gine (n=280), or placebo (n = 191) and followed for 18 months. Outcome was need for intervention (not meeting DSM-IV criteria for an episode). Lithium was not effective in preventing depressive relapse in these patients compared with placebo (Goodwin et al. 2004).

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