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Letters to the Editor   |    
Differential Lithium Efficacy in Reducing Suicidal Behaviors Compared With Suicidal Thoughts
Todd D. Gould, M.D.; Adem Can, Ph.D.; Irving I. Gottesman, Ph.D., Hon. F.R.C.Psych.; Philippe Courtet, M.D., Ph.D.
Am J Psychiatry 2012;169:98-99. doi:10.1176/appi.ajp.2011.11081220
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The authors report no financial relationships with competing interests.

Accepted for publication in October 2011.

Baltimore

Minneapolis

Montpellier, France

Accepted October , 2011.

Copyright © American Psychiatric Association

To the Editor: We applaud the extensive effort and recognize the ethically challenging nature of designing and conducting the randomized clinical trial comparing lithium and valproate in the treatment of suicidal behavior (1) reported in the October 2011 issue of the Journal. Such studies are desperately needed to identify pharmacological treatment approaches that reduce suicide. The report by Oquendo et al. (1) should further encourage such experimental approaches. However, our concern is that the article's conclusions could discourage clinicians from prescribing lithium for at-risk bipolar patients.

Lithium therapy has been associated with a reduction in the risk of suicidal behavior, defined as a suicide attempt or completion (2). However, there exists limited evidence to suggest that planning for a suicide, a subtype of suicidal ideation, is attenuated by lithium therapy. In a recent consensus statement, experts argued that combining suicidal thinking and behavior should not be a standard endpoint for randomized controlled trials (3), and ideation per se does not have a well-documented biological basis. Oquendo et al. emphasize that they calculated power to detect a relative risk of 5 or greater, which compares favorably with the relative risks associated previously with not taking lithium versus taking lithium (relative risk=4.91, 95% CI=3.82–6.31) (2). However, sufficient power is only derived from including individuals with a plan for a suicidal act. Can the authors provide a power analysis only for suicidal behavior as an outcome, and discuss conclusions based on the outcome of that analysis?

A current hypothesis about the biological mechanism of lithium action in preventing suicide—consistent with available evidence—is that lithium does not reduce suicidal thoughts, but it reduces acting on such thoughts by decreasing impulsivity, aggression, or decision-making deficits, which are well-defined endophenotypes intermediate to suicidal behaviors (4). It is possible that lithium could have the greatest effect in preventing suicidal acts in patients who have a plan for suicide and that by intervening, as per the experimental design, the therapeutic effects of lithium would not be observed. We recognize that the experimental options were limited by ethical concerns that the authors were unmistakably correct to follow, but that does not reduce the rationale for considering that such a mechanism may be important.

Oquendo  MA;  Galfalvy  HC;  Currier  D;  Grunebaum  MF;  Sher  L;  Sullivan  GM;  Burke  AK;  Harkavy-Friedman  J;  Sublette  ME;  Parsey  RV;  Mann  JJ:  Treatment of suicide attempters with bipolar disorder: a randomized clinical trial comparing lithium and valproate in the prevention of suicidal behavior.  Am J Psychiatry 2011; 168:1050–1056
[PubMed]
[CrossRef]
 
Baldessarini  RJ;  Tondo  L;  Davis  P;  Pompili  M;  Goodwin  FK;  Hennen  J:  Decreased risk of suicides and attempts during long-term lithium treatment: a meta-analytic review.  Bipolar Disord 2006; 8:625–639
[PubMed]
[CrossRef]
 
Meyer  RE;  Salzman  C;  Youngstrom  EA;  Clayton  PJ;  Goodwin  FK;  Mann  JJ;  Alphs  LD;  Broich  K;  Goodman  WK;  Greden  JF;  Meltzer  HY;  Normand  SL;  Posner  K;  Shaffer  D;  Oquendo  MA;  Stanley  B;  Trivedi  MH;  Turecki  G;  Beasley  CM  Jr;  Beautrais  AL;  Bridge  JA;  Brown  GK;  Revicki  DA;  Ryan  ND;  Sheehan  DV:  Suicidality and risk of suicide: definition, drug safety concerns, and a necessary target for drug development: a consensus statement.  J Clin Psychiatry 2010; 71:e1–e21
[PubMed]
[CrossRef]
 
Kovacsics  CE;  Gottesman  II;  Gould  TD:  Lithium's antisuicidal efficacy: elucidation of neurobiological targets using endophenotype strategies.  Annu Rev Pharmacol Toxicol 2009; 49:175–198
[PubMed]
[CrossRef]
 
References Container
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References

Oquendo  MA;  Galfalvy  HC;  Currier  D;  Grunebaum  MF;  Sher  L;  Sullivan  GM;  Burke  AK;  Harkavy-Friedman  J;  Sublette  ME;  Parsey  RV;  Mann  JJ:  Treatment of suicide attempters with bipolar disorder: a randomized clinical trial comparing lithium and valproate in the prevention of suicidal behavior.  Am J Psychiatry 2011; 168:1050–1056
[PubMed]
[CrossRef]
 
Baldessarini  RJ;  Tondo  L;  Davis  P;  Pompili  M;  Goodwin  FK;  Hennen  J:  Decreased risk of suicides and attempts during long-term lithium treatment: a meta-analytic review.  Bipolar Disord 2006; 8:625–639
[PubMed]
[CrossRef]
 
Meyer  RE;  Salzman  C;  Youngstrom  EA;  Clayton  PJ;  Goodwin  FK;  Mann  JJ;  Alphs  LD;  Broich  K;  Goodman  WK;  Greden  JF;  Meltzer  HY;  Normand  SL;  Posner  K;  Shaffer  D;  Oquendo  MA;  Stanley  B;  Trivedi  MH;  Turecki  G;  Beasley  CM  Jr;  Beautrais  AL;  Bridge  JA;  Brown  GK;  Revicki  DA;  Ryan  ND;  Sheehan  DV:  Suicidality and risk of suicide: definition, drug safety concerns, and a necessary target for drug development: a consensus statement.  J Clin Psychiatry 2010; 71:e1–e21
[PubMed]
[CrossRef]
 
Kovacsics  CE;  Gottesman  II;  Gould  TD:  Lithium's antisuicidal efficacy: elucidation of neurobiological targets using endophenotype strategies.  Annu Rev Pharmacol Toxicol 2009; 49:175–198
[PubMed]
[CrossRef]
 
References Container
+
+

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