Abstract
Background
Several epidemiological studies have shown the inverse association of lithium levels in drinking water and suicide rates; however, it is necessary to perform a clinical study dealing with individual patients.
Methods
We analyzed 199 patients including 31 patients with suicide attempts, 21 patients with self-harm, and 147 control patients. All were transferred to a university emergency department suffering from intoxication or injury, were aged 20 or more years, and were alive at the start of the study. The exclusion criteria consisted of suffering from schizophrenia and a past or present history of lithium therapy. These exclusions were applied because it is difficult to determine whether their suicide attempt was induced by the intent to end their life or by psychotic symptoms such as auditory hallucinations, and if the patient had received lithium therapy, the association between the small amount of lithium taken from drinking water and food and serum lithium levels cannot be detected.
Results
There was a significant difference (p = 0.043) between the three groups whereby patients with suicide attempts had significantly lower lithium levels than control patients (p = 0.012) in males but not females. Multivariate logistic regression analysis with adjustment for age and gender revealed that patients with suicide attempts had significantly lower lithium levels than control patients (p = 0.032, odds ratio 0.228, 95% CI 0.059–0.883).
Limitations
The limitations of the present study are the nature of observational research which cannot reveal a causal relationship and the relatively small number of subjects.
Conclusions
The present findings suggest that higher serum lithium levels may be protective against suicide attempts in lithium therapy-naive individuals.
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References
Baldessarini RJ, Tondo L, Davis P, Pompili M, Goodwin FK, Hennen J (2006) Decreased risk of suicides and attempts during long-term lithium treatment: a meta-analytic review. Bipolar Disord 8:625–639
Bowen HJM (1966) Trace elements in biochemistry. Academic Press, USA
Cipriani A, Hawton K, Stockton S, Geddes JR (2013) Lithium in the prevention of suicide in mood disorders: updated systematic review and meta-analysis. BMJ 346:f3646
Ishii N, Terao T, Araki Y, Kohno K, Mizokami Y, Shiotsuki I, Hatano K, Makino M, Kodama K, Iwata N (2015) Low male suicide and lithium in drinking water. J Clin Psychiatry 76:319–326
Kabacs N, Memon A, Obinwa T, Stochl J, Perez J (2011) Lithium in drinking water and suicide rates across the East of England. Br J Psychiatry 198:406–407
Kapusta ND, König D (2015) Naturally occurring low-dose lithium in drinking water. J Clin Psychiatry 76:e373–e374
Kapusta ND, Mossaheb N, Etzersdorfer E, Hlavin G, Thau K, Willeit M, Praschak-Rieder N, Sonneck G, Leithner Dziubas K (2011) Lithium in drinking water and suicide mortality. Br J Psychiatry 198:346–350
Kessing LV, Søndergård L, Kvist K, Andersen PK (2005) Suicide risk in patients treated with lithium. Arch Gen Psychiatry 62:860–866
Liaugaudaite V, Mickuviene N, Raskauskiene N, Naginiene R, Sher L (2017) Lithium levels in the public drinking water supply and risk of suicide: a pilot study. J Trace Elem Med Biol 43:197–201
Ohgami H, Terao T, Shiotsuki I, Ishii N, Iwata N (2009) Lithium levels in drinking water and risk of suicide. Br J Psychiatry 194:464–465
Oquendo MA, Galfalvy HC, Currier D, Grunebaum MF, Sher L, Sullivan GM, Burke AK, Harkavy-Friedman J, Sublette ME, Parsey RV, Mann JJ (2011) Treatment of suicide attempters with bipolar disorder: a randomized clinical trial comparing lithium and valproate in the prevention of suicidal behavior. Am J Psychiatry 168:1050–1056
Pompili M, Vichi M, Dinelli E, Pycha R, Valera P, Albanese S, Lima A, De Vivo B, Cicchella D, Fiorillo A, Amore M, Girardi P, Baldessarini RJ (2015) Relationships of local lithium concentrations in drinking water to regional suicide rates in Italy. World J Biol Psychiatry 16:567–574
Schrauzer GN (2002) Lithium: occurrence, dietary intakes, nutritional essentiality. J Am Coll Nutr 21:14–21
Schrauzer GN, Shrestha KP (1990) Lithium in drinking water and the incidences of crimes, suicides, and arrests related to drug addictions. Biol Trace Elem Res 25:105–113
Sher L (2015) Suicide in men. J Clin Psychiatry 76:e371–e372
Shiotsuki I, Terao T, Ishii N, Takeuchi S, Kuroda Y, Kohno K, Mizokami Y, Hatano K, Tanabe S, Kanehisa M, Iwata N, Matusda S (2016) Trace lithium is inversely associated with male suicide after adjustment of climatic factors. J Affect Disord 189:282–286
Silverman MM, Berman AL, Sanddal ND, O'carroll PW, Joiner TE (2007) Rebuilding the tower of babel: a revised nomenclature for the study of suicide and suicidal behaviors. Part 2: suicide-related ideations, communications, and behaviors. Suicide Life Threat Behav 37:264–277
Song J, Sjölander A, Joas E, Bergen SE, Runeson B, Larsson H, Landén M, Lichtenstein P (2017) Suicidal behavior during lithium and valproate treatment: a within-individual 8-year prospective study of 50,000 patients with bipolar disorder. Am J Psychiatry 174:795–802
Sugawara N, Yasui-Furukori N, Ishii N, Iwata N, Terao T (2013) Lithium in tap water and suicide mortality in Japan. Int J Environ Res Public Health 10:6044–6048
Terao T (2008) Aggression, suicide, and lithium treatment. Am J Psychiatry 165:1356–1357
Terao T (2015) Is lithium potentially a trace element? World J Psychiatry 5:1–3
Terao T, Goto S, Inagaki M, Okamoto Y (2009) Even very low but sustained lithium intake can prevent suicide in the general population? Med Hypotheses 73:811–812
Toffol E, Hätönen T, Tanskanen A, Lönnqvist J, Wahlbeck K, Joffe G, Tiihonen J, Haukka J, Partonen T (2015) Lithium is associated with decrease in all-cause and suicide mortality in high-risk bipolar patients: a nationwide registry-based prospective cohort study. J Affect Disord 183:159–165
Wooderson SC, Gallagher P, Watson S, Young AH (2015) An exploration of testosterone levels in patients with bipolar disorder. Br J Psychiatry Open 1:136–138
Funding
This work was supported in part by the Japanese Society for the Promotion of Science as Grant-in-Aid for Scientific Research (C) (15K09838; Dr. Shiotsuki). The funder of the study had no role in study design, data collection, data analysis, data interpretation, or writing of the report.
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MK, TT, IS, KK, RT, TS, OS, NI, KH, and HH participated in study design and collecting data. MK and TT were responsible for writing the manuscript and had full access to all of the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis. All authors reviewed and provided comments on the manuscript. All authors have read and approved the final version of the manuscript for publication.
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This study was approved by the ethical committee of Oita University Faculty of medicine, and all subjects provided written informed consent. The authors assert that all procedures contributing to this work comply with the ethical standards of the relevant national and institutional committees on human experimentation and with the Helsinki Declaration of 1975, as revised in 2008.
Conflict of interest
Takeshi Terao served as a consultant to GlaxoSmithKline; he has received lecture fees from Eli Lilly, Pfizer, Otsuka, Mochida, Taisho-Toyama, MSD, Shionogi, Astellas, Daiichi-sankyo, and Meiji; and grants from Pfizer, Otsuka, Mochida, MSD, Astellas, Shionogi, Daiichisankyo, Tanabe-Mitsubishi, and Meiji. The other authors declare no conflict of interest.
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Kanehisa, M., Terao, T., Shiotsuki, I. et al. Serum lithium levels and suicide attempts: a case-controlled comparison in lithium therapy-naive individuals. Psychopharmacology 234, 3335–3342 (2017). https://doi.org/10.1007/s00213-017-4729-z
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DOI: https://doi.org/10.1007/s00213-017-4729-z