What is the aim of this review?
The aim of this Cochrane Review was to find out whether antidepressants can improve symptoms in children and adolescents with functional abdominal pain disorders (FAPDs). We collected and analysed data from three studies with a total of 223 children and adolescents to answer this question.
The question of whether antidepressants can improve symptoms in children and adolescents with FAPDs remains unanswered. There were no serious adverse events when compared with placebo (dummy treatment). The number of studies was low, and the number of people in them was also low, meaning that more studies are needed to answer the question.
What was studied in the review?
FAPDs are common in childhood and adolescence. In most cases, no medical reason for the pain can be found. There are various drug treatment approaches for the different types of FAPDs. Antidepressants have been shown to be effective in some studies of adults with FAPDs. Consequently, children and adolescents with similar complaints are sometimes treated with antidepressants.
What are the main results of the review?
We searched for randomised controlled trials (RCTs; clinical studies where people are randomly put into one of two or more treatment groups) comparing antidepressants with placebo (dummy treatment).
We found three studies eligible for inclusion: two using amitriptyline (AMI) and one using citalopram, involving a total of 223 young people.
1. It is uncertain whether there is a difference in the number of people who had successful treatment when on antidepressants compared with placebo.
2. It is uncertain whether there is a difference in the number of people who withdraw from treatment due to adverse events when on antidepressants compared with placebo.
We are uncertain whether antidepressants can improve symptoms in children and adolescents with FAPDs. This is because the studies had very few participants and were not conducted using reliable methods. With the evidence presented in these studies, we are unable to draw strong conclusions about the effectiveness of antidepressants for this problem; better-designed studies with more participants are needed.
How up-to-date is this review?
This review is up-to-date as of February 2020.
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.
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.
To evaluate the current evidence for the efficacy and safety of antidepressants for FAPDs in children and adolescents.
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.
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.
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.
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.