- Email: [email protected]
Increased Use of Selective Serotonin Reuptake Inhibitors in Patients Admitted With Acute Gastrointestinal Hemorrhage: Preliminary Observations
Abstracts
912.01 Effect of Repeated Bolus Injection, Low or High Dose Continuous Infusion of Omeprazole on Intragastric pH in Patients With Bleeding Peptic Ulcer v a Dose-Titration Study Philip Wai Y., Simon Kin Hung Wong, Justin Chi Yuen Wu, Man Yee Yung, Wilfred Mui, Enders Kwok Wai Ng, James Yun Wong Lau, Joseph Sung Aim: From our previous study, we have shown that the adjunctive use of high dose omeprazole infusion reduced the rate of recurrent bleeding after endoscopic hemostasis for bleeding peptic ulcers. The appropriate dose of omeprazole to achieve optimal pH profile for clot stability is unknown. The aim of this study is to define the gastric acid suppression profile among various regimens of adjunctive omeprazole. Patients and Method: We included patients that presented with bleeding peptic ulcers and had endoscopic stigmata of either red dot or clean base that do not required endoscopic treatment. We excluded those that received regular antisecretory medications, NSAID/aspirin users, previous gastric surgery and moribund patients. All patients were randomly assigned to receive various dosage protocol of proton pump inhibitor for 24 hours, including 1. Omeprazole 80 mg bolus, then 8 mg/hr infusion (192 mg/d); 2. Omeprazole 80 mg bolus, then 4 mg/hr infusion (96 mg/d); or 3. Omeprazole intravenous 40 mg bolus 6 hourly (160 mg/d). We measured the 24 hour fasting gastric pH with the electrode positioned at 10 cm below the gastroesophageal junction. We collected the median pH, % time pH O 4 and % time pH O 6 at intervals of 1 hour, 4 hour, 12 hour and 24 hours after the start of therapy. We also analyzed the time needed to attain pH O 4 and pH O 6. Results: We included 30 patients with bleeding peptic ulcers that had endoscopic stigmata of either red dot or clean base. 11 patients received omeprazole 40 mg every 6 hourly, 10 patients received omeprazole 4mg/hr and 9 patients received omeprazole 8 mg/hr. The three groups were comparable in terms of age, body weight, ulcer size, initial blood pressure and hemoglobin level. There was no difference in the % time pH O 4 or 6 at 1, 4, 12 and 24 hours between the three groups. However, we found that those patients receiving omeprazole 8 mg/hr could reach pH O 4 in a significantly shorter time (Kruskal-Wallis test p Z 0.04) (Figure 1). Conclusion: Patients receiving a regime of high dose omeprazole infusion at 8mg/hr attained an intragastric pH profile of more than 4 in a significantly shorter period of time. A high dose regimen may be more effective in prevention of early recurrent rebleeding by early clot stabilization.
matched R1:1 with patients admitted on the same date with a nonbleeding diagnosis. Subjects were excluded if there was a history of liver disease, portal hypertension or primary hematologic or coagulation disorder. Use of SSRI, NSAID, ASA, plavix, coumadin and lovenox was determined. In this preliminary analysis, odds ratios (95% CI) for use of these agents were determined in patients with GIB compared with controls. Results: 917 cases have been registered to date and include 417 bleeders and 500 controls. SSRI use was 12% in controls and 17% in bleeders (OR Z 1.5{1.02-2.14}; p Z 0.04). Use of NSAID/COX2 agents was 13% in controls and 17% in bleeders (OR Z 1.4{0.99-2.06}; p Z 0.06). Use of ASA/plavix was 30% in controls and 41% in bleeders (OR Z 1.6{1.2-2.07}; p Z 0.001). Use of coumadin/lovenox was 16% in controls and 24% in bleeders (OR Z 1.3{0.93-1.93}; p Z 0.12). PPI/H2RA use was 23% in controls and 34% in bleeders (OR Z 1.7; {1.292.32}; p Z 0.003). Patients admitted with bleeding were significantly more likely to be using more than one medication associated with increased risk of GIB (c2 Z 22; p Z 0.0002). Sample size in this preliminary analysis is insufficient to calculate drug interactions or generate a predictive model with statistical certainty. Conclusions: This preliminary analysis confirms the association of SSRI use with GIB. Increased SSRI use in the bleeding population is comparable to increased NSAID use. The modest increase in OR for drugs studied may reflect sample size, a more ill control population than previously studied and the high prevalence of SSRI use in our population. Continued enrollment will improve statistical power allowing better definition of risks and interactions between classes. Sponsored by a grant from TAP Pharmaceuticals
Figure 1. Dose of PPI against time to attain pH > 4
912.03 Selective Serotonin Re-Uptake Inhibitors (SSRIS) Aggravate Antral Ulcers Induced by Indomethacin in Rat Stomachs Koji Takeuchi, Akiko Tanaka, Yuka Takahira, Masaki Taniguchi
912.02 Increased Use of Selective Serotonin Reuptake Inhibitors in Patients Admitted With Acute Gastrointestinal Hemorrhage: Preliminary Observations Michael P. Jones, Sarah Wessinger, Michael Williams, Lillian Choi, Lisa Sharp, Michael Crowell, Ali Keshavarzian Introduction: Selective serotonin reuptake inhibitors (SSRIs) can adversely affect platelet function and cause abnormal hemostasis. Case series have suggested increased risk of bleeding disorders and hemorrhage. Several studies have suggested an approximate three-fold increased risk of gastrointestinal bleeding (GIB) in persons taking SSRIs compared with healthy controls. We evaluated use of SSRIs along with other agents known to increase risk of GIB in patients admitted with acute GIB compared with hospitalized controls. Our preliminary observations are reported here. Methods: Retrospective, case control study on inpatients admitted with acute GIB between 6/03 and 12/03. Cases were all age and sex
AB86 GASTROINTESTINAL ENDOSCOPY Volume 61, No. 5 : 2005
Background/Aim: Recent clinical studies suggested a risk of gastric adverse reactions on the concomitant use of selective serotonin re-uptake inhibitors (SSRIs) with nonsteroidal anti-inflammatory drugs (NSAIDs). However, little information has only been available concerning the adverse effect of SSRIs in the gastrointestinal tract as well as the underlying mechanism of this action. In the present study, we used indomethacin as a conventional NSAID and investigated the adverse effect of SSRIs on gastric antral and corpus lesions as well as intestinal lesions induced by indomethacin in rats. Methods: Male SD rats were used. Gastric corpus or intestinal lesions were induced in fasted or fed rats, respectively, by SC injection of indomethacin (30 mg/kg or 10 mg/kg), and the animals were killed 4 or 24 h after the administration. For induction of antral ulcers, the rats were fed chow for 1 h after 24 h fasting, then given indomethacin (30 mg/kg) SC 1 h after refeeding, and they were killed 6 h later. SSRIs or other drugs were given PO 30 min before indomethacin. Results: Indomethacin caused gastric corpus lesions in fasted rats, intestinal lesions in fed rats, and antral ulcers in fasted/re-fed rats. Paroxetine, one of the SSRIs, dose-dependently suppressed indomethacin-induced gastric corpus and intestinal lesions. However, this agent markedly aggravated the severity of antral ulcers in response to indomethacin, despite provoking by itself no damage; the original ulcers induced by indomethacin were mostly nonhemorrhagic while they became hemorrhagic by co-administration of paroxetine. Similar results were obtained with another SSRI fluvoxamine, but not the tricyclic antidepressant imipramine or the tetracyclic antidepressant maprotiline. Exogenous serotonin (5-HT) but not mosapride (a 5-HT4 agonist) also worsened indomethacin-induced antral ulcers, while the worsening effect of paroxetine was attenuated by methysergide, the nonselective 5-HT antagonist. It was also found that antral ulcers induced by indomethacin plus paroxetine was significantly prevented by the antipeptic agent pepstatin as well as the anticholinergic agent atropine. Conclusion: These results suggest that SSRIs exert a harmful influence on the gastric mucosa when given with NSAID, resulting in hemorrhagic antral ulcers, and endogenous 5-HT as well as pepsin may be involved in the aggravating action of SSRIs. Thus, a caution should be paid for the use of SSRIs in patients taken NSAIDs.
www.mosby.com/gie
912.01 Effect of Repeated Bolus Injection, Low or High Dose Continuous Infusion of Omeprazole on Intragastric pH in Patients With Bleeding Peptic Ulcer v a Dose-Titration Study Philip Wai Y., Simon Kin Hung Wong, Justin Chi Yuen Wu, Man Yee Yung, Wilfred Mui, Enders Kwok Wai Ng, James Yun Wong Lau, Joseph Sung Aim: From our previous study, we have shown that the adjunctive use of high dose omeprazole infusion reduced the rate of recurrent bleeding after endoscopic hemostasis for bleeding peptic ulcers. The appropriate dose of omeprazole to achieve optimal pH profile for clot stability is unknown. The aim of this study is to define the gastric acid suppression profile among various regimens of adjunctive omeprazole. Patients and Method: We included patients that presented with bleeding peptic ulcers and had endoscopic stigmata of either red dot or clean base that do not required endoscopic treatment. We excluded those that received regular antisecretory medications, NSAID/aspirin users, previous gastric surgery and moribund patients. All patients were randomly assigned to receive various dosage protocol of proton pump inhibitor for 24 hours, including 1. Omeprazole 80 mg bolus, then 8 mg/hr infusion (192 mg/d); 2. Omeprazole 80 mg bolus, then 4 mg/hr infusion (96 mg/d); or 3. Omeprazole intravenous 40 mg bolus 6 hourly (160 mg/d). We measured the 24 hour fasting gastric pH with the electrode positioned at 10 cm below the gastroesophageal junction. We collected the median pH, % time pH O 4 and % time pH O 6 at intervals of 1 hour, 4 hour, 12 hour and 24 hours after the start of therapy. We also analyzed the time needed to attain pH O 4 and pH O 6. Results: We included 30 patients with bleeding peptic ulcers that had endoscopic stigmata of either red dot or clean base. 11 patients received omeprazole 40 mg every 6 hourly, 10 patients received omeprazole 4mg/hr and 9 patients received omeprazole 8 mg/hr. The three groups were comparable in terms of age, body weight, ulcer size, initial blood pressure and hemoglobin level. There was no difference in the % time pH O 4 or 6 at 1, 4, 12 and 24 hours between the three groups. However, we found that those patients receiving omeprazole 8 mg/hr could reach pH O 4 in a significantly shorter time (Kruskal-Wallis test p Z 0.04) (Figure 1). Conclusion: Patients receiving a regime of high dose omeprazole infusion at 8mg/hr attained an intragastric pH profile of more than 4 in a significantly shorter period of time. A high dose regimen may be more effective in prevention of early recurrent rebleeding by early clot stabilization.
matched R1:1 with patients admitted on the same date with a nonbleeding diagnosis. Subjects were excluded if there was a history of liver disease, portal hypertension or primary hematologic or coagulation disorder. Use of SSRI, NSAID, ASA, plavix, coumadin and lovenox was determined. In this preliminary analysis, odds ratios (95% CI) for use of these agents were determined in patients with GIB compared with controls. Results: 917 cases have been registered to date and include 417 bleeders and 500 controls. SSRI use was 12% in controls and 17% in bleeders (OR Z 1.5{1.02-2.14}; p Z 0.04). Use of NSAID/COX2 agents was 13% in controls and 17% in bleeders (OR Z 1.4{0.99-2.06}; p Z 0.06). Use of ASA/plavix was 30% in controls and 41% in bleeders (OR Z 1.6{1.2-2.07}; p Z 0.001). Use of coumadin/lovenox was 16% in controls and 24% in bleeders (OR Z 1.3{0.93-1.93}; p Z 0.12). PPI/H2RA use was 23% in controls and 34% in bleeders (OR Z 1.7; {1.292.32}; p Z 0.003). Patients admitted with bleeding were significantly more likely to be using more than one medication associated with increased risk of GIB (c2 Z 22; p Z 0.0002). Sample size in this preliminary analysis is insufficient to calculate drug interactions or generate a predictive model with statistical certainty. Conclusions: This preliminary analysis confirms the association of SSRI use with GIB. Increased SSRI use in the bleeding population is comparable to increased NSAID use. The modest increase in OR for drugs studied may reflect sample size, a more ill control population than previously studied and the high prevalence of SSRI use in our population. Continued enrollment will improve statistical power allowing better definition of risks and interactions between classes. Sponsored by a grant from TAP Pharmaceuticals
Figure 1. Dose of PPI against time to attain pH > 4
912.03 Selective Serotonin Re-Uptake Inhibitors (SSRIS) Aggravate Antral Ulcers Induced by Indomethacin in Rat Stomachs Koji Takeuchi, Akiko Tanaka, Yuka Takahira, Masaki Taniguchi
912.02 Increased Use of Selective Serotonin Reuptake Inhibitors in Patients Admitted With Acute Gastrointestinal Hemorrhage: Preliminary Observations Michael P. Jones, Sarah Wessinger, Michael Williams, Lillian Choi, Lisa Sharp, Michael Crowell, Ali Keshavarzian Introduction: Selective serotonin reuptake inhibitors (SSRIs) can adversely affect platelet function and cause abnormal hemostasis. Case series have suggested increased risk of bleeding disorders and hemorrhage. Several studies have suggested an approximate three-fold increased risk of gastrointestinal bleeding (GIB) in persons taking SSRIs compared with healthy controls. We evaluated use of SSRIs along with other agents known to increase risk of GIB in patients admitted with acute GIB compared with hospitalized controls. Our preliminary observations are reported here. Methods: Retrospective, case control study on inpatients admitted with acute GIB between 6/03 and 12/03. Cases were all age and sex
AB86 GASTROINTESTINAL ENDOSCOPY Volume 61, No. 5 : 2005
Background/Aim: Recent clinical studies suggested a risk of gastric adverse reactions on the concomitant use of selective serotonin re-uptake inhibitors (SSRIs) with nonsteroidal anti-inflammatory drugs (NSAIDs). However, little information has only been available concerning the adverse effect of SSRIs in the gastrointestinal tract as well as the underlying mechanism of this action. In the present study, we used indomethacin as a conventional NSAID and investigated the adverse effect of SSRIs on gastric antral and corpus lesions as well as intestinal lesions induced by indomethacin in rats. Methods: Male SD rats were used. Gastric corpus or intestinal lesions were induced in fasted or fed rats, respectively, by SC injection of indomethacin (30 mg/kg or 10 mg/kg), and the animals were killed 4 or 24 h after the administration. For induction of antral ulcers, the rats were fed chow for 1 h after 24 h fasting, then given indomethacin (30 mg/kg) SC 1 h after refeeding, and they were killed 6 h later. SSRIs or other drugs were given PO 30 min before indomethacin. Results: Indomethacin caused gastric corpus lesions in fasted rats, intestinal lesions in fed rats, and antral ulcers in fasted/re-fed rats. Paroxetine, one of the SSRIs, dose-dependently suppressed indomethacin-induced gastric corpus and intestinal lesions. However, this agent markedly aggravated the severity of antral ulcers in response to indomethacin, despite provoking by itself no damage; the original ulcers induced by indomethacin were mostly nonhemorrhagic while they became hemorrhagic by co-administration of paroxetine. Similar results were obtained with another SSRI fluvoxamine, but not the tricyclic antidepressant imipramine or the tetracyclic antidepressant maprotiline. Exogenous serotonin (5-HT) but not mosapride (a 5-HT4 agonist) also worsened indomethacin-induced antral ulcers, while the worsening effect of paroxetine was attenuated by methysergide, the nonselective 5-HT antagonist. It was also found that antral ulcers induced by indomethacin plus paroxetine was significantly prevented by the antipeptic agent pepstatin as well as the anticholinergic agent atropine. Conclusion: These results suggest that SSRIs exert a harmful influence on the gastric mucosa when given with NSAID, resulting in hemorrhagic antral ulcers, and endogenous 5-HT as well as pepsin may be involved in the aggravating action of SSRIs. Thus, a caution should be paid for the use of SSRIs in patients taken NSAIDs.
www.mosby.com/gie