REVIEW OF: Robbins-Welty GA et al, J Psychosom Res 2026;205:112633
STUDY TYPE: Expert consensus review
SSRIs raise the bleeding risk by depleting serotonin inside of platelets. For most patients, the effect is not dangerous, though women may notice more menstrual bleeding. For those at risk for bleeding disorders, it is a problem, and this consensus statement from the Association of Medicine and Psychiatry offers guidance.
The bottom line on SSRIs: the class roughly doubles bleeding risk in high-risk patients, with odds ratios for upper GI bleeding in the range of 1.6–2.0. But this risk is much smaller for low-risk patients — the number needed to harm for SSRI-associated upper GI bleeding is about 3,177 for low-risk patients and 881 for those also on NSAIDs (common pain medications that also increase bleeding). The bleeding is greatest in the first 30 days. It is not, however, linked to increased death rates.
SNRIs and tricyclics carry similar or slightly lower risk than SSRIs — not low enough to recommend them as a safer swap. Whether higher-potency SSRIs (fluoxetine, paroxetine, sertraline) carry more risk than lower-potency ones (citalopram, escitalopram) is biologically plausible but not consistently demonstrated.
Safer Alternatives
- Bupropion and mirtazapine have the lowest risk of bleeding
- If an SSRI is necessary in a high-risk patient, you can so reduce risk of upper GI bleeds by adding a proton pump inhibitor (eg, esomeprazole and lansoprazole)
Higher Risk Combinations
- SSRIs + NSAIDs (eg ibuprofen, naproxen, celecoxib, aspirin): 4- to 6-fold higher risk (compared to non-users of both)
- SSRIs + Direct Oral Anticoagulants (eg, apixaban (Eliquis), rivaroxaban (Xarelto), and dabigatran (Pradaxa)): 30-70% higher risk
- SSRIs + warfarin: 20-30% increased risk (some also interact with warfarin, raising its levels)
Decision Tool
The group developed the AMP Bleeding Risk Score below — a simple additive tool covering recent major bleeding, anticoagulants, NSAIDs, thrombocytopenia, cirrhosis, and other factors. A score of 3 or higher signals elevated risk and should prompt consideration of bupropion or mirtazapine over an SSRI, or a non-pharmacological approach entirely.
For patients already stable on an SSRI who develop bleeding, the decision to continue versus taper requires weighing psychiatric destabilization risk against bleeding severity; there’s no clean trial data here, so it comes down to clinical judgment and team collaboration. The AMP score is not validated, but it’s a reasonable bedside organizing tool until something better exists.
Practice Implications
Antidepressants are not forever drugs, and SSRIs have medical risks that suggest reconsideration as patients age, especially:
- Bleeding (is AMP Bleeding Risk is 3 or higher?)
- Arrhythmias from QTc (especially with citalopram, though the risk is mainly relevant if cardiac disease, electrolyte abnormalities, or cocacaine/meth use; check score at CredibleMeds)
- Osteoporosis (even higher with trazodone)
- Falls
—Chris Aiken, MD
Director, Psych Partners
Editor in Chief, Carlat Psychiatry Report
Share Your Input in Comments
- Are there other medical risks you are concerned about with SSRIs?
