TY - JOUR
T1 - Antidepressants for functional abdominal pain disorders in children and adolescents
AU - de Bruijn, Clara Marieke Andrea
AU - Rexwinkel, Robyn
AU - Gordon, Morris
AU - Benninga, Marc
AU - Tabbers, Merit M.
N1 - Funding Information: We acknowledge the great work and contributions by Angela Kaminski, Adrian Kamper, Kylie Thaler, Andrea Chapman and Gerald Gartlehner to the original Cochrane Review published in 2012 (Kaminski 2012). The updated search strategies in December 2019 were developed and run by Yuhong Yuan (Information Specialist, Cochrane Gut Group). We are grateful to the authors who kindly responded to our request for clarification of the protocol and additional data on the trials in which they were involved. Finally, the review authors would also like to thank the following editors and peer referees who provided comments to improve the review: Dr. Paul Moayyedi (Editor), Dr. Maciej Ko?odziej (referee), Dr. Taher Kagalwala (referee) and an anonymous referee, and Kate Cahill for copy-editing the review. Publisher Copyright: Copyright © 2021 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd. Copyright: Copyright 2021 Elsevier B.V., All rights reserved.
PY - 2021/2/9
Y1 - 2021/2/9
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85101368703&partnerID=8YFLogxK
U2 - https://doi.org/10.1002/14651858.CD008013.pub3
DO - https://doi.org/10.1002/14651858.CD008013.pub3
M3 - Review article
C2 - 33560523
SN - 1469-493X
VL - 2021
SP - CD008013
JO - Cochrane database of systematic reviews (Online)
JF - Cochrane database of systematic reviews (Online)
IS - 2
M1 - CD008013
ER -