A systematic review with meta-analysis «Ford AC, Lacy BE, Harris LA, et al. Effect of Anti...»1 compared antidepressants with placebo and found a favorable effect on general symptoms of IBS with tricyclic and SSRI antidepressants and specifically on abdominal pain with tricyclic antidepressants. Antidepressants increased the total adverse events (RR 1.56, 95% CI 1.23–1.98). Drowsiness and dry mouth were the most common adverse effects. The study did not report estimates for specific adverse events.
The largest RCT to this day including 463 patients compared low dose tricyclic antidepressants with placebo and found effect on general symptoms and abdominal pain. At 6 months follow up, Intervention group had a mean of −27,0 points (−46,9 to −7,1) less symptoms (IBS-SSS) compared to control (about 14% less than control group).
| Reference | Study type | Population | Intervention and comparison | Outcomes | Risk of bias |
|---|---|---|---|---|---|
| RCT=randomized controlled trial; SR=systematic review; MA=meta-analysis; SGA= Subjective global assessment | |||||
| «Ford AC, Lacy BE, Harris LA, et al. Effect of Anti...»1 | SR/MA | Patients 16 years or older, with a diagnosis of IBS based on clinician's opinion or specific diagnostic criteria. Minimum duration of therapy and follow-up ≥ 7 days | Antidepressant or placebo | Effect assessed based on global IBS symptoms or abdominal pain (proportion of patients without improvement) | High |
| «Ford AC, Wright-Hughes A, Alderson SL, et al. Amit...»2 | RCT | 18 years or older, with a primary care diagnosis of IBS having tried first-line treatments |
Titrated low-dose oral amitriptyline or placebo for 6 months |
Primary (1): IBS symptoms, measured by the IBS-SSS at 6 months Secondary (2): relief of IBS symptoms (SGA) at 6 months |
High |
| Reference | Comments |
|---|---|
| «Ford AC, Lacy BE, Harris LA, et al. Effect of Anti...»1 | Dropout rates varied between 0-48%. Most trials had insufficient reporting of allocation concealment. |
| «Ford AC, Wright-Hughes A, Alderson SL, et al. Amit...»2 | 25% drop out rate. Inclusion criteria: First line treatments including dietary changes and lifestyle advice, soluble fibre, antispasmodics, laxatives, or antidiarrhoeals, without success, had active symptoms, scoring ≥ on the IBS-SSS, normal haemoglobin, white cell and platelet count, and C-reactive protein within 6 months; negative anti-tissue transglutaminase antibodies; no evidence of suicidal ideation Main exclusion criteria: meeting fast-track referral criteria for other bowel diseases, pregnancy, breastfeeding; current use of, or allergy or contraindications to, a tricyclic antidepressant |
Results
| Reference | Number of studies and number of patients (I/C) | Follow-up time | Absolute number of events (%) I | Absolute number of events (%) C | Relative effect (95% CI) | |
|---|---|---|---|---|---|---|
| Level of evidence: moderate The quality of evidence is downgraded due to study limitations I=intervention; C=comparison; CI=confidence interval |
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| «Ford AC, Lacy BE, Harris LA, et al. Effect of Anti...»1 | 18 RCT with 1127 patients (I 612, C 515) | 1-3 months | 266 | 345 | RR 0.66 (0.57-0.76) | |
| Reference | Number of studies and number of patients (I/C) | Follow-up time | Absolute number of events (%) I | Absolute number of events (%) C | Relative effect (95% CI) | |
|---|---|---|---|---|---|---|
| Level of evidence: moderate The quality of evidence is downgraded due to study limitations I=intervention; C=comparison; CI=confidence interval |
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| «Ford AC, Lacy BE, Harris LA, et al. Effect of Anti...»1 | 12 RCTs; 787 patients (I 436, C 351) | 1-3 months | 186 | 224 | 0.65 (0.55-0.77) | |
| Reference | Number of studies and number of patients (I/C) | Follow-up time | Absolute number of events (%) I | Absolute number of events (%) C | Relative effect (95% CI) | |
|---|---|---|---|---|---|---|
| Level of evidence: moderate The quality of evidence is downgraded due to study limitations I=intervention; C=comparison; CI=confidence interval |
||||||
| «Ford AC, Lacy BE, Harris LA, et al. Effect of Anti...»1 | 7 RCTs; 357 patients (I 176, C 180) | 1-3 months | 80 | 121 | RR 0.68 (0.51–0.91) | |
| Reference | Number of studies and number of patients (I/C) | Follow-up time | Absolute number of events (%) I | Absolute number of events (%) C | Relative effect (95% CI) | |
|---|---|---|---|---|---|---|
| Level of evidence: moderate The quality of evidence is downgraded due to study limitations I=intervention; C=comparison; CI=confidence interval |
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| «Ford AC, Lacy BE, Harris LA, et al. Effect of Anti...»1 | 7 RCTs; 351 patients (I 182, C 169) | 1.5-3 months | 87 | 123 | RR 0.62 (0.43-0.88) | |
| Reference | Number of studies and number of patients (I/C) | Follow-up time | Absolute change in outcome I | Absolute change in outcome measure (points in IBS-SSS) C | Relative effect (95% CI) | |
|---|---|---|---|---|---|---|
| Level of evidence: low The quality of evidence is downgraded due to study limitations and imprecision. I=intervention; C=comparison; CI=confidence interval |
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| «Ford AC, Wright-Hughes A, Alderson SL, et al. Amit...»2 | 232/231 | 6 m | -99.2 | -68.9 | -27.0 (-46.9 to -7.1) | |