- Email: [email protected]
Amitriptylin for the treatment of IBS
April 2000
AGAA617
3168
3170
A PLACEBO-CONTROLLED, DOUBLE-BLIND TRIAL OF ACUPUNCTURE IN THE TREATMENT OF IRRITABLE BOWEL SYNDROME( ras i Catherine Lowe, William T. Depew, Stephen 1. Vanner, Acad Univ, Kingston, ON, Canada.
ROLE OF 5-HT 3 RECEPTORS IN RADIATION-INDUCED ALTERATIONS OF COLONIC MOTILITY AND FLUID ABSORP· TION IN RATS. Celine Picard, Brigitte Ksas, Jean Fioramonti, Nina M. Griffiths, Ipsn, Fontenay, France; INRA, Toulouse, France. Background: Exposure to ionizing radiation often causes diarrhea, which has been attributed both to mucosal injury and alterations of intestinal motility. According to the release of 5-HT by irradiation and the role of 5-HT3 receptors in the control of intestinal motility and fluid movements, our aim was to determine whether a treatment with a 5-HT3 receptor antagonist attenuates the decrease of colonic motility and fluid absorption induced by irradiation in rats. Methods: Two groups of six male Wistar rats were chronically equipped with nichrome electrodes in the wall of the proximal colon for recording myoelectric activity. Colonic motility was recorded for 4 hours, 2 days before and on the 3rd and 7th days after abdominal 'Y irradiation (10 Gy; 6OCO). One group received saline and the other granisetron (0.3 mg/kg, s.c.) 2 days before, I hr, 1,3, and 7 days after irradiation. In addition following abdominal irradiation or sham-irradiation, fluid absorption was measured with an agarose gel cylinder inserted for 90 min in the lumen of the descending colon in anesthetized rats in controls (saline) and granisetron-treated animals (0.3 mg/kg, s.c.; I hr, day 1,3 and 7). Results: In absence of irradiation, the frequency of colonic long spike bursts (LSB), corresponding to individual contractions, was 9.6 ± 0.6 per 10 min, and net fluid absorption was 76.7 ± 7.0 ILl/cm2/h. These values were not significantly modified by granisetron. The frequency of LSB was reduced to 3.2 ± 0.3 and 4.4 ± 0.6 per 10 min on days 3 and 7 after irradiation, respectively. Similarly, fluid absorption was reduced to 7.7 ± 1.0 and 49.3 ± 6.3 ILl/cm2/h. Granisetron treatment significantly attenuated (p<0.05) the decrease of colonic motility and of fluid absorption, on the 3rd day after irradiation (6.3 ± 0.9 LSBI10 min and 11.8 ± 1.6 ILl/cm2/h) and restored values significantly not different from controls (p>0.05) on the T" day (8.8 ± 0.5 LSB/1O min and 60.1 ± 4.1 ILl/cm2/h) Conclusion: These results indicate that, in rats, a post-irradiation treatment with a 5-HT3 receptor antagonist reversed the alterations of colonic motility and fluid absorption on the 7th day after irradiation. Granisetron was kindly provided by Dr OJ Sanger, SmithKline Beecham.
Acupuncture is rapidly becoming popular for treatment of disorders which lack definitive therapy, including IBS , yet there are virtually no clinical trials which have examined its efficacy. This randomized double-blind study compared acupuncture (n=28; insertion of needles into skin with tape placed next to needles at 9 points for 20 minutes) to a validated placebo acupuncture technique (n=22;tapping a blunt needle on the skin and taping in place at the same points) in 50 patients with ROME positive IBS (80% female, age range 18-73 years). We proposed that a clinically relevant therapeutic benefit would be recognized only if there was a 40% overall improvement in response rate. Assuming a 50% placebo response, we determined (a=.05, (3=0.20) that 50 patients were required to detect a therapeutic benefit. Acupuncture was conducted twice weekly for four weeks by a Physiotherapist with Level I acupuncture accreditation. Patients were evaluated at baseline, 4 weeks, and 3 months. The two groups were well matched for age, symptom scores, Beck depression and State-Trait anxiety scores. The major outcome measure was individual patient-determined treatment success based on the achievement of individual patient expectations (percent improvement in symptoms) established prior to treatment (range 10-100%; no difference between groups). At completion of acupuncture therapy there was no significant difference in the patientdetermined treatment success rates between the acupuncture and placebo groups (57% vs 45%; respectively, p=0.57). The proportion of patients with increased Barostat rectal sensory thresholds was also not different (54% vs. 40%; respectively, p=0.39). Similarly, the proportion of the patients with increased thresholds was not different among those achieving patient-determined treatment success compared to those who did not. In contrast, McGill pain scores were markedly improved in both groups (acupuncture p
3169 PSYCHOLOGICAL THREAT PERCEPTION AND SYMPTOM SEVERITY IN PATIENTS WITH IRRITABLE BOWEL SYNDROME. Olafur S. Palsson, Marsha 1. Turner, David A. Johnson, Eastern Virginia Med Sch, Norfolk, VA. Irritable bowel syndrome (IBS) patients have been reported to score higher than control subjects on the psychological traits of neuroticism (Acta Psychiatr Scand, 1991;84:26-8, Gastroenterology 1990;98:1187-92, etc.) and social desirability (Int J Psychiatry Med, 1992;22:99-103). Both traits modulate cognitive processing of threatening or negative life experiences. This study expanded on the past work by examining whether IBS patients differ from healthy subjects on catastrophizing and absorption, two other personality traits which influence threat perception. The study also evaluated whether these traits influence self-report of IBS symptoms by the patients. Method: Subjects were 30 IBS patients (physician diagnosis plus Rome criteria; 21 females and 9 males; mean age = 36.5 years) and 30 age and gender matched healthy (no gastrointestinal disorders or significant gut symptoms) individuals. Subjects completed a 14-day bowel symptom log, the Eysenck Personality Inventory (EPI), the Tellegen Absorption Scale (TAS), the Catastrophizing subscale of the Dysfunctional Cognitions Inventory and the Marlowe-Crowne Social Desirability Scale (MCSDS). Results: IBS patients had higher scores on EPI Neuroticism (mean + standard deviation: 10.93 +/- 5.41 vs. 6.24 +/- 4.38; p<.OOI) and DCI Catastrophizing Scale (30.76+/-13.91 vs. 23.76 +/-6.64 ; p<.02), but no group differences were found in scores on the MCSDS (15.67 +/- 5.56 vs. 16.93 +/- 6.29; NS) or TAS (18.43 +/- 6.45 vs. 15.17 +/- 8.01 ; p=.09). Bowel movement frequency was positively correlated with neuroticism and catastrophizing scores (r = .44 and .42; p<.02), and neuroticism scores showed a negative relationship to stool consistency abnormality (r = -.37; p<.05). No significant correlations were observed between psychological variables and abdominal pain or abdominal distension. Discussion: The study replicated previous findings of higher neuroticism scores in IBS patients compared to healthy controls. Additionally, the patients had elevated catastrophizing scores, suggesting a tendency greater than in healthy individuals to predict the worst possible outcome in present and future life situations and to verbally and mentally amplify perceived threat. In contrast to previous report social desirability scores were not elevated. The influence of the four examined personality traits on bowel symptoms seems limited to neuroticism and catastrophizing promoting bowel movement frequency and neuroticism affecting stool consistency.
3171
ms.
AMITRIPTYLIN FOR THE TREATMENT OF Monique Riberdy-Poitras, Pierre Verrier, Victor Plourde, Michel Boivin, Pierre Poitras, Hosp Saint-Luc du CHUM, Montreal, PQ, Canada; CHUM St-Luc, Montreal, PQ, Canada. Low doses of amitriptylin (Ami) have been suggested for the management of functional bowel disorders such as irritable bowel syndrome (lliS). Our AIM was to verify the mode action of Ami in patients with lliS. METHODS: I) pts complaining of IBS identified by Rome criteria and with documented rectal hypersensitivity were included in this study; 2) 12 pts received Ami 10 mg hs for 2 weeks and then 25 mg hs for the following 4 weeks. 36 pts treated by a group psychotherapy (Psy) program could be used for comparison; 3) before and at the end of both treatments, the severity of the GI symptoms was assessed by a GI index and the pain threshold to rectal distensions was measured by a barostat programed for phasic ascending distensions. RESULTS: I) With Ami, GI index decreased from an initial value of 91.6 ± 5.6 to a score of 61.8 ± 9.1 at the end of treatment (p
AGAA617
3168
3170
A PLACEBO-CONTROLLED, DOUBLE-BLIND TRIAL OF ACUPUNCTURE IN THE TREATMENT OF IRRITABLE BOWEL SYNDROME( ras i Catherine Lowe, William T. Depew, Stephen 1. Vanner, Acad Univ, Kingston, ON, Canada.
ROLE OF 5-HT 3 RECEPTORS IN RADIATION-INDUCED ALTERATIONS OF COLONIC MOTILITY AND FLUID ABSORP· TION IN RATS. Celine Picard, Brigitte Ksas, Jean Fioramonti, Nina M. Griffiths, Ipsn, Fontenay, France; INRA, Toulouse, France. Background: Exposure to ionizing radiation often causes diarrhea, which has been attributed both to mucosal injury and alterations of intestinal motility. According to the release of 5-HT by irradiation and the role of 5-HT3 receptors in the control of intestinal motility and fluid movements, our aim was to determine whether a treatment with a 5-HT3 receptor antagonist attenuates the decrease of colonic motility and fluid absorption induced by irradiation in rats. Methods: Two groups of six male Wistar rats were chronically equipped with nichrome electrodes in the wall of the proximal colon for recording myoelectric activity. Colonic motility was recorded for 4 hours, 2 days before and on the 3rd and 7th days after abdominal 'Y irradiation (10 Gy; 6OCO). One group received saline and the other granisetron (0.3 mg/kg, s.c.) 2 days before, I hr, 1,3, and 7 days after irradiation. In addition following abdominal irradiation or sham-irradiation, fluid absorption was measured with an agarose gel cylinder inserted for 90 min in the lumen of the descending colon in anesthetized rats in controls (saline) and granisetron-treated animals (0.3 mg/kg, s.c.; I hr, day 1,3 and 7). Results: In absence of irradiation, the frequency of colonic long spike bursts (LSB), corresponding to individual contractions, was 9.6 ± 0.6 per 10 min, and net fluid absorption was 76.7 ± 7.0 ILl/cm2/h. These values were not significantly modified by granisetron. The frequency of LSB was reduced to 3.2 ± 0.3 and 4.4 ± 0.6 per 10 min on days 3 and 7 after irradiation, respectively. Similarly, fluid absorption was reduced to 7.7 ± 1.0 and 49.3 ± 6.3 ILl/cm2/h. Granisetron treatment significantly attenuated (p<0.05) the decrease of colonic motility and of fluid absorption, on the 3rd day after irradiation (6.3 ± 0.9 LSBI10 min and 11.8 ± 1.6 ILl/cm2/h) and restored values significantly not different from controls (p>0.05) on the T" day (8.8 ± 0.5 LSB/1O min and 60.1 ± 4.1 ILl/cm2/h) Conclusion: These results indicate that, in rats, a post-irradiation treatment with a 5-HT3 receptor antagonist reversed the alterations of colonic motility and fluid absorption on the 7th day after irradiation. Granisetron was kindly provided by Dr OJ Sanger, SmithKline Beecham.
Acupuncture is rapidly becoming popular for treatment of disorders which lack definitive therapy, including IBS , yet there are virtually no clinical trials which have examined its efficacy. This randomized double-blind study compared acupuncture (n=28; insertion of needles into skin with tape placed next to needles at 9 points for 20 minutes) to a validated placebo acupuncture technique (n=22;tapping a blunt needle on the skin and taping in place at the same points) in 50 patients with ROME positive IBS (80% female, age range 18-73 years). We proposed that a clinically relevant therapeutic benefit would be recognized only if there was a 40% overall improvement in response rate. Assuming a 50% placebo response, we determined (a=.05, (3=0.20) that 50 patients were required to detect a therapeutic benefit. Acupuncture was conducted twice weekly for four weeks by a Physiotherapist with Level I acupuncture accreditation. Patients were evaluated at baseline, 4 weeks, and 3 months. The two groups were well matched for age, symptom scores, Beck depression and State-Trait anxiety scores. The major outcome measure was individual patient-determined treatment success based on the achievement of individual patient expectations (percent improvement in symptoms) established prior to treatment (range 10-100%; no difference between groups). At completion of acupuncture therapy there was no significant difference in the patientdetermined treatment success rates between the acupuncture and placebo groups (57% vs 45%; respectively, p=0.57). The proportion of patients with increased Barostat rectal sensory thresholds was also not different (54% vs. 40%; respectively, p=0.39). Similarly, the proportion of the patients with increased thresholds was not different among those achieving patient-determined treatment success compared to those who did not. In contrast, McGill pain scores were markedly improved in both groups (acupuncture p
3169 PSYCHOLOGICAL THREAT PERCEPTION AND SYMPTOM SEVERITY IN PATIENTS WITH IRRITABLE BOWEL SYNDROME. Olafur S. Palsson, Marsha 1. Turner, David A. Johnson, Eastern Virginia Med Sch, Norfolk, VA. Irritable bowel syndrome (IBS) patients have been reported to score higher than control subjects on the psychological traits of neuroticism (Acta Psychiatr Scand, 1991;84:26-8, Gastroenterology 1990;98:1187-92, etc.) and social desirability (Int J Psychiatry Med, 1992;22:99-103). Both traits modulate cognitive processing of threatening or negative life experiences. This study expanded on the past work by examining whether IBS patients differ from healthy subjects on catastrophizing and absorption, two other personality traits which influence threat perception. The study also evaluated whether these traits influence self-report of IBS symptoms by the patients. Method: Subjects were 30 IBS patients (physician diagnosis plus Rome criteria; 21 females and 9 males; mean age = 36.5 years) and 30 age and gender matched healthy (no gastrointestinal disorders or significant gut symptoms) individuals. Subjects completed a 14-day bowel symptom log, the Eysenck Personality Inventory (EPI), the Tellegen Absorption Scale (TAS), the Catastrophizing subscale of the Dysfunctional Cognitions Inventory and the Marlowe-Crowne Social Desirability Scale (MCSDS). Results: IBS patients had higher scores on EPI Neuroticism (mean + standard deviation: 10.93 +/- 5.41 vs. 6.24 +/- 4.38; p<.OOI) and DCI Catastrophizing Scale (30.76+/-13.91 vs. 23.76 +/-6.64 ; p<.02), but no group differences were found in scores on the MCSDS (15.67 +/- 5.56 vs. 16.93 +/- 6.29; NS) or TAS (18.43 +/- 6.45 vs. 15.17 +/- 8.01 ; p=.09). Bowel movement frequency was positively correlated with neuroticism and catastrophizing scores (r = .44 and .42; p<.02), and neuroticism scores showed a negative relationship to stool consistency abnormality (r = -.37; p<.05). No significant correlations were observed between psychological variables and abdominal pain or abdominal distension. Discussion: The study replicated previous findings of higher neuroticism scores in IBS patients compared to healthy controls. Additionally, the patients had elevated catastrophizing scores, suggesting a tendency greater than in healthy individuals to predict the worst possible outcome in present and future life situations and to verbally and mentally amplify perceived threat. In contrast to previous report social desirability scores were not elevated. The influence of the four examined personality traits on bowel symptoms seems limited to neuroticism and catastrophizing promoting bowel movement frequency and neuroticism affecting stool consistency.
3171
ms.
AMITRIPTYLIN FOR THE TREATMENT OF Monique Riberdy-Poitras, Pierre Verrier, Victor Plourde, Michel Boivin, Pierre Poitras, Hosp Saint-Luc du CHUM, Montreal, PQ, Canada; CHUM St-Luc, Montreal, PQ, Canada. Low doses of amitriptylin (Ami) have been suggested for the management of functional bowel disorders such as irritable bowel syndrome (lliS). Our AIM was to verify the mode action of Ami in patients with lliS. METHODS: I) pts complaining of IBS identified by Rome criteria and with documented rectal hypersensitivity were included in this study; 2) 12 pts received Ami 10 mg hs for 2 weeks and then 25 mg hs for the following 4 weeks. 36 pts treated by a group psychotherapy (Psy) program could be used for comparison; 3) before and at the end of both treatments, the severity of the GI symptoms was assessed by a GI index and the pain threshold to rectal distensions was measured by a barostat programed for phasic ascending distensions. RESULTS: I) With Ami, GI index decreased from an initial value of 91.6 ± 5.6 to a score of 61.8 ± 9.1 at the end of treatment (p