Using Mediation Analysis to Understand How Treatments for Paediatric Pain Work: A Systematic Review and Recommendations for Future Research.

Hayley B Leake,Michael A Wewege,Tasha R Stanton,Lauren C Heathcote,Joshua W Pate,G Lorimer Moseley,Hopin Lee

doi:10.3390/children8020147

Abstract

Clinicians have an increasing number of evidence-based interventions to treat pain in youth. Mediation analysis offers a way of investigating how interventions work, by examining the extent to which an intermediate variable, or mediator, explains the effect of an intervention. This systematic review examined studies that used mediation analysis to investigate mechanisms of interventions on pain-relevant outcomes for youth (3–18 years) with acute or chronic pain, and provides recommendations for future mediation research in this field. We searched five electronic databases for clinical trials or observational longitudinal studies that included a comparison group and conducted mediation analyses of interventions on youth and assessed pain outcomes. We found six studies (N = 635), which included a total of 53 mediation models examining how interventions affect pain-relevant outcomes for youth. Five studies were secondary analyses of randomized controlled trials of psychological interventions for chronic pain; one was a longitudinal observational study of morphine for acute pain. The pain conditions studied were irritable bowel syndrome, functional abdominal pain, juvenile fibromyalgia, mixed chronic pain, and post-operative pain. Fourteen putative mediators were tested, of which three partially mediated treatment effect; seven did not significantly mediate treatment effect and four had mixed results. Methodological and reporting limitations were common. There are substantial gaps in the field with respect to investigating, and therefore understanding, how paediatric interventions work.

Highlights

Pain is common in childhood and adolescence [1,2], presenting after an injury or procedure, as a consequence of disease, or without any identifiable cause [3]
Pain reactivity mediated the treatment effect of acceptance and commitment therapy (ACT) compared to a multidisciplinary treatment approach with amitriptyline (n = 30) for children and adolescents (10–18 years) with mixed chronic pain conditions, at reducing pain interference at 3.5-months and 7-months and depression at 3.5 months
Pain impairment beliefs mediated the treatment effect of ACT compared to a multidisciplinary treatment approach with amitriptyline (n = 30) for children and adolescents (10–18 years) with mixed chronic pain conditions, at reducing depression at 3.5-months and 7-months

Summary

Introduction

Pain is common in childhood and adolescence [1,2], presenting after an injury or procedure, as a consequence of disease, or without any identifiable cause [3]. Effective interventions for acute and chronic pain in young people are critically needed. Many interventions encompass a variety of single and multi-modal treatments including pharmacological, psychological, and physical interventions. The efficacy of such treatments for children and adolescents with acute pain and chronic has been reviewed (e.g., [4,5,6,7]). One potential explanation is that small effect sizes may represent wide variability in patient response, which could be addressed by better understanding the underlying mechanisms of treatment effects. Understanding treatment mechanisms would allow targets for paediatric pain interventions to be informed by empirical evidence, rather than presumptive theories. Clinicians would be able to refine and optimize the effectiveness of interventions by selectively targeting mechanisms known to improve outcomes [10]

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