Moderate and high affinity serotonin reuptake inhibitors increase the risk of upper gastrointestinal toxicity

Authors

  • James D. Lewis MD, MSCE,

    Corresponding author
    1. Center for Clinical Epidemiology and Biostatistics, University of Pennsylvania School of Medicine, Philadelphia, PA, USA
    2. Department of Medicine, University of Pennsylvania School of Medicine, Philadelphia, PA, USA
    3. Department of Biostatistics and Epidemiology, University of Pennsylvania School of Medicine, Philadelphia, PA, USA
    • 720 Blockley Hall, 423 Guardian Drive, Philadelphia, PA 19104, USA.
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  • Brian L. Strom MD, MPH,

    1. Center for Clinical Epidemiology and Biostatistics, University of Pennsylvania School of Medicine, Philadelphia, PA, USA
    2. Department of Medicine, University of Pennsylvania School of Medicine, Philadelphia, PA, USA
    3. Department of Biostatistics and Epidemiology, University of Pennsylvania School of Medicine, Philadelphia, PA, USA
    4. Department of Pharmacology, University of Pennsylvania School of Medicine, Philadelphia, PA, USA
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  • A. Russell Localio JD, MPH, MS, MA, PhD,

    1. Center for Clinical Epidemiology and Biostatistics, University of Pennsylvania School of Medicine, Philadelphia, PA, USA
    2. Department of Biostatistics and Epidemiology, University of Pennsylvania School of Medicine, Philadelphia, PA, USA
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  • David C. Metz MD,

    1. Department of Medicine, University of Pennsylvania School of Medicine, Philadelphia, PA, USA
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  • John T. Farrar MD, PhD,

    1. Center for Clinical Epidemiology and Biostatistics, University of Pennsylvania School of Medicine, Philadelphia, PA, USA
    2. Department of Medicine, University of Pennsylvania School of Medicine, Philadelphia, PA, USA
    3. Department of Biostatistics and Epidemiology, University of Pennsylvania School of Medicine, Philadelphia, PA, USA
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  • Robert M. Weinrieb MD,

    1. Department of Psychiatry, University of Pennsylvania School of Medicine, Philadelphia, PA, USA
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  • Lisa Nessel MSS, MLSP,

    1. Center for Clinical Epidemiology and Biostatistics, University of Pennsylvania School of Medicine, Philadelphia, PA, USA
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  • Colleen Brensinger MS,

    1. Center for Clinical Epidemiology and Biostatistics, University of Pennsylvania School of Medicine, Philadelphia, PA, USA
    2. Department of Biostatistics and Epidemiology, University of Pennsylvania School of Medicine, Philadelphia, PA, USA
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  • Stephen E. Kimmel MD, MSCE

    1. Center for Clinical Epidemiology and Biostatistics, University of Pennsylvania School of Medicine, Philadelphia, PA, USA
    2. Department of Medicine, University of Pennsylvania School of Medicine, Philadelphia, PA, USA
    3. Department of Biostatistics and Epidemiology, University of Pennsylvania School of Medicine, Philadelphia, PA, USA
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  • Potential competing interests: Dr Lewis has served as a consultant to Wyeth-Ayerst Laboratories, Pfizer, Bayer, and Merck. He has received research support from GlaxoSmithKline, Pfizer, and Takeda. He has served as an expert on legal actions related to Roche. Dr Kimmel has received research support from Pfizer, Merck, GlaxoSmithKline, and Wyeth-Ayerst Laboratories and has served as a consultant to Pfizer, Bristol-Myers Squibb, Eli Lilly, Centocor, AstraZeneca, and GlaxoSmithKline. Dr Strom has been funded by and served as a consultant to NIH, AHRQ, FDA, and most pharmaceutical manufacturers, including AstraZeneca, Aventis-Pasteur, Bristol Myers Squibb, GlaxoSmithKline, Merck, Pfizer, Schering, and Wyeth. Dr Farrar has been funded by and served as a consultant to Pfizer, Lilly, and Ortho-McNeil. Dr Metz has received grant support, honoraria and/or consulted for Astrazeneca, Wyeth, TAP, Eisai, Altana, GlaxoSmithKline, Santarus, Merck, Pfizer, and Novartis. The other authors have no potential conflicts of interest to report.

Abstract

Objective

Serotonin release from platelets is important for regulating hemostasis. Some prior studies suggest an association between use of selective serotonin reuptake inhibitors and gastrointestinal bleeding and a possible synergistic effect of these medications with non-steroidal anti-inflammatory drugs (NSAIDs). This study examined the effect of medications that inhibit serotonin uptake on upper gastrointestinal toxicity.

Methods

359 case subjects hospitalized for upper gastrointestinal bleeding, perforation, or benign gastric outlet obstruction were recruited from 28 hospitals. 1889 control subjects were recruited by random digit dialing from the same region. Data were collected during structured telephone interviews. Antidepressant medications were characterized according to their affinity for serotonin receptors. Exposure to medications required use on at least 1 day during the week prior to the index date.

Results

Any moderate or high affinity serotonin reuptake inhibitor (MHA-SRI) use was reported by 61 cases (17.1%) and 197 controls (10.4%). After adjusting for potential confounders, MHA-SRI use was associated with a significantly increased odds of hospitalization for upper gastrointestinal toxicity (adjusted OR = 2.0, 95%CI 1.4–3.0). A dose–response relationship in terms of affinity for serotonin uptake receptors was not observed (p = 0.17). No statistical interaction was observed for use of high dose NSAIDs or aspirin concomitantly with MHA-SRIs (p = 0.5). When MHA-SRIs were used concomitantly with high dose NSAIDs, the adjusted odds ratio for the association with upper gastrointestinal toxicity was 3.5 (95%CI 1.9–6.6).

Conclusions

Use of MHA-SRIs is associated with an increased risk of hospitalization for upper gastrointestinal toxicity. Copyright © 2008 John Wiley & Sons, Ltd.

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