Antidepressants for the treatment of children and adolescents with functional abdominal pain disorders

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.

Key messages

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.

Conclusion

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.

Authors' conclusions: 

There is insufficient evidence to determine the effect of antidepressants on treatment success of FAPDs in childhood when compared with placebo (low certainty evidence). The small number of participants in the studies and low number of withdrawals did not enable us to determine reliably whether children are likely to stop taking medication due to adverse events (low certainty evidence). There is currently very little 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.

Read the full 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 strategy: 

In this updated review, we searched The Cochrane Library, PubMed, MEDLINE, EMBASE, PsycINFO and two clinical trial registers from inception until February 3th, 2020. We also updated our search of databases of ongoing research, reference lists and 'grey literature' from inception to February 3th, 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: 

All citations were reviewed independently by two authors, with disagreement solved with a third-party arbiter. All potential studies had full texts reviewed, and once again, independent decisions made, with disagreement solved by consensus. Data extraction and risk of bias assessment was completed independently following Cochrane standards. Where homogenous data was available, meta-analysis was performed using a random effects model. GRADE assessement of the certainty of the evidence was performed.

Main results: 

Three studies were eligible for inclusion: two using amitriptyline (AMI) and one using citalopram. The studies recruited 223 children diagnosed with either Rome II or Rome III criteria.

For the primary outcome of treatment success, two studies used report of success on a symptom-based Likert scale, with either a two-point reduction or the two lowest levels defined as success. The other study defined success as a 15% improvement in Quality of life (QOL) rating scales, which could not be included in the meta-analysis due to the heterogeneity of the outcome measure. There is insufficient evidence to determine the effects of antidepressants compared with placebo on treatment success (risk ratio (RR) 1.17, 95% confidence interval (CI) [0.87 - 1.56]; 2 studies, 205 participants; low certainty evidence). We downgraded the evidence due to significant imprecision due to extremely sparse data.

We are uncertain whether children were more likely to withdraw due to adverse events with antidepressants or placebo, RR 3.80 (95% CI 0.61 - 23.57, very serious imprecision due to low events and number of participants. 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 for other outcomes of pain severity or frequency.

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