title: Pharmacological interventions for recurrent abdominal pain in childhood.
abstract: BACKGROUND
  Between 4% and 25% of school-aged children at some stage complain of recurrent abdominal pain (RAP) of sufficient severity to interfere with their daily lives. When no clear organic cause is found, the children are managed with reassurance and simple measures; a large range of pharmacological interventions have been recommended for use in these children.
  
  
  OBJECTIVE
  To determine the effectiveness of pharmacological interventions for RAP in children of school age.
  
  
  METHODS
  We searched the Cochrane Central Register of Controlled Trials (CENTRAL), Ovid MEDLINE, Embase, and eight other electronic databases up to June 2016. We also searched two trials registers and contacted researchers of published studies.
  
  
  METHODS
  Randomised controlled trials involving children aged five to 18 years old with RAP or an abdominal pain-related functional gastrointestinal disorder, as defined by the Rome III criteria (Rasquin 2006). The interventions were any pharmacological intervention compared to placebo, no treatment, waiting list, or standard care. The primary outcome measures were pain intensity, pain duration or pain frequency, and improvement in pain. The secondary outcome measures were school performance, social or psychological functioning, and quality of daily life.
  
  
  METHODS
  Two review authors independently screened titles, abstracts, and potentially relevant full-text reports for eligible studies. Two review authors extracted data and performed a 'Risk of bias' assessment. We used the GRADE approach to rate the overall quality of the evidence. We deemed a meta-analysis to be not appropriate as the studies were significantly heterogeneous. We have consequently provided a narrative summary of the results.
  
  
  RESULTS
  This review included 16 studies with a total of 1024 participants aged between five and 18 years, all of whom were recruited from paediatric outpatient clinics. Studies were conducted in seven countries: seven in the USA, four in Iran, and one each in the UK, Switzerland, Turkey, Sri Lanka, and India. Follow-up ranged from two weeks to four months. The studies examined the following interventions to treat RAP: tricyclic antidepressants, antibiotics, 5-HT4 receptor agonists, antispasmodics, antihistamines, H2 receptor antagonists, serotonin antagonists, selective serotonin re-uptake inhibitors, a dopamine receptor antagonist, and a hormone. Although some single studies reported that treatments were effective, all of these studies were either small or had key methodological weaknesses with a substantial risk of bias. None of these 'positive' results have been reproduced in subsequent studies. We judged the evidence of effectiveness to be of low quality. No adverse effects were reported in these studies.
  
  
  CONCLUSIONS
  There is currently no convincing evidence to support the use of drugs to treat RAP in children. Well-conducted clinical trials are needed to evaluate any possible benefits and risks of pharmacological interventions. In practice, if a clinician chooses to use a drug as a 'therapeutic trial', they and the patient need to be aware that RAP is a fluctuating condition and any 'response' may reflect the natural history of the condition or a placebo effect, rather than drug efficacy.
authors.affiliation: Paediatrics, Royal Devon and Exeter Hospital, Barrack Road, Exeter, England, UK, EX2 5DW.
authors.forename: Alice E
authors.initials: AE
authors.lastname: Martin
authors.affiliation: NIHR CLAHRC South West Peninsula (PenCLAHRC), University of Exeter Medical School, St Luke's Campus, Exeter, England, UK, EX1 2LU.
authors.forename: Tamsin V
authors.initials: TV
authors.lastname: Newlove-Delgado
authors.affiliation: NIHR CLAHRC South West Peninsula (PenCLAHRC), University of Exeter Medical School, St Luke's Campus, Exeter, England, UK, EX1 2LU.
authors.forename: Rebecca A
authors.initials: RA
authors.lastname: Abbott
authors.affiliation: NIHR CLAHRC South West Peninsula (PenCLAHRC), University of Exeter Medical School, St Luke's Campus, Exeter, England, UK, EX1 2LU.
authors.forename: Alison
authors.initials: A
authors.lastname: Bethel
authors.affiliation: NIHR CLAHRC South West Peninsula (PenCLAHRC), University of Exeter Medical School, St Luke's Campus, Exeter, England, UK, EX1 2LU.
authors.forename: Joanna
authors.initials: J
authors.lastname: Thompson-Coon
authors.affiliation: NIHR CLAHRC South West Peninsula (PenCLAHRC), University of Exeter Medical School, St Luke's Campus, Exeter, England, UK, EX1 2LU.
authors.forename: Rebecca
authors.initials: R
authors.lastname: Whear
authors.affiliation: NIHR CLAHRC South West Peninsula (PenCLAHRC), University of Exeter Medical School, St Luke's Campus, Exeter, England, UK, EX1 2LU.
authors.forename: Stuart
authors.initials: S
authors.lastname: Logan
mesh_terms: D015746:Abdominal Pain / Q000188:drug therapy*; D000293:Adolescent; D002648:Child; D002675:Child, Preschool; D006801:Humans; D016032:Randomized Controlled Trials as Topic; D012008:Recurrence; D016896:Treatment Outcome