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Meta-Analysis
. 2021 Feb 9;2(2):CD008013.
doi: 10.1002/14651858.CD008013.pub3.

Antidepressants for functional abdominal pain disorders in children and adolescents

Clara Marieke Andrea de Bruijn #  1 , Robyn Rexwinkel #  1 , Morris Gordon  2 , Marc Benninga  3 , Merit M Tabbers  4
Affiliations
Meta-Analysis

Antidepressants for functional abdominal pain disorders in children and adolescents

Clara Marieke Andrea de Bruijn et al. Cochrane Database Syst Rev. .

Abstract

Background: Functional Abdominal Pain Disorders (FAPDs) present a considerable burden to paediatric patients, impacting quality of life, school attendance and causing higher rates of anxiety and depression disorders. There are no international guidelines for the management of this condition. A previous Cochrane Review in 2011 found no evidence to support the use of antidepressants in this context.

Objectives: To evaluate the current evidence for the efficacy and safety of antidepressants for FAPDs in children and adolescents.

Search methods: In this updated review, we searched the Cochrane Library, PubMed, MEDLINE, Embase, PsycINFO and two clinical trial registers from inception until 03 February 2020. We also updated our search of databases of ongoing research, reference lists and 'grey literature' from inception to 03 February 2020.

Selection criteria: We included randomised controlled trials (RCTs) comparing antidepressants to placebo, to no treatment or to any other intervention, in children aged 4 to 18 years with a FAPD diagnosis as per the Rome or any other defined criteria (as defined by the authors). The primary outcomes of interest included treatment success (as defined by the authors), pain severity, pain frequency and withdrawal due to adverse events.

Data collection and analysis: Two review authors checked all citations independently, resolving disagreement with a third-party arbiter. We reviewed all potential studies in full text, and once again made independent decisions, with disagreements resolved by consensus. We conducted data extraction and 'Risk of bias' assessments independently, following Cochrane methods. Where homogeneous data were available, we performed meta-analysis using a random-effects model. We conducted GRADE analysis.

Main results: We found one new study in this updated search, making a total of three trials (223 participants) eligible for inclusion: two using amitriptyline (AMI) and one using citalopram. For the primary outcome of treatment success, two studies used reports of success on a symptom-based Likert scale, with either a two-point reduction or the two lowest levels defined as success. The third study defined success as a 15% improvement in quality of life (QOL) ratings scales. Therefore, meta-analysis did not include this final study due to the heterogeneity of the outcome measure. There is low-certainty evidence that there may be no difference when antidepressants are compared with placebo (risk ratio (RR) 1.17, 95% confidence interval (CI) 0.87 to 1.56; 2 studies, 205 participants; I2 = 0%). We downgraded the evidence for significant imprecision due to extremely sparse data (see Summary of findings table 1). The third study reported that participants receiving antidepressants were significantly more likely than those receiving placebo to experience at least a 15% improvement in overall QOL score at 10 and 13 weeks (P = 0.007 and P = 0.002, respectively (absolute figures were not given)). The analysis found no difference in withdrawals due to adverse events between antidepressants and placebo: RR 3.17 (95% CI 0.65 to 15.33), with very low certainty due to high risk of bias in studies and imprecision due to low event and participant numbers. Sensitivity analysis using a fixed-effect model and analysing just for AMI found no change in this result. Due to heterogeneous and limited reporting, no further meta-analysis was possible.

Authors' conclusions: There may be no difference between antidepressants and placebo for treatment success of FAPDs in childhood. There may be no difference in withdrawals due to adverse events, but this is also of low certainty. There is currently no evidence to support clinical decision making regarding the use of these medications. Further studies must consider sample size, homogenous and relevant outcome measures and longer follow up.

PubMed Disclaimer

Conflict of interest statement

MB: Consultant for Shire, Norgine, Coloplast, Danone, Takeda, Allergan, Shire, FrieslandCampina, United Pharamceuticals.

MT: None known

MG: Since August 2016, I have received travel fees to attend international scientific and training meetings from Pharma companies. These grants included no honoraria, inducement, advisory role or any other relationship and were restricted to the travel and meeting related costs of attending such meetings. These include: DDW May 2017, World Congress of Gastroenterology October 2017, DDW May 2018, Advances in IBD December 2018, DDW May 2019. None of these companies have had any involvement in any works completed by me and I have never had any payments for any other activities for them, as confirmed below. From this date onwards, I have made a personal undertaking to take no further funds from any pharmaceutical or formula company in any form for travel or other related activities. This is to lift the limitations such funding has on my ability to act as a first and corresponding author on reviews, in line with the Cochrane policies on such matters and is reported in line with these policies. These current declarations will expire over the next three years and this statement updated regularly to reflect this. RR: None known.

CB: None known.

Figures

1
1
Study flow diagram.
2
2
Methodological quality summary: review authors' judgements about each methodological quality item for each included study.
3
3
Risk of bias graph: review authors' judgements about each risk of bias item presented as percentages across all included studies.
1.1
1.1. Analysis
Comparison 1: antidepressant versus placebo, Outcome 1: Global improvement
1.2
1.2. Analysis
Comparison 1: antidepressant versus placebo, Outcome 2: Withdrawals due to adverse events
See this image and copyright information in PMC

Update of

References

References to studies included in this review

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References to ongoing studies

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