Intervenciones farmacológicas para el dolor abdominal recurrente en niños
References
References to studies included in this review
References to studies excluded from this review
Additional references
References to other published versions of this review
Characteristics of studies
Characteristics of included studies [ordered by study ID]
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| Methods | Design: 3‐arm randomised placebo‐controlled trial Duration: 4 weeks | |
| Participants | Country: Iran Setting: paediatric gastroenterology outpatient clinic Sample size: 120 children (40 synbiotic, 40 peppermint oil, 40 control) Gender: peppermint oil group: 15 girls and 19 boys; control group: 17 girls and 8 boys Mean age (SD): 7.06 (+/‐2.38) years peppermint oil group; 7.42(+/‐2.49) years control group Dropouts/withdrawals: 32 withdrawals, number analysed = 88 Diagnosis: functional gastrointestinal disorders using Rome III (Rasquin 2006) | |
| Interventions | Intervention: Colpermin (peppermint oil 187 mg capsule), 1 capsule if < 45 kg and 2 capsules if > 45 kg), 3 x day, 30 minutes before each meal Control: folic acid tablet (1 mg), 1 tablet, once daily, 30 minutes before breakfast or lunch 3rd arm: synbiotic Lactol tablet (containing a probiotic and fructo‐oligosaccharide) (see dietary review Newlove‐Delgado in press for this comparison) | |
| Outcomes |
| |
| Notes | Study dates: September 2012 to August 2014 Funding: not stated Conflicts of interest: not reported | |
| Risk of bias | ||
| Bias | Authors' judgement | Support for judgement |
| Random sequence generation (selection bias) | Unclear risk | The authors state that participants were randomised in blocks, but give no details of the method of random sequence generation. |
| Allocation concealment (selection bias) | Unclear risk | The authors do not acknowledge this concept in the paper. In personal correspondence, the authors reported that it was not important (Asgarshirazi 2016 [pers comm]). Therefore, on balance, we judged this to be at unclear of risk of bias. |
| Blinding of participants and personnel (performance bias) | Unclear risk | The study authors do not specifically state that participants were blinded, although they do say that the nurse that carried out the questionnaire was blinded. |
| Blinding of outcome assessment (detection bias) | Unclear risk | As above, note also that the placebo regimen of folic acid tablets was once daily and the intervention regimen of peppermint oil capsules was 3 times daily. These different preparations and timings could have introduced bias, as the outcome was self reported and therefore influenced by the participants experience. |
| Incomplete outcome data (attrition bias) | High risk | 32 participants were excluded or withdrawn after randomisation. Attrition differed between the groups, 15% of the intervention group and 38% of the placebo group. |
| Selective reporting (reporting bias) | Low risk | All outcomes in the methods appear to be reported. |
| Other bias | High risk | No power calculation. The intervention and placebo groups differed at baseline: duration of pain in the intervention group was 67.05 mean minutes/day (SD +/‐ 36.97) and the placebo group was 53.4 mean minutes/day (SD +/‐ 16.81). |
| Methods | Design: double‐blinded, placebo‐controlled, randomised trial Duration: 13 weeks | |
| Participants | Country: USA Setting: private paediatric gastroenterology outpatient clinic Sample size: 33 children (intervention 16, control 16) Gender: 9 boys, 24 girls Mean age: intervention 15.3 years; control 14.2 years. Overall range 12 to 18 years Dropouts/withdrawals: 0 Diagnosis: meet the Rome II criteria for IBS (Rasquin‐Weber 1999) | |
| Interventions | Intervention: 7‐week course of oral amitriptyline (10 mg if 30 to 50 kg, 20 mg if 50 to 80 kg, 30 mg if > 80 kg), taken at night Control: placebo | |
| Outcomes |
Timing of outcome assessment: measured at 6, 10, and 13 weeks | |
| Notes | Study dates: 2002 to 2005 Funding: James and Diane Brooks Medical Research Foundation and AstraZeneca Conflicts of interest: not mentioned | |
| Risk of bias | ||
| Bias | Authors' judgement | Support for judgement |
| Random sequence generation (selection bias) | Unclear risk | The authors state that participants were randomised, but give no details of the method of randomisation. |
| Allocation concealment (selection bias) | High risk | The authors do not mention this concept in the paper. |
| Blinding of participants and personnel (performance bias) | Unclear risk | This is mentioned in the title but no details are provided. |
| Blinding of outcome assessment (detection bias) | Unclear risk | The outcome measurement is self assessed, therefore if the participant is blinded so too is the outcome assessment. No details of the blinding are provided. |
| Incomplete outcome data (attrition bias) | Low risk | The authors state that no participants dropped out after starting treatment. |
| Selective reporting (reporting bias) | High risk | The authors state in their methods that improvement in overall quality of life score is the primary outcome but provide no details of a threshold regarded as improvement. At baseline, the quality of life score for the intervention group was 14% lower than that of the placebo group, 109.4 and 127.5 respectively. In the analysis, at 10 and 13 weeks' follow‐up, the quality of life score was 128.0 and 126.2 respectively for the intervention group and 129.4 and 129.8 respectively for the placebo group. The authors conclude that the number of participants with a greater than 15% improvement is significantly higher in the intervention group; this could be wholly explained by the difference at baseline. This may also be a post‐hoc analysis, as the authors do not mention this in the methods. The authors also selected some symptoms from the functional abdominal pain score and reported these as improved, e.g. periumbilical and right lower quadrant pain, but abdominal pain in other areas showed no improvement with the intervention. |
| Other bias | High risk | There is no power calculation. Baseline data of the participants are not provided. Compliance with the intervention is mentioned. There is no raw data to verify the statistics quoted. We wrote to the authors to request these data but received no response. The validity of the outcome assessment tool or clinical relevance of the reported outcomes are not mentioned. For example, is a 15% improvement in the quality of life scale at 13 weeks, but not at 10 weeks, clinically important? The number of participants is small and the follow‐up is short. |
| Methods | Design: double‐blinded, placebo‐controlled, randomised trial Duration: 2 weeks | |
| Participants | Country: USA Setting: paediatric gastroenterology clinic at a children's hospital and an outreach clinic Sample size: 75 children (intervention 49, control 26) Gender: intervention 15 boys, 34 girls; control 6 boys, 20 girls Mean age: intervention 12.5 years (SD 3.01); control 13.16 years (SD 2.97) Dropouts/withdrawals: 5: intervention 3, control 2 Diagnosis: Rome II criteria for IBS, functional dyspepsia, functional abdominal pain, or abdominal migraine (Rasquin‐Weber 1999) | |
| Interventions | Intervention: 550 mg rifaximin 3 times daily for 10 days Control: placebo | |
| Outcomes |
Timing of outcome assessment: 2 weeks | |
| Notes | 10 symptoms = bloating, excess gas, incomplete evacuation, abdominal pain, diarrhoea, constipation, urgency, passage of mucus, straining, faecal soiling Study dates: 2010 Funding: the study was funded by Salix Pharmaceuticals, Saban Research Institute, and Children's Hospital of Los Angeles Conflicts of interest: none reported | |
| Risk of bias | ||
| Bias | Authors' judgement | Support for judgement |
| Random sequence generation (selection bias) | Unclear risk | The authors state that participants were randomised, but provide no details of the method of randomisation. |
| Allocation concealment (selection bias) | Low risk | The authors state that randomisation was performed by personnel not associated with the study and that the study personnel were blinded. This implies allocation concealment. |
| Blinding of participants and personnel (performance bias) | Low risk | The authors state that the participants and personnel were blinded and that a matching placebo was used. |
| Blinding of outcome assessment (detection bias) | Low risk | The outcomes were measured by self report in a questionnaire and the participants were blinded. |
| Incomplete outcome data (attrition bias) | Low risk | The authors state that outcome assessment is missing for 5 participants, 3 from the intervention group and 2 from the placebo group. This is a low number of loss to follow‐up and within what would be expected for any study. There was no differential loss to follow‐up between the groups. |
| Selective reporting (reporting bias) | Unclear risk | The authors do not present the raw data, i.e. from the 10‐point visual analogue scale of GI symptoms or the overall improvement score. They provide only a statement that none of the differences were significant. We wrote to the authors to provide the raw data to verify this but received no response. We are therefore unable to comment on the completeness of the outcome data or the degree of selective reporting. |
| Other bias | High risk | The power calculation is not based on a primary outcome but a laboratory test ‐ the detection of small intestinal bacteria overgrowth ‐ and is therefore not valid. The outcome is measured by self report for 10 symptoms, but the validity of this method is not mentioned. The number of participants is small and the follow‐up is short. |
| Methods | Design: double‐blinded, placebo‐controlled, randomised trial Duration: 3 weeks | |
| Participants | Country: Switzerland Setting: patients referred to the Department of Paediatric Gastroenterology and Nutrition at the University Children's Hospital, Zurich Sample size: 37 children (intervention 20, control 17) Gender: intervention 9 boys, 11 girls; control 7 boys, 10 girls Mean age: intervention 10.6 years (SD not reported; range not reported); control 11.4 years (SD not reported; range not reported) Dropouts/withdrawals: 3, not known from which group Diagnosis: Apley's criteria for RAP (Apley 1958) | |
| Interventions | Intervention: 6 mg/kg/day trimethoprim and 30 mg/kg/day sulfamethoxazole in 2 divided doses for 7 days Control: placebo twice daily for 7 days | |
| Outcomes |
Timing of outcome assessment: 2 weeks | |
| Notes | Study dates: 2004 to 2008 Funding: not stated in the paper Conflicts of interest: none reported | |
| Risk of bias | ||
| Bias | Authors' judgement | Support for judgement |
| Random sequence generation (selection bias) | Unclear risk | The authors state that participants were randomised, but provide no details of the method of randomisation. |
| Allocation concealment (selection bias) | Unclear risk | The authors state that randomisation occurred after obtaining written, informed consent, but no additional information is provided. It is therefore unclear if there was allocation concealment. |
| Blinding of participants and personnel (performance bias) | Low risk | The authors state that the intervention was blinded and a placebo was used. |
| Blinding of outcome assessment (detection bias) | Low risk | Outcome was self reported and the participants were blinded. |
| Incomplete outcome data (attrition bias) | Low risk | The authors state that 3 participants withdrew from the study after inclusion, but this is unlikely to have significantly altered the results. |
| Selective reporting (reporting bias) | Low risk | The primary outcome, Pain Index, was reported for all participants. |
| Other bias | Unclear risk | The power calculation is inadequate for this outcome measurement, as it is based on the breath test findings and not the primary outcome. The baseline data were presented and showed no imbalances. The number of participants is small and the follow‐up is short. The funding is not stated. The authors report no conflicts of interest. |
| Methods | Design: randomised controlled trial comparing trimebutine with usual care Duration: 3 weeks | |
| Participants | Country: Turkey Setting: patients attending the general paediatric clinic at the Istanbul University Hospital, Department of Paediatric Gastroenterology Sample size: 78 children (intervention 39, control 39) Gender: 31 boys, 47 girls. Distribution between groups not given. Mean age: 9.79 years (SD 3.45). Distribution between groups not given. Dropouts/withdrawals: 0 Diagnosis: IBS according to the Rome III criteria (Rasquin 2006) | |
| Interventions | Intervention: 3 mg/kg/day trimebutine maleate, in 3 divided doses for 3 weeks Control: usual care | |
| Outcomes |
Timing of outcome assessment: 3 weeks | |
| Notes | Study dates: 2007 to 2008 Funding: none Conflicts of interest: none reported | |
| Risk of bias | ||
| Bias | Authors' judgement | Support for judgement |
| Random sequence generation (selection bias) | Unclear risk | The authors state that participants were randomised, but give no details of the method of randomisation. |
| Allocation concealment (selection bias) | High risk | This concept is not mentioned in the paper. |
| Blinding of participants and personnel (performance bias) | High risk | The participants and study personnel could not have been blinded as there was no placebo for the control group, who received standard care instead. |
| Blinding of outcome assessment (detection bias) | High risk | The parents were asked to report the outcome, and they would have known whether the child was taking trimebutine or not. |
| Incomplete outcome data (attrition bias) | Unclear risk | The authors do not mention this; the raw data is not reported, only the percentage of children who improved. We therefore cannot be sure about the loss to follow‐up or how the missing data were handled. |
| Selective reporting (reporting bias) | Low risk | The authors state that parental assessment of pain relief was their only outcome. |
| Other bias | High risk | No power calculation was performed and no baseline data are given. Compliance with the intervention is not mentioned. The outcome measurement is not validated. The number of participants is small and the follow‐up is short. We wrote to the authors to request details regarding the above issues, but received no response. |
| Methods | Design: randomised, placebo‐controlled trial Duration: insufficient detail. The intervention was given for 8 weeks but when the outcomes were measured is not stated. | |
| Participants | Country: Sri Lanka Setting: outpatient clinic of the university paediatric unit Sample size: 100 children Gender: no details about the children at recruitment. In the 89 children that completed the study, 33/47 in the intervention group were girls, and 22/42 in the placebo group were girls. Mean age: no details. The authors state that the study was designed to recruit children aged 5 to 12 years. Dropouts/withdrawals: 11 Diagnosis: abdominal pain‐predominant functional gastrointestinal diseases fulfilling Rome III criteria (Rasquin 2006) | |
| Interventions | Intervention: domperidone 10 mg, 3 times per day, before meals for 8 weeks Control: placebo | |
| Outcomes | Primary outcomes:
Secondary outcomes were significant improvement in:
Timing of outcome assessment: no details | |
| Notes | Study dates: no details Funding: no details Conflicts of interest: no details This study is published as a conference abstract. We wrote to the authors and received no further information (Martin 2016a [pers comm]; Martin 2016d [pers comm]). | |
| Risk of bias | ||
| Bias | Authors' judgement | Support for judgement |
| Random sequence generation (selection bias) | Low risk | The authors state that computer‐generated random numbers were used. |
| Allocation concealment (selection bias) | Unclear risk | The authors do not mention this. |
| Blinding of participants and personnel (performance bias) | Low risk | The authors state that participants were blinded. |
| Blinding of outcome assessment (detection bias) | Low risk | The authors state that participants and investigators who assessed outcome measures were blinded. |
| Incomplete outcome data (attrition bias) | Unclear risk | There is insufficient detail in the published information to assess this. |
| Selective reporting (reporting bias) | Low risk | All stated outcomes appear to be reported, although with very limited data. |
| Other bias | Unclear risk | There is insufficient detail in the published information to assess this. |
| Methods | Design: randomised controlled trial comparing tegaserod plus laxative with laxative alone Duration: 4 weeks | |
| Participants | Country: USA Setting: medical centre in North America (no further detail given by authors) Sample size: 48 children (intervention 21, control 27) Gender: intervention 8 boys, 13 girls; control 11 boys, 16 girls Mean age: intervention 15.1 years (SD not reported); control 15.37 years (SD not reported) Dropouts/withdrawals: 0 Diagnosis: constipation‐predominant IBS according to Rome II criteria (Rasquin‐Weber 1999) | |
| Interventions | Intervention: 6 mg tegaserod once daily, oral, on an empty stomach Control: usual care | |
| Outcomes |
Timing of outcome assessment: 4 weeks | |
| Notes | Study dates: 2006 Funding: authors state no external financial support was received Conflicts of interest: none reported | |
| Risk of bias | ||
| Bias | Authors' judgement | Support for judgement |
| Random sequence generation (selection bias) | Low risk | Authors state that they used a simple random numbers table to allocate the treatment groups. |
| Allocation concealment (selection bias) | Unclear risk | This concept is not mentioned in the paper. |
| Blinding of participants and personnel (performance bias) | High risk | The control group was not given a placebo, therefore if informed consent was obtained before inclusion, participants would have been aware of the implications of their group allocation. The authors state in the discussion that the participants were unaware of the different groups. This is concerning. We asked the authors about this but have not received a reply. |
| Blinding of outcome assessment (detection bias) | High risk | Self reported outcome and therefore not blinded, as explained in performance bias section, see above |
| Incomplete outcome data (attrition bias) | Low risk | There appears to be no loss to follow‐up. |
| Selective reporting (reporting bias) | Unclear risk | The authors report all the outcomes they stated in the methods, but it is unclear from the methods if the definition of a good pain reduction was a prespecified outcome; it may be post‐hoc analysis. |
| Other bias | Unclear risk | The 2 groups are similar at baseline. A power calculation is performed. The eligibility criteria are stated. It is unclear if the pain‐rating tool is validated as the authors state "standard pain rating scale" but give no further details. |
| Methods | Design: double‐blinded, placebo‐controlled, randomised trial Duration: 2 weeks | |
| Participants | Country: USA Setting: 3 specialist paediatric gastroenterology departments Sample size: 42 children (intervention 21, control 21) Gender: 17 boys, 25 girls. Distribution between groups not given. Mean age: 12 years (range 8 to 17 years). Distribution between groups not given. Dropouts/withdrawals: 8 (4 from intervention, 4 from control) Diagnosis: RAP, defined by Apley (Apley 1958) | |
| Interventions | Intervention: peppermint oil capsule taken 3 times daily Control: placebo (arachis oil) capsule | |
| Outcomes |
Timing of outcome assessment: 2 weeks | |
| Notes | Study dates: 1999 Funding: Tillotts Pharma AG Switzerland Conflicts of interest: none declared | |
| Risk of bias | ||
| Bias | Authors' judgement | Support for judgement |
| Random sequence generation (selection bias) | Unclear risk | The authors state this was a randomised controlled trial, but give no details of method of randomisation. |
| Allocation concealment (selection bias) | Unclear risk | The authors did not mention this concept. |
| Blinding of participants and personnel (performance bias) | Unclear risk | The authors state that the trial was double‐blinded and describe that the same company produced identical intervention and placebo tablets. However, it is unclear who, if any, of the study personnel were blinded. |
| Blinding of outcome assessment (detection bias) | Unclear risk | There is insufficient information in the paper to judge this because the outcome was based on clinician judgement, parent report, and child report, and the blinding of all these outcome assessors was not explained. |
| Incomplete outcome data (attrition bias) | Low risk | The authors state that 8 participants withdrew from the study. Reasons for withdrawal (4 from each group) are clearly stated in the paper and appear not to be related to treatment effects (2 because of long travel distances to the clinic; 2 because they were prescribed antibiotics for other reasons; 4 because they were unable to swallow pills). |
| Selective reporting (reporting bias) | High risk | The authors do not report all 5 outcomes mentioned in the methods section. |
| Other bias | Unclear risk | There was no power calculation. The eligibility criteria were clearly stated. The authors state that the groups were similar at baseline, but the details are not reported. Compliance with the intervention is unclear. The follow‐up is short. |
| Methods | Design: double‐blinded, placebo‐controlled, randomised trial Duration: 4 weeks | |
| Participants | Country: India Setting: tertiary paediatric gastroenterology clinic Sample size: 132 children (intervention 66, control 66) Gender: intervention group: 33 boys, 33 girls; control group: 39 boys, 27 girls Mean age: intervention group: 7.1 (+/‐ 2.1); control group: 7.4 (+/‐ 2.6) Dropouts/withdrawals: 8 (4 from intervention, 4 from control) Diagnosis: RAP, defined by Apley (Apley 1958) | |
| Interventions | Intervention: drotaverine 20 mg (10 mL) liquid 3 x daily for children 4 to 6 years, 40 mg tablet 3 x daily for children > 6 years Control: placebo Both groups could have extra doses if pain was experienced. | |
| Outcomes |
Timing of outcome assessment: 4 weeks | |
| Notes | Study dates: September 2012 to September 2013 Funding: Walter Bushnell Pvt. Ltd. The company supplied a grant and medication for the study. They had no role in trial design, data collection, or manuscript preparation. Conflicts of interest: none declared | |
| Risk of bias | ||
| Bias | Authors' judgement | Support for judgement |
| Random sequence generation (selection bias) | Low risk | Authors state that they used computer‐generated block randomisation with variable block sizes. Stratified for age (4 to 6 and > 6 years). |
| Allocation concealment (selection bias) | Low risk | Clearly explained by authors |
| Blinding of participants and personnel (performance bias) | Low risk | Clearly explained by authors |
| Blinding of outcome assessment (detection bias) | Low risk | The outcomes were self and parental reported, therefore participant blinding meant the outcome assessment was also blinded. |
| Incomplete outcome data (attrition bias) | Low risk | Low loss to follow‐up: 6 from placebo group and 2 from intervention group |
| Selective reporting (reporting bias) | High risk | The outcomes explained in the methods were not all reported, e.g. results for pain severity are not given. In addition, the outcome 'number of school days missed in 4 weeks' reported in the results was not mentioned in the methods. |
| Other bias | High risk | We were concerned that the method of giving further drug doses if pain is reported could alter the trial outcome reporting, as if the drug works the child may ask for it more frequently. Therefore, administration of the intervention and outcome assessment are not independent. |
| Methods | Design: double‐blinded, placebo‐controlled, randomised trial of mebeverine versus placebo Duration: 12 weeks | |
| Participants | Country: Iran Setting: paediatric gastroenterology outpatient clinic Sample size: 115 children (intervention 59, control 56) Gender: 39 boys, 48 girls (children who completed follow‐up) Mean age: 8.5 years (SD 2.1 years) for all children who completed follow‐up. Distribution between treatment groups not given. Dropouts/withdrawals: intervention 19, control 17 Diagnosis: functional abdominal pain, defined by Rome III criteria (Rasquin 2006) | |
| Interventions | Intervention: mebeverine tablets, 135 mg twice daily, for a duration of 4 weeks Control: placebo | |
| Outcomes | Primary outcome: 2‐point reduction in FACES Pain Scale (scale 1 to 6) or report of "no pain" Secondary outcome: physician‐rated global severity and improvement using the Clinical Global Impression Severity and Improvement Scales (scale 1 to 7) Timing of outcome assessment: 12 weeks | |
| Notes | Study dates: 2013 Funding: The Isfahan University of Medical Sciences Conflicts of interest: none declared | |
| Risk of bias | ||
| Bias | Authors' judgement | Support for judgement |
| Random sequence generation (selection bias) | Low risk | Randomisation by computer‐generated random numbers in 4 blocks |
| Allocation concealment (selection bias) | Low risk | Authors state allocation was concealed. |
| Blinding of participants and personnel (performance bias) | Low risk | Authors state that the doctors, study participants, and study personnel assessing the outcomes were blinded. The drug codes for labelling the bottles were known only by the pharmacist. |
| Blinding of outcome assessment (detection bias) | Low risk | The primary outcome was self reported and therefore blinded. |
| Incomplete outcome data (attrition bias) | Low risk | The loss to follow‐up was equal between the 2 groups and was 28/115 (24%) of randomised participants, shown in flow diagram. |
| Selective reporting (reporting bias) | Low risk | All outcomes stated in the methods are reported. |
| Other bias | Low risk | 2 groups similar at baseline. Power calculation performed. No conflict of interest. Funded by an academic institution |
| Methods | Design: double‐blinded, placebo‐controlled, randomised trial of citalopram versus placebo Duration: 12 weeks | |
| Participants | Country: Iran Setting: paediatric gastroenterology outpatient clinic Sample size: 115 children (intervention 59, control 56) Gender: intervention group: 11 males, 32 females; control group: 19 males, 24 females (children who completed follow‐up) Mean age: intervention 10.4 years (SD 1.9 years); control 8.5 years (SD 2.2 years) for children who completed follow‐up Dropouts/withdrawals: 29 children (intervention 16, control 13) Diagnosis: functional abdominal pain, defined by Rome III criteria (Rasquin 2006) | |
| Interventions | Intervention: citalopram tablets 10 mg/day for the 1st week and then 20 mg/day for a total duration of 4 weeks Control: placebo | |
| Outcomes | Primary outcome: 2‐point reduction in FACES Pain Scale (scale 1 to 6) or report of "no pain" Secondary outcome: self rated depression, anxiety, and somatization scores Timing of outcome assessment: 12 weeks | |
| Notes | Study dates: 2013 Funding: The Isfahan University of Medical Sciences Conflicts of interest: none declared | |
| Risk of bias | ||
| Bias | Authors' judgement | Support for judgement |
| Random sequence generation (selection bias) | Low risk | Randomisation by computer‐generated random numbers in 4 blocks |
| Allocation concealment (selection bias) | Low risk | Authors state that allocation was concealed. |
| Blinding of participants and personnel (performance bias) | Low risk | Authors state that the doctors, study participants, and study personnel assessing the outcomes were blinded. The drug codes for labelling the bottles were known only by the pharmacist. |
| Blinding of outcome assessment (detection bias) | Low risk | The primary outcome was self reported and therefore blinded. |
| Incomplete outcome data (attrition bias) | Low risk | The loss to follow‐up was equal between the 2 groups and was 29/115 (25%) of randomised participants, shown in flow diagram. |
| Selective reporting (reporting bias) | Low risk | All outcomes stated in the methods are reported. |
| Other bias | Low risk | 2 groups similar at baseline, except for slight difference in age. Power calculation performed. No conflict of interest. Funded by an academic institution |
| Methods | Design: double‐blinded, placebo‐controlled, randomised trial Duration: 2 weeks | |
| Participants | Country: Iran Setting: paediatric gastroenterology clinic in Tehran Sample size: 36 children (included after dropouts 29 children: intervention 15, control 14) Gender: intervention: 7 boys, 8 girls; control: 5 boys, 9 girls Mean age: intervention 7.2 years (range 4.5 to 11 years); control 7.7 years (range 5 to 12 years) Dropouts/withdrawals: 7 (unclear from which group) Diagnosis: functional abdominal pain, defined by Rome II criteria (Rasquin‐Weber 1999) | |
| Interventions | Intervention: 0.25 to 0.5 mg/kg/day cyproheptadine in 2 divided doses for 2 weeks Control: placebo | |
| Outcomes |
Timing of outcome assessment: 2 weeks | |
| Notes | Study dates: 2006 to 2007 Funding: none declared Conflicts of interest: none declared | |
| Risk of bias | ||
| Bias | Authors' judgement | Support for judgement |
| Random sequence generation (selection bias) | Low risk | The authors state that the random allocation was performed using a randomised, quadruple order of A and B. |
| Allocation concealment (selection bias) | Low risk | The authors explain that the study personnel (research nurse and study physician) were blinded. This implies allocation concealment, as they did not know the group to which participants were allocated. |
| Blinding of participants and personnel (performance bias) | Low risk | The authors state that the placebo was similar. |
| Blinding of outcome assessment (detection bias) | Low risk | The participants were blinded and the outcome was self reported. |
| Incomplete outcome data (attrition bias) | Low risk | 36 participants were randomised. The authors state that 7 participants were excluded from the final analysis (5 for poor compliance and 2 for incomplete outcome data). We assume that they came equally from each group, as the included numbers of participants were 15 and 14 for the intervention and control groups, respectively (total 29). |
| Selective reporting (reporting bias) | Low risk | The primary outcome was reported. |
| Other bias | High risk | No power calculation was performed. The outcome was not measured by a validated tool. The sample size was small and the outcome was measured over a short time duration. There was no intention‐to‐treat analysis as the non‐compliant participants were excluded. |
| Methods | Design: double‐blinded, placebo‐controlled, randomised trial Duration: 4 weeks | |
| Participants | Country: USA Setting: 6 paediatric tertiary care hospitals, gastroenterology clinics Sample size: 90 children (intervention 46, control 44) Gender: 18 boys, 72 girls. Distribution between groups not given. Mean age: 12.7 years (range 8 to 17 years) Dropouts/withdrawals: 7 (3 from intervention group, 4 from control group) Diagnosis: functional abdominal pain, functional dyspepsia, or IBS, defined by Rome II criteria (Rasquin‐Weber 1999) | |
| Interventions | Intervention: 10 mg/day amitriptyline if weight < 35 kg, 20 mg/day amitriptyline if weight > 35 kg, for 4 weeks Control: placebo | |
| Outcomes |
Timing of outcome assessment: 4 weeks | |
| Notes | Study dates: 2003 to 2006 Funding: grant from American College of Gastroenterology and National Center for Research Resources, National Institutes of Health Conflicts of interest: none declared | |
| Risk of bias | ||
| Bias | Authors' judgement | Support for judgement |
| Random sequence generation (selection bias) | Unclear risk | The authors state that participants were randomised, but give no details of the method of randomisation. The 2 groups look similar at baseline, which suggests the method of randomisation was adequate. |
| Allocation concealment (selection bias) | Unclear risk | This concept is not mentioned in the paper. |
| Blinding of participants and personnel (performance bias) | Low risk | The authors state that participants and personnel were blinded. |
| Blinding of outcome assessment (detection bias) | Low risk | The outcomes are self and parent reported. The participants were blinded, and therefore so too was the outcome assessment. |
| Incomplete outcome data (attrition bias) | Low risk | 90 participants were included, of whom 83 completed the study, giving a 7.8% loss to follow‐up. |
| Selective reporting (reporting bias) | Low risk | All outcomes detailed in the methods were reported. |
| Other bias | High risk | The study was under‐recruited, as the power calculation stated that 120 participants were required, but only 90 were recruited. |
| Methods | Design: double‐blinded, placebo‐controlled, randomised, cross‐over trial Duration 6 weeks | |
| Participants | Country: USA Setting: tertiary paediatric hospital clinic at Mount Sinai Medical Center Sample size: 25 children (cross‐over trial so all participants received both interventions) Gender: 13 boys, 12 girls Mean age: 10.5 years (range 5.5 to 16.77 years) Dropouts/withdrawals: 1 participant, excluded after enrolment (as Giardia detected in stool) Diagnosis: RAP, defined by Apley's criteria (Apley 1958) | |
| Interventions | Intervention: 1 mg/kg/day famotidine in 2 divided doses for 3 weeks Control: placebo | |
| Outcomes |
Timing of outcome assessment: 3 weeks | |
| Notes | Study dates: 1998 Funding: none declared Conflicts of interest: none declared | |
| Risk of bias | ||
| Bias | Authors' judgement | Support for judgement |
| Random sequence generation (selection bias) | Unclear risk | The authors state that participants were randomised, but give no details of the method of randomisation. |
| Allocation concealment (selection bias) | Low risk | The authors do not mention allocation concealment, but they state that the study personnel were blinded, only the pharmacy was aware of allocation. We can therefore assume that at the point of randomisation, the study personnel did not know the treatment group to which each participant would be allocated. Outcomes were reported by children and parents, who were blinded to allocation. |
| Blinding of participants and personnel (performance bias) | Low risk | The authors state that both groups were blinded. |
| Blinding of outcome assessment (detection bias) | Low risk | The outcomes were self reported, and the participants were blinded. |
| Incomplete outcome data (attrition bias) | Low risk | The authors report that of the 26 children originally enrolled, 1 was excluded due to detection of Giardia. There were no further drops outs and therefore data were presented for 25 children. |
| Selective reporting (reporting bias) | Low risk | All outcomes mentioned in the methods were reported. |
| Other bias | High risk | No power calculation, small sample size, baseline data presented and the groups appear similar. The cross‐over trial had no washout period. The cross‐over trial varied according to response to the first treatment, which introduces bias as it is recognised that RAP is a condition that fluctuates over time. The raw data are not given, and we received no response from the authors to our request for this information. |
| Methods | Design: double‐blinded, placebo‐controlled, randomised trial Duration 4 months | |
| Participants | Country: UK Setting: hospital general paediatric clinic Sample size: 14 children Gender: not stated by authors Mean age: not reported (range 5 to 13 years) Dropouts/withdrawals: 2 Diagnosis: abdominal migraine = RAP (Apley 1958), with episodes associated with facial pallor, first‐degree relative with headaches | |
| Interventions | Intervention: 0.5 mg pizotifen syrup (0.25 mg/5 mL) in 2 divided doses per day. After 1 month the dose was increased to 0.75 mg/day if there had been no improvement. Control: placebo | |
| Outcomes |
Timing of outcome assessment: 4 months | |
| Notes | Study dates: 1995 Funding: none declared Conflicts of interest: none declared | |
| Risk of bias | ||
| Bias | Authors' judgement | Support for judgement |
| Random sequence generation (selection bias) | Low risk | From correspondence with the authors, it was established that the order for treatment allocation was both blinded and randomised. This was done in the hospital pharmacy, therefore the study personnel were also blinded. |
| Allocation concealment (selection bias) | Low risk | From correspondence with the authors, it was established that the randomisation was performed by the hospital pharmacy, and therefore the study personnel were also blinded. This implies there was allocation concealment. |
| Blinding of participants and personnel (performance bias) | Low risk | As explained above |
| Blinding of outcome assessment (detection bias) | Low risk | The outcomes were reported by parent and child, who were blinded. |
| Incomplete outcome data (attrition bias) | Low risk | 2 participants (14%) were excluded, as they had no outcome data. |
| Selective reporting (reporting bias) | Low risk | All outcomes mentioned in the methods were reported. |
| Other bias | High risk | No baseline data, no power calculation, no washout period for a cross‐over trial. The intervention was changed according to response; the authors stated that the medication was doubled if there was no response. The trial stopped early due to lack of drug supply. |
| Methods | Design: cross‐over, placebo‐controlled, randomised trial Duration: 5 weeks | |
| Participants | Country: USA Setting: hospital general paediatric clinic Sample size: 14 children Gender: intervention group (girls 58%; boys 5, girls 7), placebo group (girls 58%; boys 5, girls 7) Mean age: intervention group: 13.8 (+/‐ 1.6 years), placebo group: 13.8 (+/‐ 1.6 years) Dropouts/withdrawals: 2 Diagnosis: functional abdominal pain, according to Rome III criteria | |
| Interventions | Intervention: melatonin 5 mg (20 mL) at night, once daily for 14 days Control: placebo | |
| Outcomes |
Timing of outcome assessment: 2 weeks | |
| Notes | Study dates: not stated by authors, published in 2016 Funding: none declared Conflicts of interest: none declared | |
| Risk of bias | ||
| Bias | Authors' judgement | Support for judgement |
| Random sequence generation (selection bias) | Unclear risk | The authors state that participants were randomised, but give no details of the method of randomisation. |
| Allocation concealment (selection bias) | Low risk | Authors clearly state that parents were consented for the trial, and participant’s assent was obtained prior to study procedures, which implies that allocation concealment was achieved. |
| Blinding of participants and personnel (performance bias) | Low risk | Blinding explained, complete for participant and study team, the drug and placebo were labelled in pharmacy. |
| Blinding of outcome assessment (detection bias) | Low risk | The outcome assessment was self reported pain by the child, who was interviewed by the study team. Both the child and study team were blinded. |
| Incomplete outcome data (attrition bias) | Low risk | 14 enrolled, 12 completed the study; 14% dropout rate |
| Selective reporting (reporting bias) | Low risk | No evidence from the paper of outcomes that were not reported. |
| Other bias | High risk | Small study with no power calculation. This is a cross‐over study with no washout period. |
GI: gastrointestinal
IBS: irritable bowel syndrome
PedsQL: Pediatric Quality of Life Inventory
RAP: recurrent abdominal pain
SD: standard deviation
Characteristics of excluded studies [ordered by study ID]
Jump to:
| Study | Reason for exclusion |
| Ineligible study design | |
| Ineligible study design | |
| Ineligible study design | |
| Ineligible population | |
| Ineligible population | |
| Ineligible comparator | |
| Ineligible study design: literature review | |
| Ineligible population | |
| Ineligible population | |
| Ineligible comparator | |
| Ineligible population |
Risk of bias summary: review authors' judgements about each risk of bias item for each included study.
Risk of bias graph: review authors' judgements about each risk of bias item presented as percentages across all included studies.
| Antispasmodics compared to placebo for recurrent abdominal pain | ||||||
| Patient or population: school‐aged children (5 to 18 years of age) with recurrent abdominal pain Settings: hospital paediatric outpatient clinics Intervention: antispasmodic drugs Comparison: placebo | ||||||
| Outcomes | Illustrative comparative risks* (SD) | Relative effect (95% CI) | Number of participants | Quality of the evidence | Comments | |
| Assumed risk | Corresponding risk | |||||
| Placebo | Intervention | |||||
| Pain duration (mean pain duration, assessed at 4 weeks) | The mean duration of pain in the control group was 6.17 (± 11.61). | The mean duration of pain in the intervention group was51.6 (± 23.74). | MD ‐25.4 (‐35.5 to ‐15.3) | 120 (1) | ⊕⊝⊝⊝ | No evidence of efficacy |
| Pain improvement (clinician judged, assessed at 2 weeks) | 9 of 21 children in the control group had an improvement in pain. | 15 of 21 children in the intervention group had an improvement in pain. | OR 3.33 (0.93 to 12.01) | 42 (1) | ⊕⊝⊝⊝ | No evidence of efficacy |
| Pain frequency (episodes of pain in 4 weeks, assessed after 4 weeks) | The mean number of episodes of pain in the control group was 21.6 (32.4). | The mean number of episodes of pain in the intervention group was10.3 (14). | MD 11.3 (2.4 to 20.1) | 132 (1) | ⊕⊝⊝⊝ | No evidence of efficacy |
| Pain improvement (self reported response to treatment, assessed at 4 weeks) | The response to treatment in the control group was 30.3%. | The response to treatment in the intervention group was 40.6%. | OR 1.6 (0.7 to 3.4) | 115 (1) | ⊕⊕⊝⊝ | No evidence of efficacy |
| *The basis for the assumed risk (e.g., the median control group risk across studies) is provided in footnotes. The corresponding risk is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI). | ||||||
| GRADE Working Group grades of evidence | ||||||
| 1Downgraded for low methodological quality due to single, small study; risk of bias from incomplete outcome data and differential loss of participants between groups. The placebo differed in preparation and dose timing compared to the intervention drug. | ||||||
| Domain | 'Risk of bias' judgement | ||
| Low | High | Unclear | |
| Selection bias | |||
| Random sequence generation | If the study details any of the following methods: (1) simple randomisation (such as coin‐tossing, throwing dice, or dealing previously shuffled cards, a list of random numbers, or computer‐generated random numbers); or (2) restricted randomisation such as blocked, ideally with varying block sizes or stratified groups, provided that within‐group randomisation is not affected | If the study details no randomisation or an inadequate method such as alternation, assignment based on date of birth, case record number, and date of presentation. These latter methods may be referred to as ‘quasi‐random’. | If there is insufficient detail to judge the risk of bias
|
| Allocation concealment | If the study details concealed allocation sequence in sufficient detail to determine that allocations could not have been foreseen in advance of, or during, enrolment | If the study details a method where the allocation is known prior to assignment | If there is insufficient detail to judge the risk of bias |
| Performance bias | |||
| Blinding of participants and personnel | If the study details a method of blinding participants and personnel. Detail would need to be sufficient to show that participants and personnel were unable to identify the therapeutic intervention from the control intervention. | If the methods detail that the participants or study personnel were not blinded to the study medication or placebo | If there is insufficient detail to judge the risk of bias |
| Detection bias | |||
| Blinding of outcome assessment | If the study details a blinded outcome assessment. This may only be possible for outcomes that are externally assessed. | If the outcome assessment is not blinded. We expect this may be unavoidable for self rated outcomes of unblinded interventions. | If there is insufficient detail to judge the risk of bias
|
| Attrition bias | |||
| Incomplete outcome data | If the study reports attrition and exclusions, including the numbers in each intervention group (compared with total randomised participants), reasons for attrition or exclusions, and any re‐inclusions; the impact of missing data is not believed to have altered the conclusions; and reasons for the missing data are acceptable | We may judge the risk of attrition bias to be high due to the amount, nature, or handling (such as per‐protocol analysis) of incomplete outcome data. | If there is insufficient detail to judge the risk of bias, e.g. if the number of children randomised to each treatment is not reported |
| Reporting bias | |||
| Selective reporting | If there is complete reporting of all outcome data. This will be determined based on comparison of the protocol and published study, if available. | If the reporting is selective so that some outcome data are not reported | If there is insufficient detail to judge the risk of bias, e.g. protocols are unavailable |
| Other sources of bias | |||
| Other bias | If the study is judged to be at low of risk of other potential sources of bias, such as no differential loss to follow‐up or an adequate washout period in cross‐over trials | If there are other sources of bias, such as differential loss to follow‐up or an inadequate washout period in cross‐over trials | If there is insufficient detail to judge the risk of bias |
