Pattern of adverse drug reactions and serum level of maintenance lithium treatment in patients with bipolar affective disorder: a cross-sectional study in Eastern Nepal
Keywords:Adverse drug reactions, Bipolar affective disorder, Lithium, Eastern Nepal
Background: Benefits of lithium maintenance therapy in bipolar affective disorder (BPAD) are restricted by adverse drug reactions (ADRs) and low therapeutic index. The same dose of lithium has sub-therapeutic, therapeutic and supra-therapeutic serum level in different patients. The objective of this study was to describe the pattern of ADR and serum concentration of maintenance dose of lithium in patients with BPAD.
Methods: A cross-sectional study was conducted in patients diagnosed with BPAD and taking lithium monotherapy 900 mg daily at least for 6 months at outpatient department of psychiatry, B. P. Koirala institute of health sciences. Sociodemographic profile and relevant laboratory investigations were recorded on a self-designed proforma. Chi square test, ANOVA test and student’s t test were used for analysing the data at p value <0.05.
Results: Out of 123, 64 (52.0%) were female. Serum concentration ranged from 0.31 to 1.51 mmol/l with mean of 0.803 mmol/l and was in therapeutic range in 104 (84.6%) patients. At least one ADR was seen in 81 (65.9%) patients and hand tremor (43.6%) was the commonest ADR. Hypothyroidism and hyperthyroidism were seen in 9 (6.8%) and 6 (4.5%) patients, respectively. Occurrence of ADRs were more in female and was significantly significant (P value <0.05).
Conclusions: The serum level of lithium 900 mg/day varied widely and was in therapeutic range in majority of the patients. Prevalence of ADRs was 65.9%. Occurrence of ADRs were significantly more common in female patients and supra-therapeutic serum concentration of lithium. A prospective long-term study should be conducted to validate the study findings.
National Institute of Mental Health. Fact sheet: Bipolar Disorder, 2021. Available at: https://www.nimh.nih.gov/health/topics/bipolar-disorder/ Accessed on 2 May 2020.
Geddes JR, Miklowitz DJ. Treatment of bipolar disorder. Lancet. 2013;381(9878):1672-82.
Ferensztajn-Rochowiak E, Chłopocka-Woźniak M, Rybakowski JK. Ultra-long-term lithium therapy: all-important matters and a case of successful 50-year lithium treatment. Braz J Psychiatry. 2020:1516-44462020005030204.
McKnight RF, Adida M, Budge K, Stockton S, Goodwin GM, Geddes JR. Lithium toxicity profile: a systematic review and meta-analysis. Lancet. 2012;379(9817):721-8.
Perlick DA, Rosen RA, Kaczynski R. Medication nonadherence in bipolar disorder: a patient-centered review of research findings. Clin Approaches Bipolar Disord. 2004;3:56-64.
Horton S, Tuerk A, Cook D, Cook J, Dhurjati P. Maximum recommended dosage of lithium for pregnant women based on a PBPK model for lithium absorption. Adv Bioinformat. 2012;2012:352729.
Nolen WA, Licht RW, Young AH, Malhi GS, Tohen M, Vieta E, et al. ISBD/IGSLI Task Force on the treatment with lithium. What is the optimal serum level for lithium in the maintenance treatment of bipolar disorder? A systematic review and recommendations from the ISBD/IGSLI Task Force on treatment with lithium. Bipolar Disord. 2019;21(5):394-409.
Lim JU, Lee JH, Kim JS, Hwang YI, Kim TH, Lim SY, et al. Comparison of World Health Organization and Asia-Pacific body mass index classifications in COPD patients. Int J Chron Obstruct Pulmon Dis. 2017;12:2465-75.
Gelenberg AJ, Jefferson JW. Lithium tremor. J Clin Psychiatry. 1995;56(7):283-7.
Gitlin M. Lithium side effects and toxicity: prevalence and management strategies. Int J Bipolar Disord. 2016;4(1):27.
Gitlin MJ, Cochran SD, Jamison KR. Maintenance lithium treatment: side effects and compliance. J Clin Psychiatry. 1989;50(4):127-31.
Ackerman S, Nolan LJ. Body weight gain induced by psychotropic drugs: incidence, mechanisms and management. CNS Drugs. 1998;9:135-51.
Kleiner J, Altshuler L, Hendrick V, Hershman JM. Lithium-induced subclinical hypothyroidism: review of the literature and guidelines for treatment. J Clin Psychiatry. 1999;60(4):249-55.
Kirov G, Tredget J, John R, Owen MJ, Lazarus JH. A cross-sectional and a prospective study of thyroid disorders in lithium-treated patients. J Affect Disord. 2005;87(2-3):313-7.
Lazarus JH. Lithium and thyroid. Best Pract Res Clin Endocrinol Metab. 2009;23(6):723-33.
Kibirige D, Luzinda K, Ssekitoleko R. Spectrum of lithium induced thyroid abnormalities: a current perspective. Thyroid Res. 2013;6(1):3.