Korean Journal of Biological Psychiatry (생물정신의학)

The Korean Society of Biological Psychiatry (대한생물정신의학회)
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Subclinical Hypothyroidism in Patients with Bipolar Disorders Managed by Lithium or Valproic Acid

리튬 또는 발프로산으로 치료받은 양극성장애 환자의 무증상 갑상선저하증

  • Choi, Hyeon Man (Department of Psychiatry, Seoul National University Hospital) ;
  • Chang, Jae Seung (Department of Psychiatry and Behavioral Science, Seoul National University College of Medicine) ;
  • Kim, Jayoun (Department of Psychiatry, Seoul National University Bundang Hospital) ;
  • Kim, Jeong Hyun (Mental Health & Behavioral Medicine Services for Clinical, Seoul National University Bundang Hospital) ;
  • Choi, Jung Eun (Department of Psychiatry, Seoul Eunpyeong Hospital) ;
  • Ha, Tae Hyon (Department of Psychiatry and Behavioral Science, Seoul National University College of Medicine) ;
  • Ha, Kyooseob (Department of Psychiatry and Behavioral Science, Seoul National University College of Medicine)
  • 최현만 (서울대학교병원 정신건강의학과) ;
  • 장재승 (서울대학교 의과대학 정신과학교실) ;
  • 김자연 (분당서울대학교병원 정신건강의학과) ;
  • 김정현 (분당서울대학교병원 진료협력센터) ;
  • 최정은 (서울은평병원 정신건강의학과) ;
  • 하태현 (서울대학교 의과대학 정신과학교실) ;
  • 하규섭 (서울대학교 의과대학 정신과학교실)
  • Received : 2013.08.19
  • Accepted : 2013.09.02
  • Published : 2013.11.30
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Abstract

Objectives To investigate the pattern of subclinical hypothyroidism (SCH) in patients with bipolar disorders managed by lithium or valproic acid. Methods The study participants were 106 patients with DSM-IV bipolar disorders receiving planned maintenance treatment at the Mood Disorders Clinic of Seoul National University Bundang Hospital (aged between 17 and 64, mean duration of follow-up = 875.65 days). Using the bipolar disorder registry, thyroid function data were analyzed to assess the frequency of and the risk factors for SCH in patients managed by lithium (n = 64) or valproic acid (n = 42) for more than 5 months. Results Overall frequencies of SCH were 20.3% (13/64) in the lithium group, 14.3% (6/42) in the valproic acid group, and between the two groups there is no difference (p = 0.43). No differences were observed in the potential risk factors for SCH between the two groups including age, sex, subtype of bipolar disorder, baseline TSH, and concomitant antipsychotic use. In cases with SCH, thyroid-stimulating hormone (TSH) showed a tendency to increase at 3 month after the initiation of lithium or valproic acid. A gradual increase in the number of patients showing SCH was found within the first 3 years of medication. Conclusions With regular monitoring and careful assessment, there was no difference in the risk of SCH between lithium and valproic acid maintenance. The risk of mood stabilizer-associated SCH may gradually increase within 3 years following the commencement of medication, thereby mandating close monitoring for the first 3 years of treatment. Further studies with large sample size would be needed to confirm these findings.

Keywords

References

  1. Bauer M, Goetz T, Glenn T, Whybrow PC. The thyroid-brain interaction in thyroid disorders and mood disorders. J Neuroendocrinol 2008;20:1101-1114. https://doi.org/10.1111/j.1365-2826.2008.01774.x
  2. Bunevicius R, Prange AJ Jr. Psychiatric manifestations of Graves' hyperthyroidism: pathophysiology and treatment options. CNS Drugs 2006;20:897-909. https://doi.org/10.2165/00023210-200620110-00003
  3. Howland RH. Thyroid dysfunction in refractory depression: implications for pathophysiology and treatment. J Clin Psychiatry 1993; 54:47-54.
  4. Müller-Oerlinghausen B, Berghöfer A, Bauer M. Bipolar disorder. Lancet 2002;359:241-247. https://doi.org/10.1016/S0140-6736(02)07450-0
  5. Kupka RW, Luckenbaugh DA, Post RM, Leverich GS, Nolen WA. Rapid and non-rapid cycling bipolar disorder: a meta-analysis of clinical studies. J Clin Psychiatry 2003;64:1483-1494. https://doi.org/10.4088/JCP.v64n1213
  6. Vonk R, van der Schot AC, Kahn RS, Nolen WA, Drexhage HA. Is autoimmune thyroiditis part of the genetic vulnerability (or an endophenotype) for bipolar disorder? Biol Psychiatry 2007;62:135-140. https://doi.org/10.1016/j.biopsych.2006.08.041
  7. Bou Khalil R, Richa S. Thyroid adverse effects of psychotropic drugs: a review. Clin Neuropharmacol 2011;34:248-255. https://doi.org/10.1097/WNF.0b013e31823429a7
  8. Bocchetta A, Mossa P, Velluzzi F, Mariotti S, Zompo MD, Loviselli A. Ten-year follow-up of thyroid function in lithium patients. J Clin Psychopharmacol 2001;21:594-598. https://doi.org/10.1097/00004714-200112000-00009
  9. Vainionpaa LK, Mikkonen K, Rattya J, Knip M, Pakarinen AJ, Myllyla VV, et al. Thyroid function in girls with epilepsy with carbamazepine, oxcarbazepine, or valproate monotherapy and after withdrawal of medication. Epilepsia 2004;45:197-203. https://doi.org/10.1111/j.0013-9580.2004.26003.x
  10. Park YM, Kang SG, Lee BH, Lee HJ. Decreased thyroid function in Korean women with bipolar disorder receiving valproic acid. Gen Hosp Psychiatry 2011;33:200.e13-5.
  11. Kelly DL, Conley RR. Thyroid function in treatment-resistant schizophrenia patients treated with quetiapine, risperidone, or fluphenazine. J Clin Psychiatry 2005;66:80-84. https://doi.org/10.4088/JCP.v66n0111
  12. Rodondi N, Bauer DC. Subclinical hypothyroidism and cardiovascular risk: how to end the controversy. J Clin Endocrinol Metab 2013; 98:2267-2269. https://doi.org/10.1210/jc.2013-1875
  13. Rodondi N, den Elzen WP, Bauer DC, Cappola AR, Razvi S, Walsh JP, et al. Subclinical hypothyroidism and the risk of coronary heart disease and mortality. JAMA 2010;304:1365-1374. https://doi.org/10.1001/jama.2010.1361
  14. Zhu DF, Wang ZX, Zhang DR, Pan ZL, He S, Hu XP, et al. fMRI revealed neural substrate for reversible working memory dysfunction in subclinical hypothyroidism. Brain 2006;129(Pt 11):2923-2930. https://doi.org/10.1093/brain/awl215
  15. Baldini M, Colasanti A, Orsatti A, Airaghi L, Mauri MC, Cappellini MD. Neuropsychological functions and metabolic aspects in subclinical hypothyroidism: the effects of L-thyroxine. Prog Neuropsychopharmacol Biol Psychiatry 2009;33:854-859. https://doi.org/10.1016/j.pnpbp.2009.04.009
  16. Demartini B, Masu A, Scarone S, Pontiroli AE, Gambini O. Prevalence of depression in patients affected by subclinical hypothyroidism. Panminerva Med 2010;52:277-282.
  17. Waldman SA, Park D. Myxedema coma associated with lithium therapy. Am J Med 1989;87:355-356. https://doi.org/10.1016/S0002-9343(89)80168-8
  18. Bocchetta A, Cocco F, Velluzzi F, Del Zompo M, Mariotti S, Loviselli A. Fifteen-year follow-up of thyroid function in lithium patients. J Endocrinol Invest 2007;30:363-366. https://doi.org/10.1007/BF03346311
  19. Bocchetta A, Bernardi F, Burrai C, Pedditzi M, Loviselli A, Velluzzi F, et al. The course of thyroid abnormalities during lithium treatment: a two-year follow-up study. Acta Psychiatr Scand 1992;86:38- 41. https://doi.org/10.1111/j.1600-0447.1992.tb03222.x
  20. Mikati MA, Tarabay H, Khalil A, Rahi AC, El Banna D, Najjar S. Risk factors for development of subclinical hypothyroidism during valproic acid therapy. J Pediatr 2007;151:178-181. https://doi.org/10.1016/j.jpeds.2007.02.046
  21. Gardner DM, Murphy AL, O'Donnell H, Centorrino F, Baldessarini RJ. International consensus study of antipsychotic dosing. Am J Psychiatry 2010;167:686-693. https://doi.org/10.1176/appi.ajp.2009.09060802
  22. Helfand M; U.S. Preventive Services Task Force. Screening for subclinical thyroid dysfunction in nonpregnant adults: a summary of the evidence for the U.S. Preventive Services Task Force. Ann Intern Med 2004;140:128-141. https://doi.org/10.7326/0003-4819-140-2-200401200-00015
  23. Lazarus JH. Lithium and thyroid. Best Pract Res Clin Endocrinol Metab 2009;23:723-733. https://doi.org/10.1016/j.beem.2009.06.002
  24. Bocchetta A, Bernardi F, Pedditzi M, Loviselli A, Velluzzi F, Martino E, et al. Thyroid abnormalities during lithium treatment. Acta Psychiatr Scand 1991;83:193-198. https://doi.org/10.1111/j.1600-0447.1991.tb05523.x
  25. Vincent A, Baruch P, Vincent P. Early onset of lithium-associated hypothyroidism. J Psychiatry Neurosci 1993;18:74-77.
  26. Qiu L, Zha X. Effect of antipsychotics on serum level of thyroid hormones in schizophrenic patients. Laboratory Medicine 2007;1:18.
  27. Maarbjerg K, Vestergaard P, Schou M. Changes in serum thyroxine (T4) and serum thyroid stimulating hormone (TSH) during prolonged lithium treatment. Acta Psychiatr Scand 1987;75:217-221. https://doi.org/10.1111/j.1600-0447.1987.tb02778.x
  28. Emerson CH, Dysno WL, Utiger RD. Serum thyrotropin and thyroxine concentrations in patients recieving lithium carbonate. J Clin Endocrinol Metab 1973;36:338-346. https://doi.org/10.1210/jcem-36-2-338
  29. Zimmermann MB, Kohrle J. The impact of iron and selenium deficiencies on iodine and thyroid metabolism: biochemistry and relevance to public health. Thyroid 2002;12:867-878. https://doi.org/10.1089/105072502761016494
  30. Graf WD, Oleinik OE, Glauser TA, Maertens P, Eder DN, Pippenger CE. Altered antioxidant enzyme activities in children with a serious adverse experience related to valproic acid therapy. Neuropediatrics 1998;29:195-201. https://doi.org/10.1055/s-2007-973560
  31. Fagiolini A, Kupfer DJ, Scott J, Swartz HA, Cook D, Novick DM, et al. Hypothyroidism in patients with bipolar I disorder treated primarily with lithium. Epidemiol Psichiatr Soc 2006;15:123-127. https://doi.org/10.1017/S1121189X00004322