Systematic Review of the Efficacy and Safety of Gabapentin and Pregabalin for Pain in Children and Adolescents

Oluwaseun Egunsola, PhD; Claire E. Wylie, PhD; Kate M. Chitty, PhD; Nicholas A. Buckley, MD

Disclosures

Anesth Analg. 2019;128(4):811-819. 

In This Article

Abstract and Introduction

Abstract

The barriers to opioid use in some countries necessitate the need to identify suitable alternatives or adjuncts for pain relief. The gabapentinoids (gabapentin and pregabalin) are approved for the management of persistent pain in adults, but not in children. Searches were conducted in Embase, Medline, Scopus, and Web of Science up until November 2017, for randomized controlled trials that investigated the analgesic effects of gabapentin or pregabalin in children and adolescents <18 years of age. A total of 7 publications were identified, 5 regarding gabapentin as prophylactic postsurgical pain relief for either adenotonsillectomy (n = 3) or scoliosis surgery (n = 2), and 1 for gabapentin treatment of chronic regional pain syndrome/neuropathic pain. One study investigated the efficacy of pregabalin as a treatment for fibromyalgia. Based on the studies' primary outcomes alone, neither of the chronic pain studies involving gabapentin and pregabalin showed significant efficacy compared with amitriptyline or placebo, respectively. Two of the prophylactic gabapentin studies for adenotonsillectomy and idiopathic scoliosis surgery reported significantly fewer children requiring analgesia and lower opioid requirement, respectively, compared with placebo. Two of the identified clinical trials (conducted by the same first author) on the efficacy of gabapentin for prophylactic postadenotonsillectomy pain relief were omitted from narrative synthesis due to clear evidence of fabricated data. Overall, this review identified a paucity of evidence for the analgesic effect and safety of gabapentinoids in children. We also suggest audit of any current evidence-based practice and clinical guidelines that have cited the research studies with fabricated data.

Introduction

Pain is a common experience in children and adolescents, the prevalence varying between 4% and 80% depending on the type of pain and the method of assessment.[1] Pain can be neuropathic from nerve compression or disruption or nociceptive from inflammation or tissue injury.[2] The World Health Organisation recommends a 2-step management strategy involving analgesic selection based on the level of pain severity,[2] for persistent pain in children and adolescents.

The gabapentinoids (gabapentin and pregabalin) are structural analogues of γ-aminobutyric acid, which are therapeutic alternatives or adjuncts for the management of persistent pain in adults for whom they are the first-line treatment for neuropathic pain.[3] They are also recommended by the American Pain Society and the American Society of Anaesthesiologists as components of multimodal postoperative pain therapy.[4] Their analgesic effect is achieved by binding to the α2δ-1 subunits of voltage-gated calcium channels, which control excitatory neurotransmitter release.[5] Evidence from adult studies suggests that gabapentinoids may reduce the incidence of postoperative adverse drug effects in comparison to other options for multimodal postsurgical analgesia such as opioids,[6] as well as reducing opioid requirements and pain scores.[7]

A recent systematic review evaluated the efficacy and safety of antiepileptic drugs for pain in children and adolescents; however, only 2 studies, 1 each for gabapentin and pregabalin, were included.[8] Furthermore, the review did not include children receiving prophylactic gabapentinoids for postoperative pain. Currently, the most common treatment choices for postoperative analgesia in children are systemic opioids, nonsteroidal anti-inflammatory drugs, and regional analgesia.[9] There are, however, barriers to opioid use in several developing countries, where limited financial resources, strict regulations, concerns about diversion, and difficulties with procurement[10,11] necessitate the need to identify suitable alternatives or adjuncts for pain relief. Although gabapentin is approved for the treatment of epilepsy in children, the safety and efficacy for neuropathic and postoperative pain in children and adolescents have not been established.[12] Similarly, the safety and efficacy of pregabalin have not been established in children and adolescents with either epilepsy or pain.[13]

This systematic review aims to examine the current evidence for the efficacy and safety of gabapentin and pregabalin for pain management in children and adolescents.

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