Lithium has been used for acute bipolar depression since its introduction for use in bipolar illness (El-Mallakh 1996). Controlled studies in bipolar patients invariably show significant improvement in the majority of acutely depressed bipolar patients (68%-100%, mean 68% response) (Goodwin et al. 1972; Mendels 1975). This is very similar to what might be expected of an antidepressant for unipolar illness (Stark and Hardi-son 1985), but is higher than the 51% efficacy rate of lithium in unipolar depression (El-Mallakh 1996). This clinically significant response rate stands in obvious contrast to general clinician experience with lithium. The discrepancy is explained by the fact that in the original controlled trials of lithium treatment, lithium levels were generally much higher (around 1.0 mM), than what is typically used by clinicians today (approximately 0.7 mM). There is ample evidence from lithium monother-apy studies (Gelenberg et al. 1989; Keller et al. 1992) and studies of lithium coadministration with an antidepressant (Nemeroff et al. 2001) that higher doses (and therefore blood levels) of lithium are more effective in treating and preventing depressive symptoms than lower doses. In their attempts to reduce the adverse-effect burden of lithium, clinicians are using it at doses that may be suboptimal for bipolar depression (El-Mallakh 1996).
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