What antidepressants can be taken with Eliquis (apixaban)?

Antidepressants That Can Be Safely Taken with Eliquis (Apixaban)

For patients taking Eliquis (apixaban), the safest antidepressant options are those with minimal serotonin reuptake inhibition such as mirtazapine or bupropion, as they have the lowest risk of increasing bleeding complications.

Understanding the Risk

Eliquis (apixaban) is an anticoagulant that already carries an inherent bleeding risk. When combined with certain antidepressants, particularly those with strong serotonin reuptake inhibition, this risk can be significantly increased:

• Meta-analysis evidence shows that serotonin reuptake inhibitor (SRI) antidepressants increase the risk of bleeding by 1.16 to 2.36-fold 1
• Among individuals receiving anticoagulants, SRI users experienced a 39% higher risk of major bleeding compared to non-SRI users (OR 1.39,95% CI 1.23-1.58) 2

Recommended Antidepressant Options with Eliquis

First-Line Options (Lowest Bleeding Risk)

• Mirtazapine:

  • Has minimal serotonin reuptake inhibition 1
  • Additional benefit: Promotes sleep, appetite, and weight gain 3
  • Starting dose: 7.5 mg at bedtime; maximum: 30 mg at bedtime 3

• Bupropion:

  • Has minimal serotonin reuptake inhibition 1
  • Starting dose: 37.5 mg every morning, then increase by 37.5 mg every 3 days
  • Maximum dose: 150 mg twice daily 3
  • Note: Should not be used in patients with seizure disorders; may cause insomnia if second dose taken after 3 pm 3

Second-Line Options (Moderate Risk)

If first-line options are ineffective or contraindicated, consider antidepressants with moderate serotonin reuptake inhibition:

• Venlafaxine:

  • Has moderate serotonin reuptake inhibition
  • Effective for both depression and anxiety symptoms 3

• Desvenlafaxine:

  • Metabolite of venlafaxine with similar efficacy profile
  • May have fewer drug interactions 4

Antidepressants to Use with Caution

• Sertraline: Has less effect on metabolism of other medications compared to other SSRIs 3, but still increases bleeding risk
• Citalopram/Escitalopram: Moderate serotonin reuptake inhibition with fewer drug interactions than other SSRIs 5

Antidepressants to Avoid

• Paroxetine and Fluoxetine: Highest degree of serotonin reuptake inhibition and most frequently associated with abnormal bleeding 6
• Tricyclic antidepressants: Associated with increased risk of cardiac arrest (OR = 1.69) 3

Risk Mitigation Strategies

1. Monitor for Bleeding Signs:

   • Unusual bruising
   • Prolonged bleeding from minor cuts
   • Nosebleeds
   • Blood in urine or stool
   • Severe headache (potential sign of intracranial hemorrhage)

2. Consider Gastroprotection:

   • Acid-reducing medications may mitigate risk of gastrointestinal bleeds in patients taking both SRIs and NSAIDs 1
   • Avoid concurrent use of NSAIDs and aspirin when possible, as this creates a synergistic bleeding risk (OR range 3.17-10.9) 1

3. Laboratory Monitoring:

   • Consider more frequent INR monitoring when initiating or changing antidepressant therapy
   • Monitor for signs of platelet dysfunction or coagulation disorders if bleeding occurs 6

Special Considerations

• Elderly patients are at higher risk for bleeding complications and may require lower starting doses of antidepressants 3
• Patients with a history of GI bleeding should be particularly cautious with any serotonergic antidepressant
• If depression is severe and an SSRI is deemed necessary despite the bleeding risk, consider adding gastroprotection with a proton pump inhibitor

Algorithm for Antidepressant Selection with Eliquis

1. Assess depression severity and specific symptoms (sleep, anxiety, etc.)
2. Evaluate patient-specific bleeding risk factors (age, history of bleeding, concurrent medications)
3. For patients with low-moderate depression severity: Start with mirtazapine or bupropion
4. For patients with severe depression or non-response to first-line agents: Consider venlafaxine or desvenlafaxine with close monitoring
5. Avoid high serotonin reuptake inhibitors (paroxetine, fluoxetine) in all patients taking Eliquis

By carefully selecting antidepressants with lower serotonin reuptake inhibition and implementing appropriate monitoring strategies, the risk of bleeding complications can be minimized while effectively treating depression in patients taking Eliquis.