Skip to main content
×
×
Home

Use of lithium and cancer risk in patients with bipolar disorder: population-based cohort study

  • Ru-Yu Huang (a1), Kun-Pin Hsieh (a2), Wan-Wen Huang (a1) and Yi-Hsin Yang (a3)
Abstract
Background

Lithium inhibits glycogen synthase kinase-3, which is an enzyme involved in the pathogenesis of cancer.

Aims

To investigate the association between lithium and cancer risk in patients with bipolar disorder.

Method

A retrospective cohort study was designed using the National Health Insurance Research Database (NHIRD) in Taiwan. Patients using lithium comprised the index drug group and patients using anticonvulsants only comprised the control group. Time-dependent Cox regression was used to evaluate the hazard ratios (HRs) for risk of cancer.

Results

Compared with anticonvulsant-only exposure, lithium exposure was associated with significantly lower cancer risk (HR = 0.735, 95% CI 0.554–0.974). The hazard ratios for the first, second and third tertiles of the cumulative defined daily dose were 0.762 (95% CI 0.516–1.125), 0.919 (95% CI 0.640–1.318) and 0.552 (95% CI 0.367–0.831), respectively.

Conclusions

Lithium is associated with reduced overall cancer risk in patients with bipolar disorder. A dose–response relationship for cancer risk reduction was observed.

    • Send article to Kindle

      To send this article to your Kindle, first ensure no-reply@cambridge.org is added to your Approved Personal Document E-mail List under your Personal Document Settings on the Manage Your Content and Devices page of your Amazon account. Then enter the ‘name’ part of your Kindle email address below. Find out more about sending to your Kindle. Find out more about sending to your Kindle.

      Note you can select to send to either the @free.kindle.com or @kindle.com variations. ‘@free.kindle.com’ emails are free but can only be sent to your device when it is connected to wi-fi. ‘@kindle.com’ emails can be delivered even when you are not connected to wi-fi, but note that service fees apply.

      Find out more about the Kindle Personal Document Service.

      Use of lithium and cancer risk in patients with bipolar disorder: population-based cohort study
      Available formats
      ×
      Send article to Dropbox

      To send this article to your Dropbox account, please select one or more formats and confirm that you agree to abide by our usage policies. If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your <service> account. Find out more about sending content to Dropbox.

      Use of lithium and cancer risk in patients with bipolar disorder: population-based cohort study
      Available formats
      ×
      Send article to Google Drive

      To send this article to your Google Drive account, please select one or more formats and confirm that you agree to abide by our usage policies. If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your <service> account. Find out more about sending content to Google Drive.

      Use of lithium and cancer risk in patients with bipolar disorder: population-based cohort study
      Available formats
      ×
Copyright
Corresponding author
Yi-Hsin Yang, PhD, School of Pharmacy, College of Pharmacy, Kaohsiung Medical University, 100, Shih-Chuan 1st Road, Kaohsiung, 807, Taiwan. Email: yihsya@kmu.edu.tw
Footnotes
Hide All

These authors contributed equally to the work.

Declaration of interest

None.

Footnotes
References
Hide All
1 Takahashi-Yanaga, F. Activator or inhibitor? GSK-3 as a new drug target. Biochem Pharmacol 2013; 86: 191–9.
2 McCubrey, JA, Davis, NM, Abrams, SL, Montalto, G, Cervello, M, Basecke, J, et al. Diverse roles of GSK-3: tumor promoter-tumor suppressor, target in cancer therapy. Adv Biol Regul 2014; 54: 176–96.
3 McCubrey, JA, Steelman, LS, Bertrand, FE, Davis, NM, Sokolosky, M, Abrams, SL, et al. GSK-3 as potential target for therapeutic intervention in cancer. Oncotarget 2014; 5: 2881–911.
4 Brown, KM, Tracy, DK. Lithium: the pharmacodynamic actions of the amazing ion. Ther Adv Psychopharmacol 2013; 3: 163–76.
5 Severus, E, Taylor, MJ, Sauer, C, Pfennig, A, Ritter, P, Bauer, M, et al. Lithium for prevention of mood episodes in bipolar disorders: systematic review and meta-analysis. Int J Bipolar Disord 2014; 2: 117.
6 Cohen, Y, Chetrit, A, Cohen, Y, Sirota, P, Modan, B. Cancer morbidity in psychiatric patients: influence of lithium carbonate treatment. Med Oncol 1998; 15: 32–6.
7 Cheng, CL, Kao, YH, Lin, SJ, Lee, CH, Lai, ML. Validation of the National Health Insurance Research Database with ischemic stroke cases in Taiwan. Pharmacoepidemiol Drug Saf 2011; 20: 236–42.
8 National Health Insurance Research Database, Taiwan. Data Subset. NHIRD, 2015 (http://nhird.nhri.org.tw/en/Data_Subsets.html).
9 World Health Organization. International Statistical Classification of Diseases and Related Health Problems (ICD-9). WHO, 1978.
10 Young, LT. What exactly is a mood stabilizer? J Psychiatry Neurosci 2004; 29: 87–8.
11 Bowden, CL. Anticonvulsants in bipolar disorders: current research and practice and future directions. Bipolar Disord 2009; 11: 2033.
12 WHO Collaborating Centre for Drug Statistics Methodology. ATC/DDD Index 2015. WHOCC, 2015 (http://www.whocc.no/atc_ddd_index/).
13 Deyo, RA, Cherkin, DC, Ciol, MA. Adapting a clinical comorbidity index for use with ICD-9-CM administrative databases. J Clin Epidemiol 1992; 45: 613–9.
14 Gerhard, T, Devanand, DP, Huang, C, Crystal, S, Olfson, M. Lithium treatment and risk for dementia in adults with bipolar disorder: population-based cohort study. Br J Psychiatry 2015; 207: 4651.
15 Pottegard, A, Friis, S, Andersen, M, Hallas, J. Use of benzodiazepines or benzodiazepine related drugs and the risk of cancer: a population-based case-control study. Br J Clin Pharmacol 2013; 75: 1356–64.
16 Brookhart, MA, Wyss, R, Layton, JB, Sturmer, T. Propensity score methods for confounding control in nonexperimental research. Circ Cardiovasc Qual Outcomes 2013; 6: 604–11.
17 Austin, PC. The performance of different propensity score methods for estimating marginal hazard ratios. Stat Med 2013; 32: 2837–49.
18 Kaae, J, Carstensen, L, Wohlfahrt, J, Melbye, M, Boyd, HA. Epilepsy, antiepileptic medication use and risk of cancer. Int J Cancer 2014; 134: 932–8.
19 Singh, G, Bell, GS, Driever, PH, Sander, JW. Cancer risk in people with epilepsy using valproate-sodium. Acta Neurol Scand 2012; 125: 234–40.
20 Hallas, J, Friis, S, Bjerrum, L, Stovring, H, Narverud, SF, Heyerdahl, T, et al. Cancer risk in long-term users of valproate: a population-based case-control study. Cancer Epidemiol Biomarkers Prev 2009; 18: 1714–9.
21 Kang, H, Gillespie, TW, Goodman, M, Brodie, SA, Brandes, M, Ribeiro, M, et al. Long-term use of valproic acid in US veterans is associated with a reduced risk of smoking-related cases of head and neck cancer. Cancer 2014; 120: 1394–400.
22 Boursi, B, Lurie, I, Mamtani, R, Haynes, K, Yang, YX. Anti-depressant therapy and cancer risk: a nested case-control study. Eur Neuropsychopharmacol 2015; 25: 1147–57.
23 Lee, HK, Eom, CS, Kwon, YM, Ahn, JS, Kim, S, Park, SM. Meta-analysis: selective serotonin reuptake inhibitors and colon cancer. Eur J Gastroenterol Hepatol 2012; 24: 1153–7.
24 Walker, AJ, Card, T, Bates, TE, Muir, K. Tricyclic antidepressants and the incidence of certain cancers: a study using the GPRD. Br J Cancer 2011; 104: 193–7.
25 Fond, G, Macgregor, A, Attal, J, Larue, A, Brittner, M, Ducasse, D, et al. Antipsychotic drugs: pro-cancer or anti-cancer? A systematic review. Med Hypotheses 2012; 79: 3842.
26 Lin, GM, Chen, YJ, Kuo, DJ, Jaiteh, LE, Wu, YC, Lo, TS, et al. Cancer incidence in patients with schizophrenia or bipolar disorder: a nationwide population-based study in Taiwan, 1997–2009. Schizophr Bull 2013; 39: 407–16.
27 Hung, Y-N, Yang, S-Y, Huang, M-C, Lung, F-W, Lin, S-K, Chen, K-Y, et al. Cancer incidence in people with affective disorder: nationwide cohort study in Taiwan, 1997–2010. Br J Psychiatry 2014; 205: 183–8.
28 Health Promotion Administration, Ministry of Health and Welfare. Cancer Registry Annual Report 2010, Taiwan. Health Promotion Administration, Ministry of Health and Welfare, 2010 (http://www.hpa.gov.tw/BHPNet/Web/Stat/StatisticsShow.aspx?No=200911300001).
29 Grunze, H, Vieta, E, Goodwin, GM, Bowden, C, Licht, RW, Moller, HJ, et al. The World Federation of Societies of Biological Psychiatry (WFSBP) guidelines for the biological treatment of bipolar disorders: update 2012 on the long-term treatment of bipolar disorder. World J Biol Psychiatry. 2013; 14: 154219.
30 Bai, YM, Chang, CJ, Tsai, SY, Chen, YC, Hsiao, MC, Li, CT, et al. Taiwan consensus of pharmacological treatment for bipolar disorder. J Chin Med Assoc 2013; 76: 547–56.
31 Rowe, MK, Wiest, C, Chuang, DM. GSK-3 is a viable potential target for therapeutic intervention in bipolar disorder. Neurosci Biobehav Rev 2007; 31: 920–31.
Recommend this journal

Email your librarian or administrator to recommend adding this journal to your organisation's collection.

The British Journal of Psychiatry
  • ISSN: 0007-1250
  • EISSN: 1472-1465
  • URL: /core/journals/the-british-journal-of-psychiatry
Please enter your name
Please enter a valid email address
Who would you like to send this to? *
×
Type Description Title
PDF
Supplementary materials

Huang et al. supplementary material
Supplementary Table S1-S4

 PDF (583 KB)
583 KB

Metrics

Altmetric attention score

Full text views

Total number of HTML views: 0
Total number of PDF views: 38 *
Loading metrics...

Abstract views

Total abstract views: 138 *
Loading metrics...

* Views captured on Cambridge Core between 2nd January 2018 - 23rd April 2018. This data will be updated every 24 hours.

Use of lithium and cancer risk in patients with bipolar disorder: population-based cohort study

  • Ru-Yu Huang (a1), Kun-Pin Hsieh (a2), Wan-Wen Huang (a1) and Yi-Hsin Yang (a3)
Submit a response

eLetters

No eLetters have been published for this article.

×

Reply to: Submit a response


Your details


Conflicting interests

Do you have any conflicting interests? *