Am J Psychiatry：FDA关于大剂量西酞普兰警告受质疑

　　美国一项研究对美国食品与药物管理局（FDA）“西酞普兰＞40 mg/d可能导致心律失常”的警告提出质疑。研究表明，与（1～20） mg/d相比，西酞普兰＞40 mg/d与室性心律失常（校正HR=0.68）、全因死亡（校正HR=0.94）、非心源性死亡（校正HR=0.90）风险较低相关，未发现其增加心源性死亡风险；西酞普兰（21～40） mg/d与室性心律失常风险较低相关（校正HR=0.80）。舍曲林（未受警告的比较药物）队列结果与上述结果相似（图）。论文发表于《美国精神病学杂志》

Evaluation of the FDA Warning Against Prescribing Citalopram at Doses Exceeding 40 mg
Objective 
A recent Food and Drug Administration (FDA) warning cautioned that citalopram dosages exceeding 40 mg/day may cause abnormal heart rhythms, including torsade de pointes. The authors assessed relationships between citalopram use and ventricular arrhythmias and mortality.
Method 
A cohort study was conducted using Veterans Health Administration data between 2004 and 2009 from depressed patients who received a prescription for citalopram (N=618,450) or for sertraline (N=365,898), a comparison medication with no FDA warning. Cox regression models, adjusted for demographic and clinical characteristics, were used to examine associations of antidepressant dosing with ventricular arrhythmia and cardiac, noncardiac, and all-cause mortality.
Results 
Citalopram daily doses >40 mg were associated with lower risks of ventricular arrhythmia (adjusted hazard ratio=0.68, 95% CI=0.61–0.76), all-cause mortality (adjusted hazard ratio=0.94, 95% CI=0.90–0.99), and noncardiac mortality (adjusted hazard ratio=0.90, 95% CI=0.86–0.96) compared with daily doses of 1–20 mg. No increased risks of cardiac mortality were found. Citalopram daily doses of 21–40 mg were associated with lower risks of ventricular arrhythmia (adjusted hazard ratio=0.80, 95% CI=0.74–0.86) compared with dosages of 1–20 mg/day but did not have significantly different risks of any cause of mortality. The sertraline cohort revealed similar findings, except there were no significant associations between daily dose and either all-cause or noncardiac mortality.
Conclusions 
This large study found no elevated risks of ventricular arrhythmia or all-cause, cardiac, or noncardiac mortality associated with citalopram dosages >40 mg/day. Higher dosages were associated with fewer adverse outcomes, and similar findings were observed for a comparison medication, sertraline, not subject to the FDA warning. These results raise questions regarding the continued merit of the FDA warning.