Is bleeding a known adverse effect of venlafaxine?/nBackground: A 44-year-old woman has been treate

Fråga: Is bleeding a known adverse effect of venlafaxine? Background: A 44-year-old woman has been treated with venlafaxine for about eight months. Since the initial dose of 75 mg/day did not sufficiently ameliorate the symptoms of depression the dose was increased to 225 mg/day three weeks ago. Shortly thereafter, problems with easy bruising became apparent. Even minor mosquito bites resulted in hemorrhagic blisters. The same phenomenon was observed two years ago when the patient was under treatment with Fontex (fluoxetine), 50 mg/day. The patient had a normal PK (prothrombin complex) value and the symptoms disappeared after drug withdrawal. The patient had not done well on TCA because of side effects. What antidepressant(s) can be recommended?

Sammanfattning: Limited data implies that venlafaxine might cause bleeding tendencies. Since this effect is probably dose-dependent, a lower dose might be tried. Alternatively, an antidepressant that does not affect serotonin uptake, eg mianserin or mirtazapine can be tried.

Svar: The available literature concerning increased bleeding risk in patients treated with venlafaxine is very limited. Two case reports were located. A 19-year-old woman developed easy and spontaneous bruising one week after initiating venlafaxine 50 mg bid (1). The symptoms resolved 10 days after drug withdrawal. Coagulation parameters were normal. However, bleeding time was not measured. A venlafaxine-mediated change in platelet serotonin was suggested as a possible explanation (1). However, since venlafaxine was started only one week after cessation of sertraline, a pharmacokinetic interaction between the two drugs can not be ruled as a cause of the increased bleeding diathesis observed. The other case report concerned a 47-year-old woman with insulin dependent diabetes mellitus and hypothyroidism who developed ecchymoses two and a half months after initiating venlafaxine therapy (2). On admisssion she was found to have elevated partial thromboplastin time along with a high antihemophilic factor VIII, C antibody. Her platelet count was normal. This unusual clotting defect, apparently mediated via autoimmune mechanisms resolved upon discontinuation of venlafaxine and treatment with desmopressin, intravenous immunoglobin and cyclophosphamide.

One case of hematoma and one of cerebral hemorrhage, possibly caused by venlafaxine were reported to SADRAC (3). Venlafaxine was judged as the probable cause of multiple hematomas and hypertension in another reported case (3). The WHO database on adverse drug effects (4) contains a number of case reports of hemostasis-related adverse effects in patients treated with venlafaxine (3 cases of increased bleeding time, 7 of coagulation disorder, 6 of epistaxis, 2 of abnormal platelets, 5 of gingival bleeding, 4 of hematoma, 3 of hemorrhage, 112 of purpura, 28 of thrombocytopenia). These cases, however, are not assessed with regards to causality. The manufacturer has not received any reports on venlafaxine associated bleeding apart from the above mentioned case (7).

Bleeding reactions associated with the use of different SSRI have been reported and the Swedish Medical Products Agency has urged physicians to be aware of and report these adverse effects (5). Although the underlying mechanism has not been elucidated, inhibition of serotonin uptake by thrombocytes appears plausible (5). Such an inhibition would deplete serotonin stores in thrombocytes and affect their aggregation. Since venlafaxine is a potent serotonin re-uptake inhibitor (6) similar effects on thrombocyte function may not be surprising. The scarce documentation might be at least in part be due to the fact that venlafaxine is relatively new on the market.

Antidepressants that do not affect serotonin uptake, eg mianserin or mirtazapine have not been associated with increased bleeding risk.

We recommend this case be reported to SADRAC.