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Letters to the Editor
Published Online: 5 January 2018

Mixed Features in Bipolar I Disorder and the Effect of Lithium on Suicide

To the Editor: We read with much interest the article by Song et al. (1), published in the August 2017 issue of the Journal, showing that rates of suicide-related events in bipolar disorder were significantly decreased during lithium treatment, but not during valproate treatment, using a long follow-up period and the largest sample ever reported. Surprisingly, however, subgroup analyses showed a nonsignificantly reduced rate of suicide-related events during lithium treatment for patients with bipolar I disorder (hazard ratio=0.85, 95% CI=0.67–1.09) and a significantly reduced rate for patients with bipolar II disorder (hazard ratio=0.62, 95% CI=0.46–0.82). This finding suggests that lithium can prevent suicide in bipolar II disorder but not in bipolar I disorder, which is not in line with our clinical experience.
We wonder if Song et al. used DSM-IV-TR criteria to diagnose all patients with mixed episodes as suffering from bipolar I disorder. As shown by themselves, suicide-related events were not significantly reduced during lithium treatment for patients with mixed episodes (hazard ratio=0.87, 95% CI=0.74–1.03), suggesting that lithium may not be effective for suicide prevention in patients with mixed episodes. If the authors included such individuals in their cohort of patients with bipolar I disorder, the effect of lithium on suicide prevention in bipolar I disorder might have been attenuated to a nonsignificant level.
In fact, other researchers have reported that mixed states had the highest incidence rate of suicide attempts (765 per 1,000 person-years), whereas major depressive episode, depressive symptoms, euthymia, hypomania, and mania had incidence rates of 354, 70, 6, 0, and 0 per 1,000 person-years, respectively (2). In addition, a meta-analysis showed a nonsignificant pooled risk ratio (1.03, 95% CI=0.88–1.20) for comparison of bipolar I disorder relative to bipolar II disorder (3). Therefore, the suicide rate may depend on mixed state and depressive episode but not on bipolar subtype (bipolar I or II).
We recommend that Song et al. rediagnose their patients using a specifier of “with mixed features” (DSM-5), which can be added not only to bipolar I disorder but also to bipolar II disorder. It is likely that the hazard ratio of suicide-related events in patients with bipolar I disorder will be increased to a significant level, whereas that of patients with bipolar II disorder will be decreased but within a significant level. This new conclusion would suggest that lithium may be effective for suicide prevention in both bipolar I and II disorders.

References

1.
Song J, Sjölander A, Joas E, et al: Suicidal behavior during lithium and valproate treatment: a within-individual 8-year prospective study of 50,000 patients with bipolar disorder. Am J Psychiatry 2017; 174:795–802
2.
Pallaskorpi S, Suominen K, Ketokivi M, et al: Incidence and predictors of suicide attempts in bipolar I and II disorders: a 5-year follow-up study. Bipolar Disord 2017; 19:13–22
3.
Tondo L, Pompili M, Forte A, et al: Suicide attempts in bipolar disorders: comprehensive review of 101 reports. Acta Psychiatr Scand 2016; 133:174–186

Information & Authors

Information

Published In

Go to American Journal of Psychiatry
Go to American Journal of Psychiatry
American Journal of Psychiatry
Pages: 80
PubMed: 29301424

History

Accepted: September 2017
Published in print: January 01, 2018
Published online: 5 January 2018

Keywords

  1. Anticonvulsants
  2. Epidemiology
  3. Lithium
  4. Mood Disorders-Bipolar
  5. Suicide

Authors

Details

Takeshi Terao, M.D., Ph.D. [email protected]
From the Department of Neuropsychiatry, Oita University Faculty of Medicine, Oita, Japan.
Masayuki Kanehisa, M.D.
From the Department of Neuropsychiatry, Oita University Faculty of Medicine, Oita, Japan.
Ippei Shiotsuki, M.D., Ph.D.
From the Department of Neuropsychiatry, Oita University Faculty of Medicine, Oita, Japan.
Nobuyoshi Ishii, M.D., Ph.D.
From the Department of Neuropsychiatry, Oita University Faculty of Medicine, Oita, Japan.

Notes

Address correspondence to Dr. Terao ([email protected]).

Funding Information

The authors report no financial relationships with commercial interests.

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