Recent studies have suggested a risk of adverse gastric reactions to selective serotonin-reuptake inhibitors (SSRIs), showing frequent gastrointestinal bleeding in patients taking SSRIs and a markedly increased risk of bleeding with the co-administration of nonsteroidal anti-inflammatory drugs (NSAIDs). Takeuchi et al. investigated the mechanism underlying the ability of SSRIs to exacerbate antral lesions in a refed rat model of NSAID gastrointestinal damage. Multiple NSAIDs and other antidepressants such as fluvoxamine and milnacipran, but not tricyclic/tetracyclic antidepressants, have the same adverse reactions exacerbating antral lesions in the rat model. Exogenous 5-hydroxytryptamine (5-HT) worsened the NSAID-induced antral damage, which was attenuated by the selective 5-HT3 antagonist ondansetron. Indomethacin plus paroxetine significantly decreased mucosal superoxide dismutase activity as well as glutathione. Antisecretory agents and mucosal protective agents prevented antral lesions. These results suggest that SSRIs aggravate NSAID-induced antral lesions via activation of 5HT3 receptors and that the corrosive action may involve acid/pepsin secretion as well as an impaired anti-oxidative system. Therefore, antisecretory and mucosal protective drugs may be useful for the prevention of gastric bleeding induced by the concomitant use of SSRIs and NSAIDs.
See article at J Pharmacol Exp Ther 2011, 338:850–859.
- Copyright © 2011 by The American Society for Pharmacology and Experimental Therapeutics