Lithium-discontinuation-induced treatment refractoriness revisited

Abstract

Background: Lithium is effective in the long-term treatment of bipolar disorder. Concerns have been raised about non-responsiveness after discontinuation and resuming previously effective lithium prophylaxis. We reviewed the available literature on this so-called lithium-discontinuation-induced treatment refractoriness (LDITR). Results: We found 11 case reports and six cohort studies including 403 patients addressing LDITR, and one nation-wide register study providing some additional data on LDITR. Pooling all cohort studies, the percentages of non-responders during re-treatment with lithium ranged from 3.6 to 27.7%, with an average of 17.3%. Non-responsiveness was associated with longer duration of lithium treatment before discontinuation, longer duration of bipolar disorder before start of lithium, faster tapering off lithium, and longer duration of discontinuation. Conclusions: There may be a subgroup in whom lithium discontinuation-induced treatment refractoriness exists. However, the vast majority of people respond when lithium is restarted. Moreover, it may be necessary to continue lithium beyond the first relapses to restore long-term prophylactic efficacy.