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Does Lithium Treatment Still Work?  Evidence of Stable Responses Over Three Decades

Ross J. Baldessarini, MD; Leonardo Tondo, MD
Arch Gen Psychiatry. 2000;57(2):187-190. doi:10.1001/archpsyc.57.2.187.
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To evaluate whether lithium treatment has been overvalued and may be no longer as effective as formerly, we reviewed published reports on long-term lithium treatment (1970-1996) as well as analyzing its clinical effects on 360 patients with DSM-IV bipolar disorder who entered into lithium maintenance monotherapy after 1970. Neither reported recurrence rates nor average proportions of time ill nor patient improvement of 50% or more during lithium maintenance therapy in a stable clinic setting has changed significantly since the 1970s. Unfavorable results in some settings may reflect accumulation over time of patients with complex, less treatment-responsive illnesses. Lithium is unmatched in research support for long-term clinical effectiveness against morbidity and mortality associated with depression or mania in bipolar I and II disorders. Data evaluated herein did not support suggestions that benefits of lithium have been exaggerated in the past or have been lost recently.

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Figure 1.

Recurrence rates (percentage of subjects per month) for studies found in the literature1538 vs year of reported treatment with lithium. Recurrence rates fell over the years (r = −0.445; P = .03), even when a small early study18 with an aberrantly high value was excluded (r = −0.474; P = .02).

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Figure 2.

Percentage of improvement in morbidity (as mean ± SEM episodes per year or percentage of time ill) in 360 Sardinian patients with bipolar I and II disorders during lithium maintenance treatment compared with themselves between illness onset and the start of maintenance treatment, between 1970 and 1996. There was no significant change in either measure of clinical benefit of lithium treatment (r = 0.023 and r = 0.007 for individual cases vs individual years of starting treatment, for episode frequency and percentage of time ill, respectively; for both, P≥.80).

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