Lithium is one of the most studied agents used to augment the pharmacologic effect of antidepressantdrugs, particularly in refractory depression. We reviewed 22 case reports, 22 open trials, 5 opencomparison studies, and 9 placebo-controlled studies of lithium augmentation and 6 studies in whichantidepressants were added to, or coadministrated with, lithium. The efficacy of the augmentationtherapeutic strategy is supported by these analyses, involving 969 patients. The optimal dose and themost effective blood levels of lithium are unclear, but a reasonable strategy would be to start with lowdoses (600-900 mg/day) and, if necessary, to increase the doses to obtain a level in accordance withthe usual therapeutic range of blood levels (0.8-1.2 mEq/L). Some patients respond quickly, but othersneed a long and combined treatment; it is thus advantageous to prescribe lithium for at least 3 to 6weeks. Despite the fact that the mechanism of action of lithium augmentation is still unknown, allrefractory depressed patients can potentially be treated by lithium augmentation, particularly bipolarpatients, to obtain full prophylactic effect as soon as possible.
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