SSRI And Bleeding Risk In Pregnancy

SSRIs and Bleeding Risk:
Is there increased bleeding risk with pregnancy, GI, CVA?

SSRI Definition:

• Selective serotonin reuptake inhibitor
  
• Inhibition of serotonin uptake in neurons
  
• Allows serotonin to repeatedly stimulate receptors 
  

Bleeding Mechanism:

• Platelet aggregation dysfunction
  
• Blocking uptake of serotonin from blood into platelets
  
• Subsequent impairment in platelet hemostatic response
  
• Decreased platelet aggregability and increased bleeding time
  

Directly increase gastric acidity:
Fluoxetine and sertraline both increase gastric acid secretion - completely eliminated by vagotomy .  Synergistic with aspirin

Potent CYP450 inhibitor:
Subsequently raises blood levels of NSAIDs, antiplatelet drugs

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Bleeding in Pregnancy:
SSRI use 1-2% of all pregnant females

Large Swedish study looking at pregnancy registry, unblinded
n = 500 with SSRI use, 39,000 controls
2.6/2.1 OR elevated risk for PPH/PP anemia
484 mL mean blood loss with SSRI vs 398 mL without SSRI

Clinical Implications:
No overwhelmingly convincing evidence available as of yet
Given bleeding state of pregnancy as well as predilection of SSRIs for bleeding, risk/benefits should be weighed

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GI Bleeding

• 2014 Systematic Review with 15 case-control studies, four cohorts
  
• NNH was 3,177 and 881 in low and high risk groups
  
• Increased risk was 1.66-1.68 in the case control and cohort 
  
• studies
  
• With NSAID use the risk of upper GI bleeding was increased to OR of 4.25
  

Clinical Implications:
Although flawed, pathophysiology and studies combine for reasonable mechanism.  Likely should be avoided if possible.

PPI Therapy:

• Multiple studies - case controls - reporting decreased bleeding with SSRI w/ PPI use de Abajo et al found 9.1 OR SSRI and no PPI, 1.3 WITH PPI
• Targownik hospitalized GI bleeding OR ratio of 0.39 with use of PPI with SSRI
  

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CVA Risks:

• Danish medical registry study, 5833 SSRI users compared to 1:1 number of control
  
• HR 0.77, lower risk of MI or ischemic stroke 
  
• HR 1.89 (CI 0.97-3.66) for bleeding death
  
• HR 1.13 for overall mortality increase
  

Clinical Implications:

• SSRI use likely still advantageous to treat post CVA depression given overall mortality rate HR 1.1
  
• Bleeding risk technically statistically insignificant
  

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Summary:
Do we need to consider bleeding risk when prescribing SSRIs? 

• Keep SSRI in mind when looking at medication list and assessing bleeding risk
  

Greatest risk for SSRI 

• When used in conjunction with NSAIDs
  

Should PPIs be prescribed in conjunction with SSRIs?

• If NSAIDs are frequently used by patient then reasonable to also prescribe PPI
  

Do any recent studies provide strong enough evidence against use for pregnancy, CVA?

• Evidence suggest tendencies towards increased bleeding but only minimally statistically significant, except for combined SSRI and PPI use.