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Letters to the Editor   |    
Response to Carlson Letter
Andrew A. Nierenberg, M.D.; on behalf of the Bipolar Trials Network
Am J Psychiatry 2013;170:559a-560. doi:10.1176/appi.ajp.2013.13010038r
View Author and Article Information

The author’s disclosures accompany the original article.

Department of Psychiatry, Massachusetts General Hospital, Boston.

Copyright © 2013 by the American Psychiatric Association

Accepted February , 2013.

To the Editor: We appreciate Dr. Carlson’s comments on the main findings from our Lithium Moderate-Dose Use Study (LiTMUS) (1). LiTMUS included treatment-seeking patients who had at least some distress from symptoms in the context of a bipolar I or II diagnosis. Thus, in contrast to the participants included in the Gelenberg et al. study (2), this comparative effectiveness study included the types of patients who would be seen in clinical practice—and therefore the results of the study would be generalizable enough to inform clinicians. Additionally, the question addressed in LiTMUS was not whether or not lithium works, as implied by Dr. Carlson, but whether moderate doses of lithium would minimize side effects and add therapeutic benefit as a part of guideline-informed, evidence-based psychopharmacological treatment. We found that low levels of lithium did not have additive effects apart from a modest decrease in the use of second-generation antipsychotics. The study does not “disprove lithium’s efficacy,” but instead provides evidence that blood levels around 0.4 mEq/L may be insufficient to improve 6-month outcomes for this outpatient sample above and beyond what can be achieved with other medications. Nolen and Weisler (3) recently confirmed the lack of effectiveness for low levels of lithium for maintenance treatment.

We are applying this lesson from LiTMUS for another comparative effectiveness study funded by the Agency for Healthcare Research and Quality: the Bipolar CHOICE study (Clinical Health Outcomes Initiative in Comparative Effectiveness). Bipolar CHOICE has a similar design but will 1) use higher dosages and levels of lithium (>0.6 and <1.2 mEq/L) and 2) compare lithium with quetiapine for tolerability, safety, and effectiveness along with other treatments necessary to reach optimal outcomes.

Nierenberg  AA;  Friedman  ES;  Bowden  CL;  Sylvia  LG;  Thase  ME;  Ketter  T;  Ostacher  MJ;  Leon  AC;  Reilly-Harrington  N;  Iosifescu  DV;  Pencina  M;  Severe  JB;  Calabrese  JR:  Lithium Treatment Moderate-Dose Use Study (LiTMUS) for bipolar disorder: a randomized comparative effectiveness trial of optimized personalized treatment with and without lithium.  Am J Psychiatry 2013; 170:102–110
[CrossRef] | [PubMed]
 
Gelenberg  AJ;  Kane  JM;  Keller  MB;  Lavori  P;  Rosenbaum  JF;  Cole  K;  Lavelle  J:  Comparison of standard and low serum levels of lithium for maintenance treatment of bipolar disorder.  N Engl J Med 1989; 321:1489–1493
[CrossRef] | [PubMed]
 
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 2013; 15:100–109
[CrossRef] | [PubMed]
 
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References

Nierenberg  AA;  Friedman  ES;  Bowden  CL;  Sylvia  LG;  Thase  ME;  Ketter  T;  Ostacher  MJ;  Leon  AC;  Reilly-Harrington  N;  Iosifescu  DV;  Pencina  M;  Severe  JB;  Calabrese  JR:  Lithium Treatment Moderate-Dose Use Study (LiTMUS) for bipolar disorder: a randomized comparative effectiveness trial of optimized personalized treatment with and without lithium.  Am J Psychiatry 2013; 170:102–110
[CrossRef] | [PubMed]
 
Gelenberg  AJ;  Kane  JM;  Keller  MB;  Lavori  P;  Rosenbaum  JF;  Cole  K;  Lavelle  J:  Comparison of standard and low serum levels of lithium for maintenance treatment of bipolar disorder.  N Engl J Med 1989; 321:1489–1493
[CrossRef] | [PubMed]
 
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 2013; 15:100–109
[CrossRef] | [PubMed]
 
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