Can treatment with antidepressants increase the risk for gastrointestinal bleeding?/nA 25-year-old
Fråga: Can treatment with antidepressants increase the risk for gastrointestinal bleeding?
A 25-year-old woman with personality disorder, depressive symptoms and anxiety received blood transfusion because of a gastrointestinal bleeding nine months ago. Recently a small GI-bleeding reappeared. The patient is currently treated at the department of gastroenterology. Antidepressant therapy is now considered.
Sammanfattning: Based on several case reports and a population study selective serotonin reuptake inhibitors may increase the risk of bleeding disorders compared to other antidepressants. However, mild bleeding disorders such as purpura, intermenstrual bleeding, epistaxis seem to be more frequent compared to serious conditions such as gastrointestinal and intracranial haemorrhage. The present patient should be adequately monitored during treatment with SSRI´s. In case of a new bleeding reaction withdrawal of the drug is recommended. An alternative treatment with tricyclic antidepressants or noradrenergic substances such as reboxetin may also be considered.
Svar: Case reports have suggested an association between antidepressants and bleeding disorders. Both selective serotonin reuptake inhibitors (SSRI) such as fluoxetine and tricyclic antidepressants such as clomipramine are mentioned in connection with prolonged bleeding time and an increased risk of bruises (1-3). The Swedish Medical Product Agency has received 19 reports of haematological side-effects such as ecchymoses (16 reports) and epistaxis (3 reports) associated with SSRI-treatment. The onset of symptoms was within five weeks of the start of the treatment in most cases. In all cases the symptoms were reversible upon withdrawal of the drug. A few cases had a positive rechallenge ie when treatment was reintroduced the symptoms reappeared. The WHO side-effect database contains a total of 3500 reports related to SSRI. These includes about 1000 cases of purpura, 250 cases of intermenstrual bleeding, 140 cases of epistaxis, 120 cases of vaginal bleeding, 170 cases of GI-bleeding, 60 cases of hematoma, and 34 cases of cerebral bleeding (4).
The mechanism by which SSRI might increase the risk for GI-bleeding is not known, but it has been suggested that the effect on haemostasis is a class effect of SSRI and may be due to
the inhibition of serotonin reuptake in platelets. This may cause a depletion of stored serotonin and thereby a disturbance in platelet function. Thus, platelet aggregation followed by bleeding may be the end result (4).
High doses of a selective serotonin reuptake inhibitor have been mentioned as a risk factor for haemorrhagic side effects. However, plasma concentrations were not monitored in these patients. Further, metabolic defects in enzymes responsible in drug metabolism were not investigated (4).
Recently a population based case-control study over four years was published (5). One thousand and six hundred fifty-one cases of upper GI-bleeding and 248 cases of gastric ulcer with perforation were compared with 10000 controls. Three percent of cases had taken SSRI compared with one percent of controls, giving an adjusted rate ratio of three. Incidence of one case per 8000 prescriptions was estimated. No association was found with antidepressants lacking an inhibitory effect on serotonin. No patient treated with SSRI´s developed a gastric ulcer. Concomitant treatment with NSAID´s increased the risk of upper GI-bleeding about fifteen times (5). However, an editorial criticises the database used in this study since over the counter drugs eg antihistamines, aspirin and ibuprofen, which may confound estimates of risk were not considered (6). According to this editorial, selectivity characteristics for serotonin transporter over norepinephrine transporter is associated with a higher risk of upper GI-bleeding. The author points out that selective serotonin reuptake inhibitors, clomipramine, imipramine and venlafaxine are drugs with a high 5-HT selectivity (6).