臨 SSRIs 引 起 的 低 鈉 血 症 高 雄 醫 大 附 設 中 和 紀 念 醫 院 劑 部 師 陳 宗 賢 鄭 幸 宜 涂 淑 倩 鐘 堂 嘉 摘 要 (selective serotonin reuptake inhibitors, SSRIs) (hyponatremia) SSRIs (syndrome of inappropriate antidiuretic hormone secretion, SIADH) SSRIs SSRIs selective serotonin-reuptake inhibitors hyponatremia 壹 前 言 1988 fluoxetine (Prozac) FDA sertraline paroxetine fluvoxamine citalopram escitalopram (serotonin) histamine cholinergic 1-adrenergic (tricyclic antidepressants, TCAs) TCAs (1999-2009) SSRIs 35% 1 ( 65 ) 54.7% 2 SSRIs SSRIs 貳 個 案 描 述 77 25 80 THE JOURNAL OF TAIWAN PHARMACY Vol.30 No.2 Jun. 30 2014
lorazepam (Lowen) 0.5 mg 1 Tab BID sertraline (Serlin) 50 mg 1 Tab HS (Na + =121 mmol/l) 3 sertraline warfarin (Coumadin) 5 mg 0.5 Tab HS escitalopram (Lexapro) 10 mg 0.5 Tab HS (Na + =117 mmol/l) 0.9% N/ S 500 ml 3 g (Na + =122 mmol/ L) 26 escitalopram duloxetine (Cymbelta) 30 mg 1 Cap HS 6 g furosemide (Rasitol) 40 mg 0.5 Tab ST I/O 33 (Na + =129 mmol/l) 41 參 發 生 率 SSRIs 0.5%-32% 3 SSRIs 13 (3-120 ) 4 18.6 (4-64 ) 5 SSRIs 28 28 ( 85 ) SSRIs 2 肆 機 轉 SSRIs ( ) ( ) SIADH ( ) (glomerular filtration rate) ( ) (atrial natriuretic peptide) ( ) (renin) ADH (osmolality) SSRIs SIADH ( ) 5HT 1 5HT 2 (antidiuretic hormone, ADH) ( ) ADH ( ) ADH ( ) SSRIs (norepinephrine) 1- adrenergic SIADH 4,6 SSRIs cytochrome P450 2D6 4 伍 危 險 因 子 SSRIs SSRIs 60 85% 4,7 臨 30 2 Jun. 30 2014 雜 誌 119 81
臨 ADH (atrial natriuretic peptide) 8 SSRIs SSRIs (30%) (15.1%) (6.7%) (4.1%) 4 60-80% SSRIs 5 陸 臨 症 狀 SIADH < 135 meq/l < 280 mosm/kg > 150 mosm/kg > 20 meq/l < 10 mg/dl < 4 mg/dl 9-10 SIADH SIADH < 130 meq/l 11 柒 SSRI s SIADH SSRIs ( 1000-1500 ml) (NaCl 3% 15-80 ml/hr 1-2 ml/kg/hr) (furosemide 1 mg/kg 20-40 mg q6-12hr) (0.5 meq/l/ h 24 8-12 meq/l) 48-96 2-4 4-8 120-130 meq/l 145 meq/l (central pontine myelinolysis, CPM) (pseudobulbar palsy) urea crystals 30-60 g demeclocycline hydrochloride 600-1200 mg phenytoin sodium 200-300 mg lithium carbonate 600-1200 mg 12 捌 替 代 SSRIs 2 (48-6 ) 4 82 THE JOURNAL OF TAIWAN PHARMACY Vol.30 No.2 Jun. 30 2014
SSRIs Mirtazapine 3 60746 65 5 SSRIs (hazard ratio, HR: 1.52 (95% CI 1.33-1.75)) escitalopram fluoxetine citalopram paroxetine sertraline (tricyclic antidepressants) 2 玖 結 論 13 SSRIs SSRIs SSRIs 65 SSRIs SSRIs (sertraline escitalopram duloxetine) warfarin 14 4 SSRI 臨 Introduction of SSRI Inducing Hyponatremia Tsung-Hsien Chen, Hsing-I Cheng, Shu-Chien Tu, Tang-Chia Chung Department of Pharmacy, Kaohsiung Medical University Hospital Abstract In the last two decades, the prevalence of depression and anxiety disorders has doubled cases in Taiwan. The therapeutic effect of selective serotonin reuptake inhibitors (SSRIs) is better than traditional antidepressants and their side effects are less, thus SSRIs are widely used in the elderly patients. Hyponatremia is one of side effects induced by SSRIs, and the symptom is mainly resulting from inappropriate antidiuretic hormone secretion (SIADH). 30 2 Jun. 30 2014 雜 誌 119 83
臨 It would cause the patient mental confusion, fatigue, low serum sodium concentration, low serum osmolality, high urine osmolality, and high urine sodium concentration and other symptoms. Therefore, this article discussed the possible incidence of mechanisms, risk factors, clinical symptoms, treatment, and the principles of alternative medicine for hyponatremia caused by SSRIs in the elderly male patient. 參考資料 1. 2. 3. 4. 5. 6. 7. 84 The NHS Information Centre Prescribing Support Unit. Prescriptions dispensed in the community, statistics for 1999 to 2009: England. The Health and Social Care Information Centre, 2010. Coupland C, Dhiman P, Morriss R, et al: Antidepressant use and risk of adverse outcomes in older people: population based cohort study. BMJ 2011;343:d4551 p1-15. Jacob S, Spinler SA: Hyponatremia associated with selective serotonin-reuptake inhibitors in older adults. Ann Pharmacother 2006;40(9):1618-22. Liu BA, Mittman N, Knowles SR, Shear NH: Hyponatremia and thesyndrome of inappropriate secretion of antidiuretic hormone associated with the use of selective serotonin reuptake inhibitors: a review of spontaneous reports. Can Med Assoc J 1996;155:519-27. Wilkinson TJ, Begg EJ, Winter AC, Sainsbury R: Incidence and risk factors for hyponatremia following treatment with fluoxetine or paroxetine in elderly people. J Clin Pharmacol 1999;47:211-7. Guay DRP: Hyponatremia associated with selective serotonin reuptake inhibitors. Consult Pharm 2000;15:160-77. Adverse Drug Reactions Advisory Committee. Hypo- THE JOURNAL OF TAIWAN PHARMACY Vol.30 No.2 Jun. 30 2014 8. 9. 10. 11. 12. 13. 14. natremia with SSRIs. Aust Adverse Drug React Bull 2003;22:10. Barclay TS, Lee AJ: Citalopram-associated SIADH. Ann Pharmacother. 2002 Oct;36(10):1558-63. Bourgeois JA, Babine SE, Bahadur N: A case of SIADH and hyponatremia associated with citalopram. Psychosomatics 2002;43:241-2. Hull M, Kottlers M, Braune S: Prolonged coma caused by low sodium and hypo-osmolarity during treatment with citalopram. J Clin Psychopharmacol 2002;22:337-8. Kirby D, Ames D: Hyponatremia and selective serotonin re-uptake inhibitors n elderly patients. Int J Geriatr Psychiatry 2001;16:484-93. Kraft M, Btaiche I, Sacks G, Kudsk K: Treatment of electrolyte disorders in adult patients in the intensive care unit. Am J Health Syst Pharm 2005;62:1663-82. Fu TS, Lee CS, Gunnell D, et al: Changing trends in the prevalence of common mental disorders in Taiwan: a 20-year repeated cross-sectional survey. Lancet 2013;381(9862):235-41. Wallerstedt SM, Gleerup H, Sundstrom A et al: Risk of clinically relevant bleeding in warfarin-treated patientsinfluence of SSRI treatment. Pharmacoepidemiol Drug Saf 2009;18(5):412-416.