Table 1.
Drug effects on visceral sensitivity in IBS
| Drug | Dose | IBS study subjects | Study design | Barostat methodology | Effect on sensitivity in IBS | Effect on motor function |
Effect on IBS symptoms |
Conclusions from phase II and III trials |
|---|---|---|---|---|---|---|---|---|
| Opiates | ||||||||
| Fentanyl40 | Two doses (HD and LD), bolus + infusion | 10 IBS (6 F) | DB, PC, crossover | Phasic pressure | HD and LD: ↑ DiscTh, ↑ SensTh HD: ↑ PainTh | None | NR* | NR |
| Fedotozine—κ agonist48 | 100 mg single dose | 14 IBS (8 F) | PC, crossover | Phasic pressure | ↑ PainTh, ↑ SensTh | None | NR | Small but significant change in pain in small trial49 |
| Asimodoline—κ agonist50 | 0.5 mg single dose | 20 IBS (20 F), all hypersensitive | DB, PC, crossover | Phasic pressure | No change in PainTh, ↓ sensory ratings | None | NR | NR |
| 5-HT | ||||||||
| Alosetron51 | Either 0.25 mg bd or 4 mg bd × 7 days | 22 IBS (9 F) | PC, parallel group study | Phasic pressure | No effect on PainTh (pressure) | ↑ compliance | Effective for global symptom relief52 | |
| Alosetron53 | Either 1 mg alosetron or 4 mg alosetron bd × 4 weeks | 25 IBS (19 F) | PC, parallel group study | Phasic pressure | ? | ↑ rectal compliance | ||
| Ondansetron54 | One dose at 0.15 mg/kg | 12 IBS (6 F) | DB, PC, parallel group study | Phasic pressure | No effect on sensitivity | ↑ rectal compliance | NA | No effect in pilot study55 |
| Ondansetron56 | 16 mg, 3 times/day | 6 IBS | PC, crossover | ? | ↑ SensTh | None | Decreased number of episodes of abdominal pain | |
| Ondansetron57 | Single dose of 0.15 mg/kg | 5 IBS (3 F) | PC, parallel group study? | Phasic pressure | No change in sensitivity | None | NR | |
| Granisetron58 | Either 40 μg/kg or 160 μg/kg | 12 IBS (8 F) | DP, PC, crossover | Phasic pressure or volume?? | ↑ DisTh, ↑ UrgeTh | None | Participants noted constipation | NR |
| Tegaserod63 | 6 mg bid | 49 IBS (49 F) | DB, PC, parallel group study | Phasic sigmoid pressure | No effect | ↑ sigmoid accomodation | No symptom change | Effective for global symptoms and constipation59 |
| Talnetant60 | 25 and 100 mg | 102 healthy controls (60 F) | DB, PC, parallel group study | Phasic rectal pressure | No effect | No effect | NA | Not different from placebo61 |
| Antidepressant | ||||||||
| Amitriptyline62 | 10 mg/day × 2 weeks and then 25 mg h for the following 4 weeks | 12 IBS (7 F) | Parallel group study? | Phasic pressure | ↑ PainTh | None | Symptom reduction | Some effectiveness in meta-analysis and in high quality clinical trial63,64 |
| Fluoxetine65 | 20 mg × 6 weeks | 40 IBS | DB, PC, parallel group study | Phasic pressure and volume ramp | No change in sensitivity. ↓ abdominal pain in hypersensitivity patients | none | Reduced the number of patients reporting significant abdominal pain | May be effective. Positive effect on pain in small trial65 |
| Other CNS | ||||||||
| Gabapentin66 | 600 mg/day × 5 days | 43 IBS-D (no sex data) | DB, PC, parallel group study | Phasic pressure | ↑ PainTh, DiscTh | ↑ compliance | NR | NR |
| Octreotide67 | 1.25 μg/kg (sc) | 10 IBS | DB, PC, crossover | Phasic pressure | ↑ PainTh, DiscTh | None | NR | Preliminary evidence suggests some effectiveness on IBS symptoms68 |
| Octreotide69 | 100 μg (sc) | 8 IBS-D | DB, PC, crossover | Ramp volume | ↑ tolerance | ↑ compliance | NR | |
| Octreotide70 | 7 IBS (4 F), 9 IBS (9 F) | DB, PC, crossover (2 studies) | Phasic pressure alone and after sigmoid stimulation | ↑ DiscTh, ↓ sensitisation from sigmoid stimulation | None | NR | ||
bd, twice a day; CNS, central nervous system; DB, double-blind; DiscTh, discomfort threshold; F, female; HD, high dose; 5-HT, 5-hydroxytryptamine; IBS, irritable bowel syndrome; IBS-D, diarrhoea-predominant irritable bowel syndrome; LD, low dose; NA, not applicable; NR, not reported; PainTh, pain threshold; PC, placebo-controlled; SensTh, sensory threshold; sc, subcutaneous; UrgeTh, urgency threshold.