摘要：研究背景: 美國食品藥物管理局近期發出一項藥品使用警告，表示使用高劑量的citalopram可能會誘發心律不整，並建議使用該藥物的六十歲以上老年人每日最大劑量為 20毫克。然而兩個美國大型資料庫分析並未顯示高劑量 citalopram會增加心律不整的風險。此外，臨床上對於心律不整之發生風險與選擇性血清素抑制劑類藥品的使用是否有關聯仍不明確，因此須進一步的研究。 研究目的: 比較 1)使用選擇性血清素抑制劑與其他抗憂鬱藥物，2)使用 citalopram與其他選擇性血清素抑制，以及 3)使用 citalopram每日劑量高於 20毫克與低於 20毫克在六十歲以上憂鬱症患者發生心律不整的風險。 研究方法: 本實驗利用 2000至 2011年台灣全民健康保險研究資料庫為資料來源，進行回溯性世代研究。評估對象為 60歲以上、初次使用抗憂鬱症藥物治療的憂鬱症患者，並排除使用多項抗憂鬱藥品為起始治療之患者，或在開始服用抗憂鬱症藥物之前曾經有心律不整診斷之病患。Cox比例風險回歸模型將用於比較選擇性血清素抑制劑或 citalopram的使用者與非使用者間、由第一次處方日期至第一次心律不整診斷之時間。 預期結果: 本實驗結果將對於老年人使用選擇性血清素抑制劑及其誘發心律不整之風險提供更進一步的證據，並將有助於臨床醫師選擇及評估老年族群抗憂鬱藥品的使用。
Abstract: Background: The U.S. Food and Drug Administration (FDA) has recently issued a warning suggesting that a high dose of citalopram may lead to abnormal heart rhythms and recommended the maximum daily dose as 20 mg for patients over 60 years old. However, this is not without controversy. Two claim-based studies found no increased cardiac risks among patients taking high-dose citalopram, and one of the studies even reported a lower risk of ventricular arrhythmia among high-dose citalopram users. In addition, whether the whole therapeutic class of selective serotonin reuptake inhibitors (SSRIs) is associated with an increased cardiac risk remains unclear, and a further investigation on the association between SSRI use and the risk of ventricular arrhythmia is necessary. Objectives: 1) To compare the incidence rate of ventricular arrhythmia between depressive patients over 60 years old receiving SSRIs and other antidepressants, 2) to compare the risk of ventricular arrhythmia between elderly patients who took citalopram and other SSRIs, and 3) to compare the risk of ventricular arrhythmia between elderly patients taking citalopram > 20 mg/day versus patients taking citalopram ≤ 20 mg/day. Method: This will be a retrospective cohort study with a new antidepressant user design. The 2000-2011 National Health Insurance Research Database (NHIRD) will serve as the data source. Patients with at least one inpatient or two outpatient diagnoses of major depressive disorder (ICD-9-CM: 296.2, 296.3) will be included in the initial sample. The date of the first observed antidepressant prescription between January 1st, 2001 and December 31st, 2006 (i.e., the enrollment period) will serve as the index date. To be qualified as new antidepressant users, patients will be required to be free of antidepressant exposure for at least one year prior to the index date. Patients will be excluded if they were ≤ 60 years old on the index date, did not use any antidepressant during the enrollment period, had a diagnosis of cardiac arrhythmias within one year before the index date, used injectable antidepressants at any time during the study period, or were on multiple antidepressants on the index date. SSRI/citalopram exposure will be measured as time-dependent variables. The dependent variable will be the incidence of ventricular arrhythmia, identified by ICD-9-CM codes 427.1, 427.4, 427.41, 427.42, 427.5. All patients will be followed until the occurrence of the first ventricular arrhythmia or five years after the index date, whichever comes first. Cox proportional hazard models with a time-dependent exposure variable will be used to assess the rate of ventricular arrhythmia between SSRI/citalopram users and non-users. Expected Results: Findings from this study will improve our understanding of the cardiac risk associated with SSRI/citalopram use. It will also provide further evidence on the dose effect of citalopram on the risk of ventricular arrhythmia among older patients. By using the NHIRD, the result will be highly generalizable to the elderly population and daily clinical practice in Taiwan. It will also assist physicians to make better clinical decisions when treating older patients with depression. Results from this study will be turned into publications on peer-review journals and international conferences.
