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Drug treatment for faecal incontinence in adults

  1. Muhammad Imran Omar*,
  2. Cameron Edwin Alexander

Editorial Group: Cochrane Incontinence Group

Published Online: 11 JUN 2013

Assessed as up-to-date: 21 JUN 2012

DOI: 10.1002/14651858.CD002116.pub2


How to Cite

Omar MI, Alexander CE. Drug treatment for faecal incontinence in adults. Cochrane Database of Systematic Reviews 2013, Issue 6. Art. No.: CD002116. DOI: 10.1002/14651858.CD002116.pub2.

Author Information

  1. University of Aberdeen, Academic Urology Unit, Aberdeen, Scotland, UK

*Muhammad Imran Omar, Academic Urology Unit, University of Aberdeen, Health Sciences Building (second floor), Foresterhill, Aberdeen, Scotland, AB25 2ZD, UK. m.i.omar@abdn.ac.uk. drimran@yahoo.com.

Publication History

  1. Publication Status: New search for studies and content updated (no change to conclusions)
  2. Published Online: 11 JUN 2013

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Characteristics of included studies [ordered by study ID]
Carapeti 2000a #

Methods Cross-over randomised controlled trial


Participants36 adults (22 women) with passive FI and structurally intact anal sphincters
Mean age 58 years (range 28 to 81)
Mean duration of faecal incontinence: 5 years (SD 4)
Characteristics of patients were comparable at baseline
Exclusion criteria: disruption of anal sphincter muscle on endoanal ultrasound examination, concomitant use of tricyclic or mono-amine oxidase inhibitors, hypertension, aortic aneurysm or ischaemic heart disease, pregnancy, inflammatory bowel disease and surgically repairable sphincter damage.


InterventionsA: 10% phenylephrine gel
B: placebo gel (0.5 mL), both used anally twice a day
Length of treatment: 4 weeks (two four-week treatment periods with a one-week washout period)
Dose titration: the choice of 10% phenylephrine gel was based on previous pilot studies on healthy volunteers


OutcomesSubjective cure: A: 0/36, B: 0/36
Subjective improvement in symptoms: A: 6/36, B: 2/36 [A: 28% versus B: 9% at the end of the first trial period]
Incontinence score (n, mean, SD): A: 18, 12.5 (3.4), B: 18, 12.6 (4.2) (no difference)
Adverse effects: A: 3/36, B: 0/36 (localised mild dermatitis, settled when drug stopped)
Maximum anal resting pressure (n, mean, SD): A: 18, 65 (21), B: 18, 54 (21) (no difference)
Anodermal blood flow (no change)


Notes15 patients continued with loperamide during the study
Sample size calculation pre-stated (16 patients required)
Suggestion of an interaction between treatment and placebo periods, possibly reflecting an insufficient washout period


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Low risk"Randomisation was carried out by a pharmacist by means of computer generated random numbers"

Allocation concealment (selection bias)Low risk"The randomization code was kept in the hospital pharmacy and made known to the investigators only after analysis of the completed study."

Blinding of participants and personnel (performance bias)
All outcomes
Unclear riskRepored as "double-blind" trial but it is not specified who was blinded.

Blinding of outcome assessment (detection bias)
All outcomes
Unclear riskRepored as "double-blind" trial but it is not specified who was blinded.

Incomplete outcome data (attrition bias)
All outcomes
Low riskNo incomplete data

Selective reporting (reporting bias)Unclear riskProtocol not available

Was use of a cross over design appropriate?Low riskYes

Is it clear that the order of receiving treatment was randomised?Low riskUsed computer-generated random numbers.

Can it be assumed that the trial was not biased from carry over effects?Unclear risk"4 weeks treatment periods separated by a 1 week washout period"

Carapeti 2000b #

MethodsCross-over randomised controlled trial


Participants12 adults (7 women) with FI after ileoanal pouch surgery for ulcerative colitis
Median age 44 years (range 29 to 67)
8 had nocturnal incontinence only, 4 had both diurnal and nocturnal incontinence
Exclusion criteria: active pouchitis, disruption of anal sphincter muscles on endoanal ultrasound examination, concomitant use of tricyclic or monoamine oxidase inhibitors, hypertension, ischaemic heart disease or aortic aneurysm.


InterventionsA: 10% phenylephrine gel
B: placebo gel (0.5 mL), both used anally twice a day
Length of treatment: 4 weeks (two four-week treatment periods with a one-week washout period)
Dose titration: the choice of 10% phenylephrine gel was based on previous pilot studies on healthy volunteers


OutcomesCure: A: 4/12, B: 0/12
Subjective improvement in symptoms: A: 6/12, B: 1/12
Incontinence score (28 day symptom score, n, mean, SD): A: 12, 12.2 (5.7), B: 12, 16.5 (4.4)
Adverse effects: A: 0/12, B: 0/12
Maximum anal resting pressure (n, mean, SD): A: 12, 89 (17), B: 12, 75 (14)
Anodermal blood flow (no difference)


Notes8 patients continued with loperamide during the study
Suggestion of an interaction between treatment and placebo periods, possibly reflecting an insufficient washout period


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Low risk"Random assignment was performed using random numbers generated by a scientific calculator, and the randomization code was kept in the hospital pharmacy and made known to the investigators only after analysis of the completed study"

Allocation concealment (selection bias)Low risk"Random assignment was performed using random numbers generated by a scientific calculator, and the randomization code was kept in the hospital pharmacy and made known to the investigators only after analysis of the completed study"

Blinding of participants and personnel (performance bias)
All outcomes
Unclear riskRepored as "double-blind" trial but it is not specified who was blinded.

Blinding of outcome assessment (detection bias)
All outcomes
Unclear riskRepored as "double-blind" trial but it is not specified who was blinded.

Incomplete outcome data (attrition bias)
All outcomes
Low riskNo incomplete data

Selective reporting (reporting bias)Unclear riskProtocol not available

Was use of a cross over design appropriate?Low riskYes

Is it clear that the order of receiving treatment was randomised?Low risk"Random assignment was performed using random numbers generated by a scientific calculator, and the randomization code was kept in the hospital pharmacy and made known to the investigators only after analysis of the completed study"

Can it be assumed that the trial was not biased from carry over effects?Unclear risk"...........two four-week treatment phases separated by a one-week washout phase."

Chassagne 2000

MethodsRandomised controlled trial


Participants206 people (145 women) with at least weekly faecal incontinence associated with chronic rectal emptying (40% of patients had daily faecal incontinence for more than 2 years). 178 were available for analysis after the first week of treatment. Patients were aged 65 years or older and residents of long-term care units.
Mean age: 85.3 years
Characteristics of patients were comparable at baseline but not given after losses to follow-up


InterventionsA: 30 g per day of a single osmotic laxative (lactulose)
B: 30 g of an osmotic laxative (lactulose), along with daily glycerine suppository and a tap-water enema once a week
Length of treatment: 8 weeks
Dose titration: no


OutcomesMean number of FI episodes per week (n, mean, SD): A: 61, 6 (2.9), B: 62, 6 (2.7) (P = 0.9 after 4 weeks)
Mean number of bedding and/or clothing changes per week (n, mean, SD): A: 61, 20 (4), B: 62, 19.5 (5.2) (P = 0.55 after 4 weeks)
Incidents of FI per day per participant: A: 0.85, B: 0.84
Incidents of soiled laundry per day per participant: A: 2.9, B: 2.8
Adverse effects: not reported.


NotesHigher dropout rate in Group I than in Group II
Results not clearly reported
Number of 'responders' and 'non-responders' were assessed only in Group II
No differences in subgroup analyses according to cognitive or mobility impairment, or between centres


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Unclear riskReported as "prospective randomized study" but the method of sequence generation not specified

Allocation concealment (selection bias)Unclear riskReported as "prospective randomized study" and it is not specified whether or not the allocation was concealed.

Blinding of participants and personnel (performance bias)
All outcomes
High risk"This study could be randomized but not blinded because outcomes were measured daily and because the treatment was provided by the nursing staff."

Blinding of outcome assessment (detection bias)
All outcomes
High risk"This study could be randomized but not blinded because outcomes were measured daily and because the treatment was provided by the nursing staff."

Incomplete outcome data (attrition bias)
All outcomes
Unclear riskNo missing data, however 32 participants in Group I and 23 participants in Group II withdrew from the trial.

Selective reporting (reporting bias)Unclear riskProtocol not available

Was use of a cross over design appropriate?Low riskThis is a randomised controlled trial and not a cross-over trial and this domain of risk of bias assessment is not applicable and would be judged as low risk.

Is it clear that the order of receiving treatment was randomised?Low riskThis is a randomised controlled trial and not a cross-over trial and this domain of risk of bias assessment is not applicable and would be judged as low risk.

Can it be assumed that the trial was not biased from carry over effects?Low riskThis is a randomised controlled trial and not a cross-over trial and this domain of risk of bias assessment is not applicable and would be judged as low risk.

Cheetham 2001 #

MethodsRandomised controlled trial.


Participants10 people (7 women) with passive faecal incontinence and low maximal resting anal pressure but with intact sphincters demonstrated on endoanal ultrasound scan
Median duration of incontinence: 2 years (range 1 to 7)
Groups comparable at baseline on maximal resting anal pressure (cross-over)
Exclusion criteria: pregnant women, ischaemic heart disease, aortic aneurysm, uncontrolled hypertension, inflammatory bowel disease, other secondary causes of FI


InterventionsA: 0% gel (placebo containing no active ingredient)
B: 10% phenylephrine gel in identical coded foil tubes
C: 20% phenylephrine gel
D: 30% phenylephrine gel
E: 40% phenylephrine gel
Duration of treatment: 1 anal application per day, minimum 48 hours apart
Assessment: one and two hours after application


OutcomesMaximal resting anal pressure: comparable at baseline on all study days
Maximal resting anal pressure: 7 increased, no change in 3 participants
D & E: maximal resting anal pressure increased to within normal range (P < 0.05 versus placebo group A)
B & C: maximal resting anal pressure increased but below normal range
Effect sustained for a median of 7 hours
Adverse effects: two people experienced a stinging/burning sensation immediately after application of phenylephrine gel, which settled within 20 minutes


NotesWashout of 48 hours between daily doses


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Unclear riskIt is reported that "Gels were applied in a random order..................." however it is not specified how sequence was generated

Allocation concealment (selection bias)Unclear riskIt is reported that "Gels were applied in a random order..................." however it is not specified if the allocation was concealed or no

Blinding of participants and personnel (performance bias)
All outcomes
Low riskIt is reported that both the investigator and patients were unaware of the nature of each gel.

Blinding of outcome assessment (detection bias)
All outcomes
Unclear riskIt is not specified if the outcome was assessed by the investigator or someone else.

Incomplete outcome data (attrition bias)
All outcomes
Low riskNo missing data

Selective reporting (reporting bias)Unclear riskProtocol not available

Was use of a cross over design appropriate?Low riskThis is a randomised controlled trial and not a cross-over trial and this domain of risk of bias assessment is not applicable and would be judged as low risk.

Is it clear that the order of receiving treatment was randomised?Low riskThis is a randomised controlled trial and not a cross-over trial and this domain of risk of bias assessment is not applicable and would be judged as low risk.

Can it be assumed that the trial was not biased from carry over effects?Low riskThis is a randomised controlled trial and not a cross-over trial and this domain of risk of bias assessment is not applicable and would be judged as low risk.

Cohen 2001 #

MethodsCross-over randomised controlled trial


Participants11 adults
Dropouts: 1 (diarrhoea on placebo, as participants had to stop normal anti-diarrhoeal drugs)
Inclusion: patients with ileoanal pouches (9 J, 2 W) 9 to 48 months after ileostomy closure (median 27); 8 for ulcerative colitis, 2 for familial adenomatous polyposis; 8 men, 3 women
Exclusion: not specified
Age: 23 to 50 years (median 38)


InterventionsInitial 2 day drug-free washout period
A (10): loperamide oral capsules 4 mg 3x/day and placebo suppositories for 5 days in first 4 participants, then for 7 days in the remaining 6
Washout phase with placebo oral and suppository treatment between first and second arms
B (10): loperamide suppositories 2 mg x3 in hard fat and placebo oral capsules


OutcomesMean stool frequency stated to be significantly lower with oral loperamide (Group A) compared with suppository (Group B, P < 0.02) or placebo washout phase (P < 0.05)
No significant difference between suppository (Group B) or placebo washout phases


NotesNo useable data (graphical form only)


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Unclear riskIt is reported that the "Subjects were randomized........", however, method of sequence generation not specified.

Allocation concealment (selection bias)Unclear riskNot specified

Blinding of participants and personnel (performance bias)
All outcomes
Low risk"Subjects were blinded to the contents of their medication in all three phases. The investigators were blinded to the contents in the first and third phases."

Blinding of outcome assessment (detection bias)
All outcomes
Unclear riskNot reported

Incomplete outcome data (attrition bias)
All outcomes
Low riskNo incomplete data

Selective reporting (reporting bias)Unclear riskProtocol not available

Was use of a cross over design appropriate?Low riskThe design seems to be appropriate, however information pertaining to sequence generation and allocation concealment are not provided, and the washout period seems to be short.

Is it clear that the order of receiving treatment was randomised?Unclear riskNot specified

Can it be assumed that the trial was not biased from carry over effects?High risk"2-day drug-free washout period"

Fox 2005 #

MethodsCross-over randomised controlled trial.


Participants10 adults (7 men and 3 woman)
Dropouts:
Inclusion: obese people on orlistat 120 mg 3x/day; BMI > 30; negative pregnancy test
Exclusion: elderly (age > 55 years); postnatal women; continence problems; gastrointestinal disease; psychological problems; abnormal laboratory results
Age: mean 46 years (range 27 to 54)
BMI: 35.7 (30.2 to 43.6)


InterventionsA: loperamide 2 mg + placebo x 2
B: loperamide 2 mg x2 (= 4 mg) + placebo x 1
C: loperamide 2 mg x3 (= 6 mg) + no placebo
Each block of active treatment for 2 weeks
Washout: 2 weeks between each block


OutcomesNo effect on stool frequency
Trend for increased stool consistency from median (IQR) score 0.7 (0.5 to 0.9) with placebo to 0.4 (0.3 to 0.6) with 6 mg dose (0 = all hard, 1 = all liquid)
Continence problems (fecal spotting and incontinence) reduced with loperamide vs placebo, P < 0.05
Significant positive dose-response relationship with increasing dose of loperamide (reduced FI with 2 mg dose, and almost no FI with 4 mg and 6 mg doses)
Adverse effects: none (specifically no severe constipation with the highest doses)


NotesStudy aim was to reduce the adverse effects of orlistat treatment for obesity (oily stools, increased faecal frequency and urgency and 'fecal spotting' (= faecal incontinence) in order to increase compliance with orlistat
No useable data


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Low risk"The hospital pharmacy dispensed medication according to a computer generated randomization list."

Allocation concealment (selection bias)Low risk"The sequence was concealed until the study was completed".

Blinding of participants and personnel (performance bias)
All outcomes
Unclear riskReported as "double-blind study", however it is not specified who was blinded.

Blinding of outcome assessment (detection bias)
All outcomes
Unclear riskReported as "double-blind study", however it is not specified who was blinded.

Incomplete outcome data (attrition bias)
All outcomes
Low riskNo incomplete outcome data

Selective reporting (reporting bias)Unclear riskProtocol not available

Was use of a cross over design appropriate?Low riskEach participant received placebo and two of the three doses of loperamide for 2 weeks, each separated by a 2-week washout. The sequence was concealed until the study was completed.

Is it clear that the order of receiving treatment was randomised?Low risk"The hospital pharmacy dispensed medication according to a computer generated randomization list."

Can it be assumed that the trial was not biased from carry over effects?Low riskEach participant received placebo and two of the three doses of loperamide for 2 weeks, each separated by a 2-week washout.

Hallgren 1994 #

MethodsCross-over randomised controlled trial.


Participants30 adults (8 women) with ileoanal pouches (16 handsewn and 14 stapled), performed for ulcerative colitis. Groups combined for analysis
Median age: 38 years (range 26 to 61)
Exclusion criteria: not specified


InterventionsA: loperamide 4 mg three times a day
B: placebo
Duration of treatment: 8 day treatment periods with 7 day washout period.
Dose titration: no


OutcomesNumber experiencing soiling, day: A: 3/28, B: 7/28; night: A: 1/28, B: 11/28
Number using pads, day: A: 1/28, B: 3/28; night: A: 1/28, B: 6/28
Defecation frequency (n, mean, SD): A: 28, 4.24 (1.86), B: 28, 6.43 (1.99)
Anal canal resting pressure, mm Hg (n, mean, SD): A: 28, 62 (16), B: 28, 55 (9)
Anal canal maximum squeeze pressure, mm Hg, (n, mean, SD): A: 28, 223 (82), B: 28, 219 (93)
Pouch volumetry and contractility.
Sensory threshold, rectal balloon distension, cm water, for 'sensation of filling' and 'defecation urge' (n, mean, SD): A: 28, 30 (12), B: 28, 27 (15)
Recto/pouch - anal reflex inhibition on distension.
No adverse effects.


NotesPatients were asked to keep to usual meal times and diet.
Data from two groups combined, and converted from medians and 95% CIs to means and SDs.


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Unclear riskNot specified

Allocation concealment (selection bias)Unclear riskNot specified

Blinding of participants and personnel (performance bias)
All outcomes
Low riskReported as "double blinded" and used "identical capsule" therefore participants must be blinded. Not sure about personnel

Blinding of outcome assessment (detection bias)
All outcomes
Unclear riskNot reported

Incomplete outcome data (attrition bias)
All outcomes
Low riskNo complete data

Selective reporting (reporting bias)Unclear riskProtocol not available

Was use of a cross over design appropriate?Low riskSeems appropriate with seven days washout period in between.

Is it clear that the order of receiving treatment was randomised?Unclear riskMethod of randomisation not specified

Can it be assumed that the trial was not biased from carry over effects?Low riskThere was seven days washout period

Harford 1980 #

MethodsCross-over randomised controlled trial


Participants15 people (14 women) with chronic diarrhoea and FI
Range of severity of FI: once a day to once a month
Mixed aetiology of diarrhoea
Age: 31 to 70 years
Exclusion criteria: none specified


InterventionsA: diphenoxylate (2.5 mg) plus atropine sulfate (25 mcg)
B: placebo
Length of treatment: 3 days, with one day of washout
Dose: 1 or 2 tablets, four times a day
Dose titration: not clearly reported. The first four patients were treated with two tablets every six hours (standard treatment). However, the 4th patient experienced abdominal pain and the dose was reduced in subsequent patients from 2 to 1 tablet every six hours.


OutcomesFailure rate (number not continent): A: 0/15, B: 3/15
Failure to improve (in stool weight and frequency): A: 3/15, B: 3/15
Stool frequency (n, mean, SD): A: 15, 2.6 (2.7), B: 15, 4.9 (3.1)
Stool weight (n, mean, SD): A: 15, 256 (333), B: 460 (150)
Anal canal resting pressure, mm Hg (n, mean, SD): A: 15, 41 (23), B: 15, 39 (19)
Anal canal maximum squeeze pressure, mm Hg, (n, mean, SD): A: 15, 94 (68), B: 15, 96 (68)
Duration of squeeze, seconds, (n, mean, SD): A: 15, 87 (128), B: 15, 86 (128)
Sensory threshold, rectal balloon distension, cm water: 15, 12 (12), B: 15, 31 (62)
Saline retention (continence) test, mL water: A: 15, 492 (461), B: 15, 486 (445)
Adverse effects: not reported.


NotesPatients were admitted to hospital and given a standardised diet


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Unclear riskReported as "patients were randomized in a double-blind fashion", however method of sequence generation not specified.

Allocation concealment (selection bias)Unclear riskNot specified.

Blinding of participants and personnel (performance bias)
All outcomes
Low risk"Neither the patients, the laboratory personnel, nor the physicians in charge knew when the patients were lomotil or when they were on placebo until the code was broken after the experiment was completed".

Blinding of outcome assessment (detection bias)
All outcomes
Low risk"Neither the patients, the laboratory personnel, nor the physicians in charge knew when the patients were lomotil or when they were on placebo until the code was broken after the experiment was completed".

Incomplete outcome data (attrition bias)
All outcomes
High riskreported data of only those participants who completed the trial as reported "data on this 4th patient are not included ion this paper...........". The excluded patient had "severe abdominal discomfort" the cause of which is not specified.

Selective reporting (reporting bias)Unclear riskProtocol not available

Was use of a cross over design appropriate?Low riskSeems appropriate

Is it clear that the order of receiving treatment was randomised?Unclear riskNot specified

Can it be assumed that the trial was not biased from carry over effects?High riskNo washout period

Kusunoki 1990 #

MethodsCross-over randomised controlled trial


Participants17 patients (4 women) with 'J' configuration ileoanal pouches 1 to 4 months after closure of diverting ileostomy (8 patients with ulcerative colitis and 9 with familial adenomatous polyposis)
Mean age 34 years (range 21 to 45, SD 6.51)
Exclusion criteria: none specified


InterventionsA: sodium valproate 400 mg
B: placebo
Dose: four times a day
Length of treatment: two one-week treatment periods with a three day washout period
Dose titration: no


OutcomesNumber with FI (soiling): A: 3/17, B: 10/17
Stool frequency (n, mean SD): A: 17, 5.98 (2.97), B: 17, 9.65 (4.1)
Adverse effects: A: 6 people experienced nausea and 2 abdominal pain (8/17), B: 0/17
Perianal skin irritation due to contact with faeces: A:3/17, B: 9/17
Anal canal resting pressure, mm Hg (n, mean, SD) (at 7 days): A: 17, 63.6 (12.4), B: 17, 42.5 (8.9)
Anal canal motility (amplitude, frequency and voluntary contractions)


NotesSodium valproate has contractile effects on the internal anal sphincter
Patients ate a controlled hospital diet and took no other drugs


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Unclear riskNot specified. Reported as "The valproate sodium and placebo series were carried out in random order"

Allocation concealment (selection bias)Unclear riskNot specified

Blinding of participants and personnel (performance bias)
All outcomes
Unclear riskNot specified

Blinding of outcome assessment (detection bias)
All outcomes
Unclear riskNot specified

Incomplete outcome data (attrition bias)
All outcomes
Low riskNo incomplete data

Selective reporting (reporting bias)Unclear riskProtocol not assessed

Was use of a cross over design appropriate?Unclear riskSeems appropriate

Is it clear that the order of receiving treatment was randomised?Unclear riskNot specified

Can it be assumed that the trial was not biased from carry over effects?Low riskThere was a 3-day washout period

Lumi 2009

MethodsRandomised controlled trial


ParticipantsAdults patients > 21 years old who, having undergone coloproctectomy with ileoanal anastomosis and J-shaped ileal reservoir, presented with nocturnal faecal incontinence

Exclusion criteria: associated anal pathology, active pouchitis, stenotic ileoanal anastomosis, concomitant treatment with loperamide, monoaminoxidase inhibitors and/or tricyclic antidepressants, pregnancy, narrow angle glaucoma, uncontrolled arterial hypertension/coronary disease/cardiac arrhythmias/aortic aneurysm, epilepsy

37 patients initially identified from 98 interviews

Reasons for non - inclusion/withdrawal: 9 with associated anal pathology or intercurrent illness, 9 did not complete previous evaluations, 4 refused to participate, 3 did not complete treatment

12 participants included in final analysis

Group A: 5 (2 men, 3 women. Mean age: 49.0 [Range 27-62])

Group B: 7 (6 men,1 woman. Mean age: 38.7 [Range: 24-63])


InterventionsA: Cream with active ingredient (10% phenylephrine)

B: Placebo cream

0.5 mg cream to be applied digitally around anal margin by patients before going to bed

Length of treatment: 1 month (number of days unclear). A faecal incontinence diary was kept for 21 days before treatment and during the treatment month.

All patients received 3.5g Plantago ovata thereby guaranteeing minimal fibre intake. Liquid intake restricted to 1.5 L/day


OutcomesOccurence of faecal incontinence during treatment; median (range)

Group A: 5.4 (0-14) Group B: 9 (0-19)


Notes9 patients with ulcerative colitis (Group A; 5 Group B; 4,). 3 patients previously operated for Familial Adenomatous Polyposis (all Group B). Inconsistent with exclusion criteria of the trial (associated anal pathology).

Discrepancy between text and table: texts states 3 men in group A whereas table states 2 men


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Unclear risk'Fueron randomizados en dos grupos (A) y (B), utilizando la técnica de muestreo en bloque'

'They were randomised into two groups (A) and (B), using the technique of block sampling'

Allocation concealment (selection bias)Unclear riskNone mentioned

Blinding of participants and personnel (performance bias)
All outcomes
Unclear riskTechnique not mentioned

Blinding of outcome assessment (detection bias)
All outcomes
Unclear riskTechnique not mentioned

Incomplete outcome data (attrition bias)
All outcomes
High riskTwo participants in Group B and 1 in Group A did not complete treatment, these results were not included in final analysis

Selective reporting (reporting bias)High riskResults of two participants not completing trial not reported

Was use of a cross over design appropriate?Low riskThis is a randomised controlled trial and not a cross-over trial and this domain of 'Risk of bias' assessment is not applicable and would be judged as low risk.

Is it clear that the order of receiving treatment was randomised?Low riskThis is a randomised controlled trial and not a cross-over trial and this domain of 'Risk of bias' assessment is not applicable and would be judged as low risk.

Can it be assumed that the trial was not biased from carry over effects?Low riskThis is a randomised controlled trial and not a cross-over trial and this domain of 'Risk of bias' assessment is not applicable and would be judged as low risk.

Palmer 1980 #

MethodsCross-over randomised controlled trial (three arms)


Participants30 patients with persistent (chronic) diarrhoea for at least 3 months (definition of diarrhoea included urgency and faecal incontinence). Diagnoses included irritable bowel, Crohn's disease, after gastric surgery, ulcerative colitis, diabetes
Daily stool frequency at baseline: 4.9 (SEM 0.4) (range 1 to 9 times)
Previous treatment: codeine (5); loperamide (10); diphenoxylate (2)


InterventionsA: loperamide hydrochloride (2 mg)
B: codeine phosphate (45 mg)
C: diphenoxylate (5 mg) with atropine sulfate (0.025 mg)
Length of treatment: each drug for 4 weeks


OutcomesNumber of people with FI: A: 2/25, B: 3/25, C: 6/25
Per cent of stools that were solid: A: 68%, B: 58%, C: 36% (P < 0.01)
Stool frequency (n, mean, SEM): A: 15, 1.8 (0.3), B: 15, 1.9 (0.3), C: 15, 1.9 (0.3)
Faecal urgency: A: 3/16, B: 4/17, C: 9/17 (P < 0.05 for C versus A and B)
Adverse effects (abdominal pain, central effects, headache): A: 22 in 10/25 participants, B: 29 in 12/25, C: 39 in 12/25 (P < 0.05 for A versus C)
Adverse effects causing withdrawal from one arm (poor control, abdominal pain, vomiting, unwell, constipation): A: 4/25, B: 4/25, C: 5/25
Preference for treatment: A: 8/25, B: 7/25, C: 5/25, no preference 5/25


NotesNot clear how many patients suffered from faecal incontinence at baseline.
Patients were instructed to increase the daily dose gradually until control was achieved or side effects became intolerable (but outcomes from last 3 weeks of treatment, after treatment stabilised)
Pre-trial and between-treatments washout periods were not included because of the relatively short half-life of the drugs used and patients would not be able to tolerate a drug-free week


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Unclear riskNot specified

Allocation concealment (selection bias)Unclear riskNot specified

Blinding of participants and personnel (performance bias)
All outcomes
Low riskReported as "double blinded" and used "identical capsule" therefore participants must be blinded. Not sure about personnel

Blinding of outcome assessment (detection bias)
All outcomes
Unclear riskNot specified

Incomplete outcome data (attrition bias)
All outcomes
High risk5 patients failed to attend the clinic regularly and withdrew early in the study. Ten further patients out of remaining 25 patients failed to complete the treatment period for one or more drugs

Selective reporting (reporting bias)Unclear riskProtocol not available

Was use of a cross over design appropriate?Low riskSeems appropriate

Is it clear that the order of receiving treatment was randomised?Unclear riskNot stated

Can it be assumed that the trial was not biased from carry over effects?High riskPatients were instructed to increase the daily dose gradually until control was achieved or side effects became intolerable (but outcomes from last 3 weeks of treatment, after treatment stabilised)
Pre-trial and between-treatments washout periods were not included because of the relatively short half-life of the drugs used and patients would not be able to tolerate a drug-free week

Park 2007

MethodsRandomised controlled trial


Participants35 patients with low anterior resection with rectal cancer were recruited. 6 participants withdrew and the results were reported of 29 participants; 17 in the treatment group and 12 in the placebo group.All participants had anal incontinence of solid or liquid stools or gas and experienced failure of other treatments with anti-diarrhoeal agents or biofeedback

Exclusion criteria were pregnancy, Ischaemic heart disease, uncontrolled hypertension, aortic aneurysm, treatment with monoamine oxidase inhibitors or tricyclic antidepressants, surgically reparable external sphincter injury, inflammatory bowel disease, or any other
disorder known to cause secondary anal incontinence.


InterventionsA: 30% Phenylephrine (3 g of Phenylephrine HCl in 7 g of white petrolatum) gel

B: Identical placebo gel

Length of treatment: 0.5 mL of gel was applied topically to the anal margin twice daily for 4 weeks,


OutcomesAnal incontinence evaluated with Faecal Incontinence Severity Index (FISI)

A (n = 17)= Baseline: 32.5(14.5); After: 32.3(14.7) P = 0.940

B (n = 12)= Baseline: 32.1 (11.2); After: 32.4(14.4) P = 0.626

Quality of life assessed with Faecal Incontinence Quality of life (FIQL) scale and included the following domains: lifestyle, coping, depression and embarrassment

Lifestyle:

A (n = 17)= Baseline: 2.9(0.8); After: 2.9(1.0) P = 0.801

B (n = 12)= Baseline: 2.7(0.5); After: 3.0(0.8) P = 0.269

Coping:

A (n = 17)= Baseline: 2.5(0.9); After: 2.8(0.9) P = 0.110

B (n = 12)= Baseline: 2.5(0.5); After: 2.8(0.5) P = 0.119

Depression:

A (n = 17)= Baseline: 3.2(0.7); After: 3.2(0.8) P = 0.415

B (n = 12)= Baseline: 3.1(0.5); After: 3.2(0.5) P = 0.554

Embarrassment:

A (n = 17)= Baseline: 2.7(0.7); After: 3.0(0.7) P = 0.090

B (n = 12)= Baseline: 2.7(0.6); After: 2.6(0.8) P = 0.855

Manometry:

Resting pressure (mmHg):

A (n = 17)= Baseline: 30.0(12.3); After: 27.3(12.7) P = 0.362

B (n = 12)= Baseline: 32.6(14.2); After: 27.2(15.0) P = 0.306

Squeezing pressure (mmHg):

A (n = 17)= Baseline: 143.3(60.5); After: 160.4(76.9) P = 0.083

B (n = 12)= Baseline: 152.6(86.5); After: 147.1(76.5) P = 0.625

Sustained duration (s):

A (n = 17)= Baseline: 41.9(24.5); After: 44.9(48.3) P = 0.848

B (n = 12)= Baseline: 39.6(24.4); After: 32.8(14.4) P = 0.187

Sphincter length (cm):

A (n = 17)= Baseline: 3.2(0.9); After: 3.4(0.8) P = 0.368

B (n = 12)= Baseline: 3.5(0.8); After: 3.4(0.8) P = 0.743

High pressure zone (cm):

A (n = 17)= Baseline: 2.4(2.1); After: 1.9(0.5) P = 0.378

B (n = 12)= Baseline: 2.1(0.9); After: 2.3(0.9) P = 0.556

Complications:

Dermatitis reaction: A = 5/17; B = 1/12

Palpitation: A = 0/17; B = 1/12

Headache: A = 2/17; B = 0/12


NotesNot clear how many patients suffered from faecal incontinence at baseline.
Patients were instructed to increase the daily dose gradually until control was achieved or side effects became intolerable (but outcomes from last 3 weeks of treatment, after treatment stabilised)
Pre-trial and between-treatments washout periods were not included because of the relatively short half-life of the drugs used and patients would not be able to tolerate a drug-free week


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Low risk"A one-to-one randomization code was derived by the pharmacy trials coordinator using a computer-generated random number sequence"

Allocation concealment (selection bias)Low risk"The randomization code was kept in the hospital pharmacy and made known to the investigators only after the study was completed".

Blinding of participants and personnel (performance bias)
All outcomes
Low riskIt is mentioned that the trial was "double blind" and it is also reported that "The placebo and phenylephrine gel were identical in appearance and texture and were supplied in identical containers" therefore it seems that the participants and personnel must be blinded although not specifically stated.

Blinding of outcome assessment (detection bias)
All outcomes
Unclear riskNot specified

Incomplete outcome data (attrition bias)
All outcomes
Unclear riskNo incomplete data although 6 participants (2 from the intervention and 4 from the placebo arm) withdrew from the study due to poor compliance

Selective reporting (reporting bias)Unclear riskProtocol not available.

Was use of a cross over design appropriate?Low riskThis is a randomised controlled trial and not a cross-over trial and this domain of risk of bias assessment is not applicable and would be judged as low risk.

Is it clear that the order of receiving treatment was randomised?Low riskThis is a randomised controlled trial and not a cross-over trial and this domain of risk of bias assessment is not applicable and would be judged as low risk.

Can it be assumed that the trial was not biased from carry over effects?Low riskThis is a randomised controlled trial and not a cross-over trial and this domain of risk of bias assessment is not applicable and would be judged as low risk.

Pinedo 2012

MethodsRandomised controlled trial


Participants44 patients with faecal incontinence were included.

All participants were women aged 18 years or over.


InterventionsA: Zinc-aluminium ointment
B: Placebo ointment

Duration of treatment: Applied on the anal canal mucosa 3 times daily over 4 weeks.


OutcomesWexner Faecal Incontinence Score reported before and after the treatment

A (n = 24): Before: 16.6 (6-20); After: 8.5 (0-11) P < 0.001

B (n = 20): Before: 16.7 (5-18); After: 13.1(5-17) P = 0.02

There was a significant difference in the final scores favouring the treatment group (P = 0.001)

For Quality of life "Fecal Incontinence Quality of Life (FIQL) score" was used which included the following parameters: lifestyle, conduct, embarrassment and depression.

Lifestyle:

A (n = 24): Baseline: 2.49(1.06); After: 3.58(1.18) P < 0.001

B (n = 20): Baseline: 2.50(1.01); After: 2.55(1.03) P = 0.151

Conduct:

A (n = 24): Baseline: 2.19(1.02); After: 3.12(1.16) P < 0.001

B (n = 20): Baseline: 2.17(0.91); After: 2.37(1.13) P = 0.104

Embarrassment:

A (n = 24): Baseline: 1.54(0.82); After: 2.5(1.32) P < 0.001

B (n = 20): Baseline: 1.56(0.74); After: 1.76(0.84) P = 0.043

Depression:

A (n = 24): Baseline: 2.51(1.01); After: 3.48(1.17) P = 0.001

B (n = 20): Baseline: 2.46(1.02); After: 2.71(1.13) P = 0.093

The quality of life score increased in both groups but more in the treatment group in all the parameters.

Adverse effects/ complications: A = 0/24; B = 0/20


NotesIt is mentioned that the inclusion criteria were faecal incontinence, minimal sphincter disruption on anal endosonography and it is also stated that "aluminium ointment is effective in the treatment of anal fissure" therefore it seems that all the patients had anal fissure although not specifically stated.


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Unclear riskReported as "randomized trial" however method of sequence generation not specified

Allocation concealment (selection bias)Unclear riskReported as "randomized trial" however method of allocation concealment not specified

Blinding of participants and personnel (performance bias)
All outcomes
Unclear riskReported as "double-blind" however it is not specifically mentioned who was blinded

Blinding of outcome assessment (detection bias)
All outcomes
Unclear riskReported as "double-blind" however it is not specifically mentioned who was blinded

Incomplete outcome data (attrition bias)
All outcomes
High riskEarlier it is mentioned that "six were lost to study" but later on it is reported that "one in the treatment group and four in the placebo group withdrew at the beginning of the study" i.e. five patients. They have not specified to which group the sixth patient belonged. Reasons for withdrawal also not reported.

Selective reporting (reporting bias)Unclear riskProtocol not available

Was use of a cross over design appropriate?Low riskThis is a randomised controlled trial and not a cross-over trial and this domain of risk of bias assessment is not applicable and would be judged as low risk.

Is it clear that the order of receiving treatment was randomised?Low riskThis is a randomised controlled trial and not a cross-over trial and this domain of risk of bias assessment is not applicable and would be judged as low risk.

Can it be assumed that the trial was not biased from carry over effects?Low riskThis is a randomised controlled trial and not a cross-over trial and this domain of risk of bias assessment is not applicable and would be judged as low risk.

Read 1982 #

MethodsCross-over randomised controlled trial


Participants26 patients (16 women) with chronic diarrhoea and FI
Heterogeneous group of patients with diarrhoea due to irritable bowel syndrome (n = 11), Crohn's disease (n = 2), ulcerative colitis (n = 1), diabetes mellitus (n = 2) and others including a group who were undiagnosed despite extensive tests
Mean age 45 years (range 24 to 82)
Exclusion criteria: none specified


InterventionsA: loperamide 4 mg three times a day
B: placebo
Length of treatment: two one-week treatment periods
Washout period: not specified
Dose titration: no


OutcomesEpisodes of FI per week (n, mean number, range): A: 26, 0.6 (0 to 6), B: 26, 0.9 (0 to 6), P < 0.01
Improvement (number having fewer incontinence episodes): A: 7/26, B: 2/26
Episodes of faecal urgency per week (n, mean number, range): A: 26, 1.52 (0 to 7), B: 26, 5.3 (0 to 27), P < 0.001
Improvement (number having fewer episodes of faecal urgency): A: 19/26, B: 3/26
Bowel movements per week (n, mean, range): A: 26, 11 (1 to 44), B: 26, 17 (0 to 54), P < 0.001
24-hour stool weight (n, mean g, range): A: 26, 102 (0 to 467), B: 26, 186 (0 to 466), P < 0.001
Per cent unformed stool per week (mean %, range): A: 40% (0 to 100), B: 57% (0 to 100), P < 0.001
Adverse effects (all mild): A: 18/26, B: 1/26 (constipation 11; abdominal pain 2; nausea and vomiting 3; exacerbation of diarrhoea 4)
Anal canal resting pressure (n, mean cm water, SD): A: 26, 84 (31), B: 26, 73 (31), P < 0.05
Anal canal maximum squeeze pressures: increased (but still below normal range) by loperamide only in the 17 participants who could not retain rectal saline. Within normal range in the 9 participants who could retain saline
Saline continence test (volume (mL water) at which first leak occurs, n, mean, SEM): A: 17, 950 (110), B: 17, 510 (100), P < 0.005
Recovery of rectoanal inhibitory reflex improved by loperamide (P < 0.05)
Rectal compliance enhanced by loperamide


NotesSome data only presented graphically, data calculated by approximate measurement
Data analysed using Wilcoxon's rank sum test for paired data, and Student's t test for paired data


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Unclear riskNot specified

Allocation concealment (selection bias)Unclear riskNot specified.

Blinding of participants and personnel (performance bias)
All outcomes
Low riskIt is stated that "Neither the patient, physician, or technician was aware of the preparation taken during the week. Finally, the technician who performed the objective tests was, in most instances, unaware of the subjective improvement of the patient during the previous week"

Blinding of outcome assessment (detection bias)
All outcomes
Low riskIt is stated that "Neither the patient, physician, or technician was aware of the preparation taken during the week. Finally, the technician who performed the objective tests was, in most instances, unaware of the subjective improvement of the patient during the previous week"

Incomplete outcome data (attrition bias)
All outcomes
Low riskNo incomplete data

Selective reporting (reporting bias)Unclear riskProtocol not available however, all the outcomes mentioned in the method section were reported

Was use of a cross over design appropriate?Low riskSeems appropriate

Is it clear that the order of receiving treatment was randomised?Unclear riskNot stated

Can it be assumed that the trial was not biased from carry over effects?High riskNo washout period

Ryan 1974

MethodsRandomised controlled trial


Participants87 patients admitted to a geriatric unit
Exclusion criteria: none specified


InterventionsA: Osmotic laxative (lactulose) 15 mL
B: 'no-treatment' control group
Length of treatment: 21 days


OutcomesNumber of days when help required from nurses (n/N total trial days): A: 283/801, B: 322/724, P < 0.05
Number of days when > 20 minutes help required: A: 20/801, B: 33/724
Total number of soiled items (n/N participants): A: 154/44, B: 332/43, P < 0.01
Number of days with soiled linen (n/N total trial days): A: 92/801, B: 164/724, P < 0.01
No side effects reported


NotesConcealment of allocation possibly inadequate
Characteristics of patients and comparability of intervention groups at baseline not reported


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Unclear riskMethod of sequence generation not specified

Allocation concealment (selection bias)Unclear riskNot specified

Blinding of participants and personnel (performance bias)
All outcomes
Unclear riskNot reported

Blinding of outcome assessment (detection bias)
All outcomes
Unclear riskNot reported

Incomplete outcome data (attrition bias)
All outcomes
High risk30 participants (14 in the treatment group and 16 in the 'no-treatment' group) were discharged early and did not complete the full trial period

Selective reporting (reporting bias)Unclear riskProtocol not available

Was use of a cross over design appropriate?Low riskThis is a randomised controlled trial and not a cross-over trial and this domain of risk of bias assessment is not applicable and would be judged as low risk.

Is it clear that the order of receiving treatment was randomised?Low riskThis is a randomised controlled trial and not a cross-over trial and this domain of risk of bias assessment is not applicable and would be judged as low risk.

Can it be assumed that the trial was not biased from carry over effects?Low riskThis is a randomised controlled trial and not a cross-over trial and this domain of risk of bias assessment is not applicable and would be judged as low risk.

Sun 1997 #

MethodsCross-over randomised controlled trial


Participants11 patients (8 women) with chronic diarrhoea and FI
Median age: 56 years (range 44 to 77)
Inclusion criteria: chronic diarrhoea; FI more than 1x/week; severe urgency at least 3x/week; negative screening for infection, faecal fat and occult blood; normal sigmoidoscopy
Exclusion criteria: large volume diarrhoea (> 500 mL/24 hours); passive FI (anal seepage)


InterventionsA: Loperamide oxide 4 mg twice daily
B: placebo
Length of treatment: two one-week treatment periods with one-week washout period before and after each arm
Dose titration: no


OutcomesNumber of people cured (no diarrhoea or incontinence in 24 hours): A: 7/11, B: 3/11, P < 0.05
Number of people improved (stool consistency better): A: 9/11, B: 3/11
Frequency of defecation (number of bowel movements per day) (n, mean, SD): A: 11, 1.43 (1), B: 11, 2 (1), P < 0.02
Proportion of days with formed stools (%, SD): A: 67% (39), B: 34% (31), P < 0.02
Stool weight, g (n, mean, SD): A: 11, 282 (212), B: 11, 423 (163), P = 0.11
Incontinence episodes
Visual analogue (scale-rated severity of FI) (n, mean, SD): A: 11, 26 (36), B: 11, 43 (37), P = 0.12
Adverse events: A: 6/11, B: 3/11 (constipation, abdominal pain, nausea and vomiting, headache)
Whole gut transit time (n, mean, SD): A: 11, 61 (13), B: 11, 39 (15), P < 0.001
Orocaecal gut transit time (n, mean, SD): A: 11, 296 (103), B: 11, 282 (121)
Anal canal resting pressure, mm Hg (n, mean, SD): A: 11, 76 (40), B: 11, 69 (35)
Anal canal maximum squeeze pressure, mm Hg (n, mean, SD): A: 11, 163 (86), B: 11, 155 (85)
Saline retention (continence) test, mL water (n, mean, SD): A: 11, 223 (274), B: 11, 150 (208)
Recto-anal inhibitory reflex.


NotesHeterogeneous disease groups (9 with irritable bowel syndrome, 1 with post-gastrectomy diarrhoea and one with post-cholecystectomy diarrhoea)
Normal range of mean wet stool weight = 57 to 100 g/day


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Unclear riskNot specified

Allocation concealment (selection bias)Unclear riskNot specified

Blinding of participants and personnel (performance bias)
All outcomes
Unclear riskReported as "double-blind study", however it is not specified who was blinded.

Blinding of outcome assessment (detection bias)
All outcomes
Unclear riskReported as "double-blind study", however it is not specified who was blinded.

Incomplete outcome data (attrition bias)
All outcomes
Low riskNo missing data

Selective reporting (reporting bias)High riskit is reported that "the 24-h faecal output (0800 h to 0800 h) was collected on days 4, 5, and 6 of each treatment week, and the net wet, consistency and dry weight were recorded", however the results are not reported for days 4 and 5 and only reported for day 6.

Was use of a cross over design appropriate?Low riskseems appropriate

Is it clear that the order of receiving treatment was randomised?Unclear riskNot reported

Can it be assumed that the trial was not biased from carry over effects?Low riskThere was a washout period of 1 week

 
Characteristics of excluded studies [ordered by study ID]

StudyReason for exclusion

Bliss 2001RCT but intervention does not include a drug.
Interventions: metamucil (psyllium), gum arabic, pectin.

Christensen 2006RCT but excluded as intervention does not include a drug.
Interventions: transanal irrigation, conservative lifestyle management including diet, fluid, physical activity, laxatives or constipating medicines if needed.

Drossman 2007Participants had diarrhoea and constipation, and not faecal incontinence.

Emblem 1989Not random allocation of patients to intervention groups.

Eogan 2007Participants were provided with lactulose to maintain soft stool and did not have faecal incontinence.

Freedman 1959Use of psychopharmacological agents (phenothiazine and amphetamine derivatives) for the treatment of incontinent schizophrenic patients.

Grijalva 2010Participants did not have faecal incontinence.

Harari 2004RCT but excluded as intervention does not include a drug.
Interventions: nurse management + lifestyles measures, routine care.

Henriksson 1992Participants had diarrhoea and not faecal incontinence.

Heymen 2004Reports results of an RCT comparing biofeedback and Kegel exercise training.

Heymen 2004aReports results of an RCT comparing biofeedback and Kegel exercise training.

Lauti 2008Participants in both the arms received loperamide and the trial compared low-residue diet with fibre supplement.

Qvitzau 1988Participants had diarrhoea and not faecal incontinence.

Rosman 2008Participants had bowel evacuation problem and not faecal incontinence

Santos 1961Not random allocation of patients to intervention groups.

Schneiter 1972Participants had post-operative constipation and not faecal incontinence.

Shoji 1993Participants were randomised into 2 groups (valproate and placebo). However, results for faecal incontinence are reported for the entire cohort.

Tu 2008Participants had diarrhoea and not faecal incontinence.

Van Assche 2012Participants had diarrhoea and not faecal incontinence.

Whitebird 2006Excluded as intervention does not include a drug ('The Fiber Study').
Interventions: gum arabic, psyllium, carboxymethyl cellulose, placebo.

 
Comparison 1. DRUG VERSUS PLACEBO

Outcome or subgroup titleNo. of studiesNo. of participantsStatistical methodEffect size

 1 Number of people failing to achieve full continenceOther dataNo numeric data

    1.1 Loperamide versus placebo
Other dataNo numeric data

    1.2 Diphenoxylate + atropine versus placebo
Other dataNo numeric data

    1.3 Phenylephrine gel versus placebo
Other dataNo numeric data

    1.4 Sodium valproate versus placebo
Other dataNo numeric data

 2 Number of people failing to improve incontinenceOther dataNo numeric data

    2.1 Loperamide versus placebo
Other dataNo numeric data

    2.2 Diphenoxylate + atropine versus placebo
Other dataNo numeric data

    2.3 Phenylephrine gel versus placebo
Other dataNo numeric data

 3 Number of faecal incontinence episodesOther dataNo numeric data

    3.1 Loperamide versus placebo
Other dataNo numeric data

    3.2 Phenylephrine cream versus placebo
Other dataNo numeric data

 4 Frequency of defecation (per day)Other dataNo numeric data

    4.1 Loperamide versus placebo
Other dataNo numeric data

    4.2 Diphenoxylate + atropine versus placebo
Other dataNo numeric data

    4.3 Sodium valproate versus placebo
Other dataNo numeric data

 5 Faecal incontinence scoreOther dataNo numeric data

    5.1 Loperamide versus placebo
Other dataNo numeric data

    5.2 Phenylephrine gel versus placebo
Other dataNo numeric data

    5.3 Zinc aluminium ointment versus placebo ointment
Other dataNo numeric data

 6 Stool weight (grammes in 24 hours)Other dataNo numeric data

    6.1 Loperamide versus placebo
Other dataNo numeric data

    6.2 Diphenoxylate + atropine versus placebo
Other dataNo numeric data

 7 Number of people using padsOther dataNo numeric data

    7.1 Loperamide versus placebo
Other dataNo numeric data

 8 Number of people with adverse effectsOther dataNo numeric data

    8.1 Loperamide versus placebo
Other dataNo numeric data

    8.2 Phenylephrine gel versus placebo
Other dataNo numeric data

    8.3 Sodium valproate versus placebo
Other dataNo numeric data

    8.4 Zinc aluminium ointment versus placebo ointment
Other dataNo numeric data

 9 Number of people with perianal skin problemsOther dataNo numeric data

    9.1 Sodium valproate versus placebo
Other dataNo numeric data

 10 Maximum resting anal pressure (mmHg)Other dataNo numeric data

    10.1 Loperamide versus placebo
Other dataNo numeric data

    10.2 Diphenoxylate + atropine versus placebo
Other dataNo numeric data

    10.3 Phenylephrine gel versus placebo
Other dataNo numeric data

    10.4 Sodium valproate versus placebo
Other dataNo numeric data

 11 ManometryOther dataNo numeric data

    11.1 Phenylephrine gel versus placebo
Other dataNo numeric data

 12 Maximum anal squeeze pressure (mmHg)Other dataNo numeric data

    12.1 Loperamide versus placebo
Other dataNo numeric data

    12.2 Diphenoxylate + atropine versus placebo
Other dataNo numeric data

 13 Duration of squeeze (seconds)Other dataNo numeric data

    13.1 Diphenoxylate + atropine versus placebo
Other dataNo numeric data

 14 Sensory threshold (cm water)Other dataNo numeric data

    14.1 Loperamide versus placebo
Other dataNo numeric data

    14.2 Diphenoxylate + atropine versus placebo
Other dataNo numeric data

 15 Saline retention test (mL)Other dataNo numeric data

    15.1 Loperamide versus placebo
Other dataNo numeric data

    15.2 Diphenoxylate + atropine versus placebo
Other dataNo numeric data

 16 Whole-gut transit timeOther dataNo numeric data

    16.1 Loperamide versus placebo
Other dataNo numeric data

 17 Number of soiled items (bedding and or clothing)Other dataNo numeric data

 18 Help required from nursesOther dataNo numeric data

    18.1 Laxative (lactulose) versus placebo
Other dataNo numeric data

 19 Faecal Incontinence Quality of Life (FIQL) scoreOther dataNo numeric data

    19.1 Zinc aluminium ointment versus placebo ointment
Other dataNo numeric data

    19.2 Phenylephrine gel versus placebo
Other dataNo numeric data

 
Analysis 1.1 Comparison 1 DRUG VERSUS PLACEBO, Outcome 1 Number of people failing to achieve full continence.
Number of people failing to achieve full continence

StudyDrugPlaceboSignificance

Loperamide versus placebo

Hallgren 1994 #3/28 during the day
1/28 during the night
7/28 during the day
11/28 during the night

Sun 1997 #4/11 in 24 hours
(loperamide oxide)
8/11 in 24 hoursP < 0.05

Diphenoxylate + atropine versus placebo

Harford 1980 #0/15 in 24 hours3/15 in 24 hours

Phenylephrine gel versus placebo

Carapeti 2000b #8/1212/12

Sodium valproate versus placebo

Kusunoki 1990 #3/1710/17

 
Analysis 1.2 Comparison 1 DRUG VERSUS PLACEBO, Outcome 2 Number of people failing to improve incontinence.
Number of people failing to improve incontinence

StudyDrugPlacebo

Loperamide versus placebo

Read 1982 #Episodes of urgency: 7/26
Incontinence episodes: 19/26

Per cent unformed stool per week (mean, range): 40% (0%-100%)
Episodes of urgency: 23/26
Incontinence episodes: 24/26

Per cent unformed stool per week (mean, range): 57% (0%-100%) (P < 0.001)

Sun 1997 #No improvement in stool consistency: 2/11

Per cent of days with unformed stools: 33%

(loperamide oxide)
No improvement in stool consistency: 8/11

Per cent of days with unformed stools: 66% (P < 0.02)

Diphenoxylate + atropine versus placebo

Harford 1980 #No improvement in stool weight and frequency: 3/15No improvement in stool weight and frequency: 3/15

Phenylephrine gel versus placebo

Carapeti 2000a #No subjective improvement: 30/3634/36

Carapeti 2000b #No undefined 'improvement': 6/1211/12

 
Analysis 1.3 Comparison 1 DRUG VERSUS PLACEBO, Outcome 3 Number of faecal incontinence episodes.
Number of faecal incontinence episodes

StudyDrugPlacebo

Loperamide versus placebo

Read 1982 #Mean 0.6
(range 0-6)
per week
Mean 0.9 (range 0-6)

Phenylephrine cream versus placebo

Lumi 2009Median 5.4

(range 0-14)
Median 9

(range 0-19)

 
Analysis 1.4 Comparison 1 DRUG VERSUS PLACEBO, Outcome 4 Frequency of defecation (per day).
Frequency of defecation (per day)

StudyDrugPlaceboSignificance

Loperamide versus placebo

Hallgren 1994 #N 28 mean 4.24 (SD 1.86)N 28 mean 6.43 (SD 1.99)

Read 1982 #N 26 mean 1.6 (range 1-6.3)N 26 mean 2.4 (range 0-7.7)P < 0.001 Wilcoxon's rank sum test for paired data

Sun 1997 #N 11 mean 1.43 (SD 1)
(loperamide oxide)
N 11 mean 2 (SD 1)P < 0.02

Diphenoxylate + atropine versus placebo

Harford 1980 #N 15 mean 2.6 (SD 2.71)N 15 mean 4.9 (SD 3.1)

Sodium valproate versus placebo

Kusunoki 1990 #N 17 mean 5.98 (SD 2.97)N 17 mean 9.65 (SD 3.59)

 
Analysis 1.5 Comparison 1 DRUG VERSUS PLACEBO, Outcome 5 Faecal incontinence score.
Faecal incontinence score

StudyDrugPlaceboSignificance

Loperamide versus placebo

Sun 1997 #visual analogue incontinence
scale:
N 11 mean 26 (SD 36)
loperamide oxide
N 11 mean 43 (SD 37)P = 0.12

Phenylephrine gel versus placebo

Carapeti 2000a #N 18 mean 12.5 (SD 3.4)N 18 mean 12.6 (SD 4.2)No significant difference

Carapeti 2000b #N 12 mean 12.2 (SD 5.7)N 12 mean 16.5 (SD 4.4)

Park 2007Anal incontinence evaluated with Faecal Incontinence Severity Index (FISI) and reported as mean (SD)

n = 17; Baseline: 32.5 (14.5); After: 32.3 (14.7) P = 0.940
Anal incontinence evaluated with Faecal Incontinence Severity Index (FISI) and reported as mean (SD)

n = 12; Baseline: 32.1 (11.2); After: 32.4 (14.4) P = 0.626

Zinc aluminium ointment versus placebo ointment

Pinedo 2012Wexner Faecal Incontinence Score reported before and after the treatment and reported as mean (SD)

n = 24; Before: 16.6 (6-20); After: 8.5 (0-11) P = < 0.001
Wexner Faecal Incontinence Score reported before and after the treatmentand reported as mean (SD)

n = 20; Before: 16.7 (5-18); After: 13.1 (5-17) P = 0.02
There was a significant difference in the final scores favouring the treatment group (P = 0.001)

 
Analysis 1.6 Comparison 1 DRUG VERSUS PLACEBO, Outcome 6 Stool weight (grammes in 24 hours).
Stool weight (grammes in 24 hours)

StudyDrugPlaceboSignificance

Loperamide versus placebo

Read 1982 #N 26 mean 102 (range 0-467)N 26 mean 186 (range 0-466)P < 0.001 Wilcoxon's rank sum test for paired data

Sun 1997 #N 11 mean 282 (SD 212)
(loperamide oxide)
N 11 mean 423 (SD 163)P = 0.11

Diphenoxylate + atropine versus placebo

Harford 1980 #N 15 mean 256 (SD 333)N 15 mean 460 (SD 581)

 
Analysis 1.7 Comparison 1 DRUG VERSUS PLACEBO, Outcome 7 Number of people using pads.
Number of people using pads

StudyDrugPlacebo

Loperamide versus placebo

Hallgren 1994 #During the day: 1/28
During the night:
1/28
During the day:
3/28
During the night: 6/28

 
Analysis 1.8 Comparison 1 DRUG VERSUS PLACEBO, Outcome 8 Number of people with adverse effects.
Number of people with adverse effects

StudyDrugPlacebo

Loperamide versus placebo

Read 1982 #18/26 (constipation 11, diarrhoea 4, nausea and vomiting 3, abdominal pain 2)1/26 (abdominal pain)

Sun 1997 #6/11 (headache, nausea, dizzyness, abdominal pain, constipation)
(loperamide oxide)
3/11

Phenylephrine gel versus placebo

Carapeti 2000a #3/36 (mild dermatitis after phenylephrine gel application, which settled when drug stopped)0/36

Carapeti 2000b #0/120/12

Cheetham 2001 #2/10 (burning sensation after phenylephrine gel application, which settled within minutes)0/10

Park 2007Dermatitis reaction: 5/17; B = 1/12
Palpitation: 0/17; B = 1/12
Headache: 2/17; B = 0/12
Dermatitis reaction: 1/12
Palpitation: 1/12
Headache: 0/12

Sodium valproate versus placebo

Kusunoki 1990 #8/17 (abdominal pain and nausea)0/17

Zinc aluminium ointment versus placebo ointment

Pinedo 20120/240/20

 
Analysis 1.9 Comparison 1 DRUG VERSUS PLACEBO, Outcome 9 Number of people with perianal skin problems.
Number of people with perianal skin problems

StudyDrugPlacebo

Sodium valproate versus placebo

Kusunoki 1990 #3/179/17

 
Analysis 1.10 Comparison 1 DRUG VERSUS PLACEBO, Outcome 10 Maximum resting anal pressure (mmHg).
Maximum resting anal pressure (mmHg)

StudyDrugPlacebo

Loperamide versus placebo

Hallgren 1994 #N 28 mean 62 (SD 16)versus
N 28 mean 55 (SD 9)

Sun 1997 #N 11 mean 76 (SD 40)
(loperamide oxide )
N 11 mean 69 (SD 35)

Diphenoxylate + atropine versus placebo

Harford 1980 #N 15 mean 41 (SD 23)N 15 mean 39 (SD 19)

Phenylephrine gel versus placebo

Carapeti 2000a #N 18 mean 65 (SD 21)N 18 mean 54 (SD 21)

Carapeti 2000b #N 12 mean 89 (SD 17)N 12 mean 75 (SD 14)

Cheetham 2001 #Statistically significant differences between phenylephrine gel (in concentrations of 30% and 40% only)compared with placebo (P < 0.05)

Sodium valproate versus placebo

Kusunoki 1990 #N 17 mean 63.6 (SD 12.4)N 17 mean 42.5 (SD 8.9)

 
Analysis 1.11 Comparison 1 DRUG VERSUS PLACEBO, Outcome 11 Manometry.
Manometry

StudyDomainDrug (n = 17); reported as mean (SD)Placebo (n = 12); reported as mean (SD)

Phenylephrine gel versus placebo

Park 2007Resting pressure (mmHg)Baseline: 30.0 (12.3); After: 27.3 (12.7) P = 0.362Baseline: 32.6 (14.2); After: 27.2 (15.0) P = 0.306

Park 2007Squeezing pressure (mmHg)Baseline: 143.3 (60.5); After: 160.4 (76.9) P = 0.083Baseline: 152.6 (86.5); After: 147.1 (76.5) P = 0.625

Park 2007Sustained duration (s)Baseline: 41.9 (24.5); After: 44.9 (48.3) P = 0.848Baseline: 39.6 (24.4); After: 32.8 (14.4) P = 0.187

Park 2007Sphincter length (cm)Baseline: 3.2 (0.9); After: 3.4 (0.8) P = 0.368Baseline: 3.5 (0.8); After: 3.4 (0.8) P = 0.743

Park 2007High pressure zone (cm)Baseline: 2.4 (2.1); After: 1.9 (0.5) P = 0.378Baseline: 2.1 (0.9); After: 2.3 (0.9) P = 0.556

 
Analysis 1.12 Comparison 1 DRUG VERSUS PLACEBO, Outcome 12 Maximum anal squeeze pressure (mmHg).
Maximum anal squeeze pressure (mmHg)

StudyDrugPlacebo

Loperamide versus placebo

Hallgren 1994 #N 28 mean 223 (SD 82)N 28 mean 219 (SD 93)

Sun 1997 #N 11 mean 163 (SD 86)
(loperamide oxide)
N 11 mean 155 (SD 85)

Diphenoxylate + atropine versus placebo

Harford 1980 #N 15 mean 94 (SD 68)N 15 mean 96 (SD 68)

 
Analysis 1.13 Comparison 1 DRUG VERSUS PLACEBO, Outcome 13 Duration of squeeze (seconds).
Duration of squeeze (seconds)

StudyDrugPlacebo

Diphenoxylate + atropine versus placebo

Harford 1980 #N 15 mean 87 (SD 127)N 15 mean 86 (SD 127)

 
Analysis 1.14 Comparison 1 DRUG VERSUS PLACEBO, Outcome 14 Sensory threshold (cm water).
Sensory threshold (cm water)

StudyDrugPlacebo

Loperamide versus placebo

Hallgren 1994 #N 28 mean 29.6 (SD 11.7)N 28 mean 26.5 (SD 14.9)

Diphenoxylate + atropine versus placebo

Harford 1980 #N 15 mean 12 (SD 12)N 15 mean 31 (SD 62)

 
Analysis 1.15 Comparison 1 DRUG VERSUS PLACEBO, Outcome 15 Saline retention test (mL).
Saline retention test (mL)

StudyDrugPlaceboSignificance

Loperamide versus placebo

Sun 1997 #N 11 mean 223 (SD 274)
(loperamide oxide)
versus
N 11 mean 150 (SD 208 )
P = 0.07

Diphenoxylate + atropine versus placebo

Harford 1980 #N 15 mean 492 (SD 461)N 15 mean 486 (SD 364)

 
Analysis 1.16 Comparison 1 DRUG VERSUS PLACEBO, Outcome 16 Whole-gut transit time.
Whole-gut transit time

StudyDrugPlaceboSignificance

Loperamide versus placebo

Sun 1997 #N 11 mean 61 hours (SD 13)
(loperamide oxide)
N 11 mean 39 hours (SD 15)Significantly prolonged (P < 0.001) in patients taking loperamide oxide

 
Analysis 1.17 Comparison 1 DRUG VERSUS PLACEBO, Outcome 17 Number of soiled items (bedding and or clothing).
Number of soiled items (bedding and or clothing)

StudyDrugPlaceboSignificance

Ryan 1974154 items during trial period332 itemsP < 0.01

 
Analysis 1.18 Comparison 1 DRUG VERSUS PLACEBO, Outcome 18 Help required from nurses.
Help required from nurses

StudyDrugPlaceboSignificance

Laxative (lactulose) versus placebo

Ryan 1974283 days of help322 days of helpP < 0.05 during trial period

 
Analysis 1.19 Comparison 1 DRUG VERSUS PLACEBO, Outcome 19 Faecal Incontinence Quality of Life (FIQL) score.
Faecal Incontinence Quality of Life (FIQL) score

StudyDomainsDrug (n = 17); reported as mean (SD)Placebo (n = 12); reported as mean (SD)

Zinc aluminium ointment versus placebo ointment

Pinedo 2012LifestyleBaseline: 2.49 (1.06); After: 3.58 (1.18) P = < 0.001Baseline: 2.50 (1.01); After: 2.55 (1.03) P = 0.151

Pinedo 2012ConductBaseline: 2.19 (1.02); After: 3.12 (1.16) P = < 0.001Baseline: 2.17 (0.91); After: 2.37 (1.13) P = 0.104

Pinedo 2012EmbarrassmentBaseline: 1.54 (0.82); After: 2.5 (1.32) P = < 0.001Baseline: 1.56 (0.74); After: 1.76 (0.84) P = 0.043

Pinedo 2012DepressionBaseline: 2.51 (1.01); After: 3.48 (1.17) P = 0.001Baseline: 2.46 (1.02); After: 2.71 (1.13) P = 0.093

Phenylephrine gel versus placebo

Park 2007LifestyleBaseline: 2.9 (0.8); After: 2.9 (1.0) P = 0.801Baseline: 2.7 (0.5); After: 3.0 (0.8) P = 0.269

Park 2007CopingBaseline: 2.5 (0.9); After: 2.8 (0.9) P= 0.110Baseline: 2.5 (0.5); After: 2.8 (0.5) P = 0.119

Park 2007DepressionBaseline: 3.2 (0.7); After: 3.2 (0.8) P = 0.415Baseline: 3.1 (0.5); After: 3.2 (0.5) P = 0.554

Park 2007EmbarrassmentBaseline: 2.7 (0.7); After: 3.0 (0.7) P = 0.090Baseline: 2.7 (0.6); After: 2.6 (0.8) P = 0.855

 
Comparison 2. ONE DRUG VERSUS ANOTHER DRUG OR A COMBINATIONOF DRUGS

Outcome or subgroup titleNo. of studiesNo. of participantsStatistical methodEffect size

 1 Loperamide versus codeine versus diphenoxylate + atropine sulfateOther dataNo numeric data

    1.1 Solid stool (%)
Other dataNo numeric data

    1.2 Number of people with faecal incontinence
Other dataNo numeric data

    1.3 Stool frequency
Other dataNo numeric data

    1.4 Number of people with urgency
Other dataNo numeric data

    1.5 Adverse effects
Other dataNo numeric data

    1.6 Adverse effects causing withdrawal
Other dataNo numeric data

 2 Osmotic laxative (lactulose) versus osmotic laxative + glycerine suppository + enemaOther dataNo numeric data

    2.1 Number of faecal incontinence episodes in 4 weeks
Other dataNo numeric data

    2.2 Number of soiled items (bedding and or clothing) in 4 weeks
Other dataNo numeric data

 3 Oral versus suppository administration of loperamideOther dataNo numeric data

 4 Different doses of oral loperamideOther dataNo numeric data

    4.1 Stool frequency
Other dataNo numeric data

    4.2 Stool consistency
Other dataNo numeric data

    4.3 Faecal incontinence
Other dataNo numeric data

    4.4 Dose response for faecal incontinence
Other dataNo numeric data

    4.5 Adverse effects
Other dataNo numeric data

 
Analysis 2.1 Comparison 2 ONE DRUG VERSUS ANOTHER DRUG OR A COMBINATIONOF DRUGS, Outcome 1 Loperamide versus codeine versus diphenoxylate + atropine sulfate.
Loperamide versus codeine versus diphenoxylate + atropine sulfate

StudyLoperamideCodeineDiphenox. + atropineSignificance

Solid stool (%)

Palmer 1980 #67.8% (SD 34)58.4% (SD 25.9)36.3% (SD 33.3)Diphenoxylate was associated with a signficantly smaller percentage of solid stools than either loperamide or codeine (P < 0.01)

Number of people with faecal incontinence

Palmer 1980 #2/253/256/25

Stool frequency

Palmer 1980 #N 15 mean 1.8 (SD 0.3)N 15 mean 1.9 (SD 0.3)N 15 mean 1.9 (SD 0.3)

Number of people with urgency

Palmer 1980 #3/164/179/17Diphenoxylate was significantly worse than loperamide or codenine, P < 0.05
(completed treatment periods only)

Adverse effects

Palmer 1980 #22 in 10/25 patients29 in 12/25 patients39 in 12/25 patientsSignificantly more adverse effects with diphenoxylate than loperamide, P < 0.05

Adverse effects causing withdrawal

Palmer 1980 #4/254/255/25

 
Analysis 2.2 Comparison 2 ONE DRUG VERSUS ANOTHER DRUG OR A COMBINATIONOF DRUGS, Outcome 2 Osmotic laxative (lactulose) versus osmotic laxative + glycerine suppository + enema.
Osmotic laxative (lactulose) versus osmotic laxative + glycerine suppository + enema

StudyLactuloseLactul + supp + enemaSignificance

Number of faecal incontinence episodes in 4 weeks

Chassagne 2000N 61 mean 24 (SD 11.5 )N 62 mean 24 (SD 10.8)P = 0.9

Number of soiled items (bedding and or clothing) in 4 weeks

Chassagne 2000N 61 mean 80 (SD 16.1)N 62 mean 78 (SD 20.7)P = 0.55

 
Analysis 2.3 Comparison 2 ONE DRUG VERSUS ANOTHER DRUG OR A COMBINATIONOF DRUGS, Outcome 3 Oral versus suppository administration of loperamide.
Oral versus suppository administration of loperamide

StudyDataSignificance

Cohen 2001 #Oral administration resulted in decreased stool frequency compared with suppository administrationP < 0.02

 
Analysis 2.4 Comparison 2 ONE DRUG VERSUS ANOTHER DRUG OR A COMBINATIONOF DRUGS, Outcome 4 Different doses of oral loperamide.
Different doses of oral loperamide

StudyOutcome informationSignificance

Stool frequency

Fox 2005 #No effect

Stool consistency

Fox 2005 #Trend for increased stool consistency from median (IQR) score 0.7 (0.5 to 0.9) with placebo to 0.4 (0.3 to 0.6) with 6 mg dose (0 = all hard, 1 = all liquid)

Faecal incontinence

Fox 2005 #Less faecal spotting and incontinence with loperamide vs placeboP < 0.05

Dose response for faecal incontinence

Fox 2005 #Significant positive dose-response relationship with increasing dose of loperamide (reduced FI with 2 mg dose, and almost no FI with 4 mg and 6 mg doses)

Adverse effects

Fox 2005 #Adverse effects: none (specifically no severe constipation with the highest doses)