Re-exploring Saliva as an Analyte in Estimation of Lithium in Stable Bipolar Patients – A Pilot Study in a Tertiary Care Hospital in West Bengal
Keywords:TDM, Bipolar disorder, Lithium, Pharmacokinetic model, Atomic absorption spectrometry
Background: Lithium a frequently prescribed drug in the treatment of bipolar affective disorder, due to its inherent adverse potential and narrow therapeutic index, demands for regular therapeutic drug monitoring (TDM). Although the term TDM seems to be tedious, the most tedious job is to collect blood samples from patients with psychiatric illness. In this study, we aimed to find out an alternative method to serum lithium monitoring. Although saliva as an analyte is non-popular, the presence of lithium in the saliva in patients who consumes lithium makes procedure of collection easier. The rate of elimination of lithium is slower from saliva than from serum, which makes the concentration of lithium higher in saliva than in blood. Lithium elimination follows two compartment pharmacokinetic models, where important part of compartment is saliva and salivary glands. The trouble of repeated venipuncture can be done away with, if a non-invasive method for serum lithium concentration is taken into consideration. An alternative method of determining lithium level could be saliva. The aim of this study was to find out whether estimation of lithium in saliva can replace serum lithium estimation. Materials and Methods: In this cross-sectional study, 60 stable patients of bipolar disorder attending psychiatry outdoor on lithium therapy for 3 months or more were considered. After informed consent documentation serum and saliva samples were collected after 12 h of last dose of lithium carbonate intake. Assessment was done based on atomic absorption spectrometry. After statistical analysis, it was found that that there is a correlation between serum and saliva lithium level. The 60 patients were divided into two groups, consisting of 30 patients each. Linear regression was done in both the groups thereby the formula obtained from the first group, was utilized to calculate the saliva concentration form serum concentration. The mean values were compared at the last. Results: The mean serum lithium obtained was 0.99 ± 0.257 SD (mEq/L) and mean salivary lithium obtained was 1.63 ± 0.51 SD (mEq/L) in Group 1. Whereas, the mean serum lithium obtained was 0.79 ± 0.26 SD (mEq/L) and mean salivary lithium obtained was 1.67 ± 0.49 SD (mEq/L) in group 2. Lithium concentration from both the samples showed a positive correlation as obtained from the scatter plot. Conclusion: Salivary Li estimation seems to yield positive results, yet more research should be done in this regard. Since saliva method for estimation is non-invasive, the idea could be utilized in designing other devices
Malhi GS, Gessler D, Outhred T. The use of lithium for the treatment of bipolar disorder: Recommendations from clinical practice guidelines. J Affect Disord 2017;217:266-80.
Cipriani A, Hawton K, Stockton S, Geddes JR.. Lithium in the Prevention of Suicide in Mood Disorders: Updated Systematic Review and Meta-analysis. In: Database of Abstracts of Reviews of Effects (DARE): Quality-assessed Reviews. New York: Centre for Reviews and Dissemination; 2013.
Song J, Sjölander A, Joas E, Bergen SE, Runeson B, Larsson H, 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.
Jakobsson E, Argüello-Miranda O, Chiu SW, Fazal Z, Kruczek J, Nunez-Corrales S, et al. Towards a unified understanding of lithium action in basic biology and its significance for applied biology. J Membr Biol 2017;250:587-604.
Kamali M, Krishnamurthy VB, Baweja R, Lithium. In: Schatzberg AF, Nemeroff CB, editors. The American Psychiatric Association Publishing Textbook of Psychopharmacology. 5th ed. Arlington, VA: American Psychiatric Association Publishing; 2017. p. 889.
Alda M. Pharmacokinetics of lithium. In: Bauer M, Grof P, editors. Lithium in Neuropsychiatry. United Kingdom: Informa UK Ltd.; 2006. p. 321.
Labbate LA, Fava M, Rosenbaum JF. Drugs for treatment of bipolar disorders. In: Handbook of Psychiatric Drug Therapy. 6th ed. Philadelphia, PA: Lippincott Williams and Wilkins; 2010.
Griswold KS, Pessar LF. Management of bipolar disorder. Am Fam Physician 2000;62:1343-53.
Glick ID. Undiagnosed bipolar disorder: New syndromes and new treatments. Prim Care Companion J Clin Psychiatry 2004;6:27-33.
Weintraub D, Comella CL, Horn SS. Part 3: Neuropsychiatric symptoms. Am J Manag Care 2008;14:S59-69. Available from: https://www.ajmc.com/view/mar08-3053ps59-s69. [Last accessed on 2020 Sep 18].
Osterberg L, Blaschke T. Adherence to medication. N Engl J Med 2005;353:487-97.
Nolen WA, Weisler RH. The association of the effect of lithium in the maintenance treatment of bipolar disorder with lithium plasma levels: A post hoc analysis of a double-blind study comparing switching to lithium or placebo in patients who responded to quetiapine (Trial 144). Bipolar Disord 2013;15:100-9.
InstaRead lithium system. Med Lett Drugs Ther 2005;47:82-3.
Karki SD, Carson SW, Holden JM. Effect of assay methodology on the prediction of lithium maintenance dosage. DICP 1989;23:372-5.
Magnin JL, Decosterd LA, Centeno C, Burnier M, Diezi J, Biollaz J. Determination of trace lithium in biological fluids using graphite furnace atomic absorption spectrophotometry: Variability of urine matrices circumvented by cation exchange solid phase extraction. Pharm Acta Helv 1996;71:237-46.
Halder A, Singh S, Adhikari A, Ghosh S, Deep S, Saha D, et al. NaLiK, an indigenous device for rapid, reliable and simultaneous assessment of sodium, lithium and potassium for management of fluid balance and bipolar disorder in human subjects. J Anal At Spectrom 2019;34:1875-81.
Langman JL. The use of oral fluid for therapeutic drug manangement. Ann N Y Acad Sci 2007;1098:145-66.
Serdarević N, Kozjek F, Malešič I. Saliva and serum lithium monitoring in hospitalized patients and possibility to replace serum to saliva. Bosn J Basic Med Sci 2006;6:32-5.
Mathew RJ, Claghorn JL, Fenimore D, Davis C, Weinman M. Saliva lithium and lithium therapy. Am J Psychiatry 1979;136:851.
Sims A, White A, Garvey K. Problems associated with the analysis and interpretation of saliva lithium. Br J Psychiatry 1978;132:152-4.
El-Mallakh RS, Linder M, Valdes R, Looney S. Dialysis of saliva improves accuracy of saliva lithium determinations. Bipolar Disord 2004;6:87-9.
How to Cite
Copyright (c) 2021 Debajyoti Saha, Nabarun Gupta, Sabnam Ara Begum, Malay Kumar Ghoshal, Santanu Kumar Tripathi, Sukanta Sen
This work is licensed under a Creative Commons Attribution 4.0 International License.
Asian Pacific Journal of Health Sciences applies the Creative Commons Attribution (CC-BY) license to published articles. Under this license, authors retain ownership of the copyright for their content, but they allow anyone to download, reuse, reprint, modify, distribute and/or copy the content as long as the original authors and source are cited. Appropriate attribution can be provided by simply citing the original article.