Venlafaxine Joins SSRIs in Risk for Upper GI Bleeding

By John Gever
MADRID, 8 july 2008--Venlafaxine (Effexor) as well as conventional serotonin reuptake inhibitors appears to induce gastrointestinal bleeding in some patients, researchers here said.
In a retrospective case-control study of 1,321 patients with upper gastrointestinal bleeding and 10,000 age- and sex-matched controls, cases were significantly more likely than controls to be current users of selective serotonin reuptake inhibitors (OR 1.6, 95% CI 1.2 to 2.1), the investigators reported in the July issue of Archives of General Psychiatry.
The effect was more pronounced for venlafaxine, a selective norepinephrine reuptake inhibitor (OR 2.9, 95% CI 1.5 to 5.6). reported Francisco J. de Abajo, M.D., Ph.D., M.P.H., of the Spanish Agency for Medicines and Healthcare Products, and Luis A. Garcia-Rodriguez, M.D., M.Sc., of the Spanish Center for Pharmacoepidemiologic Research.
Patients taking serotonin reuptake inhibitors and NSAIDS, without acid-suppressing drugs, were even more heavily over-represented among cases (OR 9.1, 95% CI 4.8 to 17.3).
"The results obtained in the present study support the hypothesis that selective serotonin reuptake inhibitors as a group increase the risk of upper gastrointestinal tract bleeding," the researchers wrote.
Several earlier studies had linked the serotonin reuptake inhibitors to gastrointestinal bleeding, but only a few case reports had implicated venlafaxine, the researchers said.
The use of acid-suppressing drugs such as proton pump inhibitors helped offset the risks associated with antidepressants, though not completely. Drs. de Abajo and Garcia-Rodriguez calculated an odds ratio of 1.2 (95% CI 1.0 to 1.4) for current acid-suppressing drug use among cases versus controls.
Current use of anti-platelet drugs without concomitant acid suppression also appeared to increase the risk of upper gastrointestinal bleeding associated with serotonin reuptake inhibitors, with an odds ratio of 4.7 (95% CI 2.6 to 8.3) for cases versus controls.
Acid suppressants completely offset the extra risks associated with NSAIDs and anti-platelet drugs when those drugs were combined with serotonin reuptake inhibitors, the researchers found.
They calculated odds ratios of 1.1 (95% CI 0.3 to 3.4) for patients taking acid suppressants with NSAIDs as well as antidepressants and 0.8 (95% CI 0.3 to 2.5) for those taking acid suppressants and anti-platelet agents.
Only 15 patients taking venlafaxine or duloxetine (another SNRI) were among the cases. As a result, the researchers were unable to calculate meaningful statistics on the effects of combining them with other agents.
Drug doses or duration of therapy did not appear to influence the risk of bleeding associated with serotonin reuptake inhibitors, they said.
Drs. de Abajo and Garcia-Rodriguez recommended that patients on these antidepressants who are also taking NSAIDs and/or anti-platelet drugs should also take acid suppressants.
Such an approach, they wrote, "would prevent 10 to 20 cases of upper gastrointestinal tract bleeding for every 5,000 patients per year treated concomitantly with serotonin reuptake inhibitors and anti-platelet drugs or with serotonin reuptake inhibitors and NSAIDs."
In fact, their apparent efficacy in this study suggested that acid secretion is part of the mechanism by which serotonin reuptake inhibitors induce gastrointestinal bleeding.
Drs. de Abajo and García-Rodríguez said further research is needed to verify the mechanism.
They acknowledged that the retrospective design was a limitation of the study, as was the possibility that not all drug use was recorded in the database used in the study.
This study was supported by an unrestricted research grant from AstraZeneca for the validation of cases. Dr. Garcia-Rodriguez has received unrestricted research grants from Pfizer, AstraZeneca, and Novartis.

Primary source: Archives of General PsychiatrySource reference:de Abajo F, et al Risk of upper gastrointestinal tract bleeding associated with selective serotonin reuptake inhibitors and venlafaxine therapy: interaction with nonsteroidal anti-inflammatory drugs and effect of acid-suppressing agents" Arch Gen Psych 2008; 65: 795-803.