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Effect of Fluoxetine on Prothrombin Time

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TO THE EDITOR: Several cases of increased bleeding complications in patients receiving serotonin reuptake inhibiting (SRI) antidepressants and anticoagulant therapy have been reported.^1–3 While some investigators have argued that this side effect may be caused by the action of SRI agents on the serotonergic system of platelets,⁴ the actual mechanism of the interaction remains unknown.

It is possible that SRIs may interfere with the coagulation cascade directly. To investigate this possibility, we examined the effect of increasing concentrations of fluoxetine on prothrombin time (PT) ex vivo in the blood of five normal volunteers. The results (Figure 1) show that fluoxetine does not appear to affect PT in concentration ranges usually achieved in routine clinical use (10–1,000 mg/ml).⁵ At a very high fluoxetine level (100,000 mg/ml), PT is significantly increased above baseline (16.6 ± SD 2.03 vs. 12.3 ± 1.10 sec, t=-8.45, P<0.001). However, this level of fluoxetine also hemolyzes blood cells, a process that could artificially elevate PT.

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Figure 1. Prothrombin time as a function of whole blood concentration of fluoxetine

These data suggest that fluoxetine does not alter PT. However, we did not investigate the effects of its metabolite, norfluoxetine, nor of other SRIs that may also contribute to bleeding problems.

REFERENCES

1. Aranth J, Lindberg C: Bleeding, a side effect of fluoxetine (letter). Am J Psychiatry 1992; 49:412
2. Calhoun JW, Calhoun DD: Prolonged bleeding time in a patient treated with sertraline (letter). Am J Psychiatry 1996; 153:443
3. Skop BP, Brown TM: Potential vascular and bleeding complications of treatment with selective serotonin reuptake inhibitors. Psychosomatics 1996; 37:12–16[Abstract/Free Full Text]
4. Alderman CP, Moritz CK, Ben-Tovim DI: Abnormal platelet aggregation associated with fluoxetine therapy. Ann Pharmachother 1992; 26:1517–1519
5. Koran LM, Cain JW, Dominguez RA, et al: Are fluoxetine plasma levels related to outcome in obsessive-compulsive disorder? Am J Psychiatry 1996; 153:1450–1454[Abstract/Free Full Text]

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