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Letters to the Editor   |    
In Whom Does Lithium Work?
Gabrielle A. Carlson, M.D.
Am J Psychiatry 2013;170:559-559. doi:10.1176/appi.ajp.2012.13010038
View Author and Article Information

Dr. Carlson has received research funding from GlaxoSmithKline, Merck, NIMH, Otsuka, and Pfizer.

From the Departments of Psychiatry, Pediatrics, and Child and Adolescent Psychiatry, Stony Brook University School of Medicine, Stony Brook, N.Y.

Copyright © 2013 by the American Psychiatric Association

Accepted February , 2013.

To the Editor: In the January issue, Nierenberg et al. (1) try to answer an important question: Does lithium provide mood stabilization to a population of patients with lifetime bipolar I or II disorder who have chronic mood problems? According to the description of the sample, participants experienced an average of eight episodes per year, and although depressive episodes were fewer in number than manic or hypomanic episodes, patient scores on the Mini International Neuropsychiatric Interview at intake suggest that depression rather than mania accounted for more of their difficulties. Improvement in “mood” (it was not specified which mood) was the metric used to ascertain lithium’s success.

These results were contrasted to those of Gelenberg et al. (2), whose study sample consisted of patients with bipolar I disorder who had been euthymic for 2 months before intake so that relapse into mania or depression (not just mood improvement) could be determined. Moreover, those with four or more episodes were excluded from the study. In other words, the sample assessed by Nierenberg et al. would not have been in the Gelenberg et al. study, whose participants, granted, represented only a minority of mood-disordered patients (157 of 1,200). The comparison, therefore, is between apples and oranges.

While the Nierenberg et al. study is important in addressing what may be the majority of people with a diagnosis of bipolar I or II disorder (i.e., chronically mood unstable and primarily depressed [3]), it does not provide evidence to disprove lithium’s efficacy in the population for whom it was originally shown to be effective for prophylaxis and treatment: individuals with a positive family history, an interval course with a manic episode followed by a depressive episode and then a symptom-free episode, and fewer episodes (4, 5). In fact, the sample in the Nierenberg et al. study includes precisely those in whom we would not have expected a lithium response. The sample distinction is important; it is also important to remind clinicians that lithium was never touted as a panacea for general mood dysregulation.

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]
 
Judd  LL;  Akiskal  HS;  Schettler  PJ;  Endicott  J;  Maser  J;  Solomon  DA;  Leon  AC;  Rice  JA;  Keller  MB:  The long-term natural history of the weekly symptomatic status of bipolar I disorder.  Arch Gen Psychiatry 2002; 59:530–537
[CrossRef] | [PubMed]
 
Abou-Saleh  MT:  Who responds to prophylactic lithium therapy? Br J Psychiatry Suppl 1993; 163:20–26
 
Maj  M:  The effect of lithium in bipolar disorder: a review of recent research evidence.  Bipolar Disord 2003; 5:180–188
[CrossRef] | [PubMed]
 
References Container
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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]
 
Judd  LL;  Akiskal  HS;  Schettler  PJ;  Endicott  J;  Maser  J;  Solomon  DA;  Leon  AC;  Rice  JA;  Keller  MB:  The long-term natural history of the weekly symptomatic status of bipolar I disorder.  Arch Gen Psychiatry 2002; 59:530–537
[CrossRef] | [PubMed]
 
Abou-Saleh  MT:  Who responds to prophylactic lithium therapy? Br J Psychiatry Suppl 1993; 163:20–26
 
Maj  M:  The effect of lithium in bipolar disorder: a review of recent research evidence.  Bipolar Disord 2003; 5:180–188
[CrossRef] | [PubMed]
 
References Container
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