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Articles   |    
Short-Term Use of Serotonin Reuptake Inhibitors and Risk of Upper Gastrointestinal Bleeding
Yen-Po Wang, M.D.; Yung-Tai Chen, M.D.; Chia-Fen Tsai, M.D.; Szu-Yuan Li, M.D.; Jiing-Chyuan Luo, M.D.; Shuu- Jiun Wang, M.D.; Chao-Hsiun Tang, Ph.D.; Chia-Jen Liu, M.D.; Han-Chieh Lin, M.D.; Fa-Yauh Lee, M.D.; Full-Young Chang, M.D.; Ching-Liang Lu, M.D.
Am J Psychiatry 2014;171:54-61. doi:10.1176/appi.ajp.2013.12111467
View Author and Article Information

Drs. Yen-Po Wang and Yung-Tai Chen contributed equally to this article.

The authors report no financial relationships with commercial interests.

From the Division of Gastroenterology, Division of Nephrology, Division of Hematology and Oncology, Department of Internal Medicine, Department of Psychiatry, and Neurological Institute, Taipei Veterans General Hospital, Taipei, Taiwan; Department of Medicine, Taipei City Hospital Heping Fuyou Branch, Taipei; the Institute of Brain Science, Institute of Clinical Medicine, Department of Medicine, and School of Medicine, National Yang-Ming University, Taipei; and the School of Health Care Administration, Taipei Medical University, Taipei.

Address correspondence to Dr. Ching-Liang Lu (cllu@vghtpe.gov.tw).

Copyright © 2014 by the American Psychiatric Association

Received November 25, 2012; Revised April 30, 2013; Accepted June 24, 2013.

Abstract

Objective  The association between selective serotonin receptor inhibitors (SSRIs) and risk of upper gastrointestinal bleeding remains controversial. Previous studies have generally evaluated the issue for approximately 3 months, even though the SSRI-mediated inhibition of platelet serotonin concentrations occurs within 7–14 days. The authors explored the risk of upper gastrointestinal bleeding after short-term SSRI exposure by a case-crossover design.

Method  The records of psychiatric inpatients with upper gastrointestinal bleeding were retrieved from the Taiwan National Health Insurance Database (1998−2009). Rates of antidepressant use were compared for case and control periods with time windows of 7, 14, and 28 days. The adjusted self-matched odds ratios from a conditional logistic regression model were used to determine the association between SSRI use and upper gastrointestinal bleeding.

Results  A total of 5,377 patients with upper gastrointestinal bleeding were enrolled. The adjusted odds ratio for the risk of upper gastrointestinal bleeding after SSRI exposure was 1.67 (95% CI=1.23–2.26) for the 7-day window, 1.84 (95% CI=1.42–2.40) for the 14-day window, and 1.67 (95% CI=1.34–2.08) for the 28-day window. SSRIs with high and intermediate, but not low, affinity for serotonin transporter were associated with upper gastrointestinal bleeding. An elevated risk of upper gastrointestinal bleeding after SSRI exposure was seen in male but not female patients.

Conclusions  Short-term SSRI use (7–28 days) is significantly associated with upper gastrointestinal bleeding. Gender differences may exist in the relationship between SSRI use and upper gastrointestinal bleeding. Physicians should carefully monitor signs of upper gastrointestinal bleeding even after short-term exposure to SSRIs, as is done with nonsteroidal anti-inflammatory drugs and aspirin.

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FIGURE 1. Illustration of Case-Crossover Design to Evaluate the Risk of Upper Gastrointestinal Bleeding After Short-Term SSRI Exposurea

a Index date=date of upper gastrointestinal bleeding.

FIGURE 2. Risk of Upper Gastrointestinal Bleeding After Short-Term Use of Selective Serotonin Reuptake Inhibitors (N=5,377)a

a Odds ratios were calculated for each of the three time windows and adjusted according to the use of proton pump inhibitors, histamine-2 receptor blockers, nonsteroidal anti-inflammatory drugs, clopidogrel, systemic corticosteroids, vitamin K antagonists, and aspirin. Results were significant at p<0.001 for all three time windows. Error bars indicate 95% confidence intervals.

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TABLE 1.Demographic and Clinical Characteristics of Patients With Upper Gastrointestinal Bleeding (N=5,377)a
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a SSRI=selective serotonin reuptake inhibitor; IQR=interquartile range.

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b Distribution of scores on the Charlson comorbidity index: 0–2, 41.5%; ≥3, 58.5%.

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TABLE 2.Risk of Upper Gastrointestinal Bleeding Associated With Current Use of Antidepressantsa
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a SSRIs=selective serotonin reuptake inhibitors; SNRIs=serotonin-norepinephrine reuptake inhibitors; MAO=monoamine oxidase. In the case-crossover design, each patient serves as his or her own control.

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b Adjusted for the use of proton pump inhibitors, histamine-2 receptor blockers, nonsteroidal anti-inflammatory drugs, clopidogrel, systemic corticosteroids, vitamin K antagonists, and aspirin.

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TABLE 3.Risk of Upper Gastrointestinal Bleeding With Current Use of Antidepressants for 14-Day Windowa
Table Footer Note

a SSRIs=selective serotonin reuptake inhibitors; SNRIs=serotonin-norepinephrine reuptake inhibitors; MAO=monoamine oxidase. In the case-crossover design, each patient serves as his or her own control. Some patients were taking more than one kind of drug, so totals are not equal to the sum of the individual drugs.

Table Footer Note

b Adjusted for the use of proton pump inhibitors, histamine-2 receptor blockers, nonsteroidal anti-inflammatory drugs, clopidogrel, systemic corticosteroids, vitamin K antagonists, and aspirin.

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c Subsamples too small to calculate odds ratios.

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TABLE 4.Risk of Upper Gastrointestinal Bleeding Interactions With Concurrent Use of SSRIs, NSAIDs, and Aspirina
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a SSRIs=selective serotonin reuptake inhibitors; NSAIDs=nonsteroidal anti-inflammatory drugs.

Table Footer Note

b Adjusted for the use of proton pump inhibitors, histamine-2 receptor blockers, clopidogrel, systemic corticosteroids, and vitamin K antagonists.

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