Is duloxetine (a serotonin-norepinephrine reuptake inhibitor) related to an increased risk of stroke (cerebrovascular accident)?

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Last updated: March 26, 2025View editorial policy

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From the Guidelines

Duloxetine has not been directly linked to causing strokes, though it should be used with caution in patients with a history of cerebrovascular disease. Duloxetine (brand name Cymbalta) is an antidepressant medication that works as a serotonin-norepinephrine reuptake inhibitor (SNRI) and is commonly prescribed for depression, anxiety, diabetic neuropathy, and certain pain conditions. While duloxetine can cause side effects like increased blood pressure in some patients, which theoretically could increase stroke risk, clinical evidence does not suggest it directly causes strokes, as noted in a 2020 clinical practice guideline for the assessment and treatment of children and adolescents with anxiety disorders 1.

Key Considerations

  • The guideline highlights adverse effects of SNRIs, including sustained clinical hypertension, increased blood pressure, and increased pulse, which could theoretically contribute to stroke risk, but does not directly link duloxetine to an increased risk of stroke 1.
  • Patients who have recently had a stroke should discuss with their doctor before starting duloxetine, as the medication might affect blood pressure regulation or interact with blood thinners commonly prescribed after stroke.
  • Additionally, abruptly stopping duloxetine can cause discontinuation symptoms including dizziness and blood pressure changes, so any dosage changes should be done gradually under medical supervision, as emphasized in the guideline 1.
  • If you're concerned about stroke risk while taking duloxetine, consult your healthcare provider who can evaluate your individual risk factors and medical history.

Important Side Effects

  • Duloxetine has been associated with hepatic failure presenting as abdominal pain, hepatomegaly, and elevation of transaminase levels, and should be discontinued and not restarted in patients who develop jaundice or other evidence of clinically significant liver dysfunction 1.
  • Severe skin reactions, including erythema multiforme and Stevens-Johnson syndrome, can occur with duloxetine, and the medication should be discontinued and not restarted at the first appearance of blisters, peeling rash, mucosal erosions, or other signs of hypersensitivity 1.

From the Research

Duloxetine and Stroke Risk

  • The relationship between duloxetine, a serotonin-norepinephrine reuptake inhibitor, and the risk of stroke is complex and has been investigated in several studies 2, 3, 4, 5, 6.
  • A retrospective cohort study found that the rate of acute myocardial infarction, stroke, and out-of-hospital mortality among new users of duloxetine was comparable to that of new users of gabapentin, with an adjusted hazard ratio of 0.98 (95% CI: 0.83,1.16) 2.
  • A medical record-based adverse drug reaction assessment found that long-term use of duloxetine in older adults with cardiovascular comorbidities was associated with cardiovascular-related adverse drug reactions, including peripheral cyanosis, vasoconstriction, atrial fibrillation, and hypertensive episodes 3.
  • A study on the prophylactic effects of duloxetine on post-stroke depression symptoms found that duloxetine spared ischemic stroke patients from both minor and major depression by 16% and promoted rehabilitation, cognitive function, and quality of life 4.
  • Other studies have investigated the effects of duloxetine on blood pressure and pulse rate, finding that supratherapeutic doses of duloxetine can increase blood pressure and pulse rate, but these effects are generally not associated with severe, clinically important adverse events 5, 6.

Key Findings

  • Duloxetine may not increase the risk of stroke compared to other medications, such as gabapentin 2.
  • Long-term use of duloxetine in older adults with cardiovascular comorbidities may be associated with cardiovascular-related adverse drug reactions 3.
  • Duloxetine may have prophylactic effects on post-stroke depression symptoms and promote rehabilitation, cognitive function, and quality of life 4.
  • Supratherapeutic doses of duloxetine can increase blood pressure and pulse rate, but these effects are generally not associated with severe, clinically important adverse events 5, 6.

Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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