The association of the effect of lithium in the maintenance treatment of bipolar disorder with lithium plasma levels: a post hoc analysis of a double‐blind study comparing switching to lithium or placebo in patients who responded to quetiapine (Trial 144)

Abstract

Nolen WA, Weisler RH. The association of the effect of lithium in the maintenance treatment of bipolar disorder with lithium plasma levels: a post hoc analysis of a double‐blind study comparing switching to lithium or placebo in patients who responded to quetiapine (Trial 144). Bipolar Disord 2012: 00: 000–000. © 2012 John Wiley & Sons A/S.Published by Blackwell Publishing Ltd.Objectives: There is no robust proof that the efficacy of lithium in the prevention of manic and depressive episodes in bipolar disorder depends on its plasma level. This analysis aimed to compare the effect of lithium within the presumed therapeutic range of 0.6–1.2 mEq/L and below 0.6 mEq/L with that of placebo.Methods: We carried out a post hoc analysis of a double‐blind trial in which patients aged ≥18 years with bipolar I disorder (DSM‐IV) who had achieved stabilization from a manic, depressive, or mixed episode during open‐label treatment with quetiapine were randomized to continue quetiapine or to switch to lithium or placebo for up to 104 weeks. Of patients randomized to lithium, 201 obtained median lithium levels between 0.6 and 1.2 mEq/L, and 137 obtained median lithium levels <0.6 mEq/L. Their outcomes were compared with those of patients receiving placebo (n = 404). The primary outcome was time to recurrence of any mood event; additional outcomes included time to recurrence of a manic or depressive event.Results: Times to recurrence of any mood event as well as a manic or depressive event were significantly longer for the lithium 0.6–1.2 mEq/L group versus placebo and versus lithium <0.6 mEq/L, with no differences between lithium <0.6 mEq/L and placebo.Conclusions: The results support and expand previous findings that lithium should be dosed high enough to achieve plasma levels ≥0.6 mEq/L in order to achieve an effect in the prevention of both manic and depressive recurrences of bipolar I disorder. A major limitation is that the composition of the two lithium groups was not based on randomization.

Canadian Network for Mood and Anxiety Treatments (CANMAT) and International Society for Bipolar Disorders (ISBD) 2018 guidelines for the management of patients with bipolar disorder

“…Factors associated with overall good prognosis of BD include good treatment adherence, lack of early adversity, intermediate age at onset, good social support, and the absence of spontaneous rapid cycling406, 407 or features of a personality disorder 408…”

The International College of Neuro-Psychopharmacology (CINP) Treatment Guidelines for Bipolar Disorder in Adults (CINP-BD-2017), Part 2: Review, Grading of the Evidence, and a Precise Algorithm

“…Concerning lithium, it has been reported that only at plasma levels between 0.6 and 1.2 mEq/lt it is efficacious in the prevention of both manic and depressive episodes (Nolen and Weisler, 2013). Another posthoc analysis did not confirm its efficacy in the prevention of depressive episodes while it confirmed the efficacy of lamotrigine in the prevention of both manic and depressive episodes irrespective of index episode (Calabrese et al, 2003a; Goodwin et al, 2004).…”

Lithium efficacy in bipolar depression with flexible dosing: A six-week, open-label, proof-of-concept study

“…The similarity in the efficacy of standard vs. ‘sub-therapeutic’ lithium levels that was observed in the BD treatment in the present study has been indirectly addressed by recent studies on BD (9,16). The LiTMUS study evaluated symptomatic BD; however, unlike the current study it was solely based on the use of lithium monotherapy (9).…”