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

Methods

This manuscript adheres to the Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines.[14]

Review Question, Definitions, and Protocol

The primary outcome, for which conclusions about the effects of the interventions under review would largely be based, was the proportion of children and adolescents experiencing an analgesic effect of gabapentin or pregabalin for pain as described in the original study. Pain included acute pain, perioperative pain, chronic pain, and recurrent pain.

The secondary outcomes were all other outcomes pertaining to the use of gabapentin or pregabalin, as described in the original studies, including proxy measures of pain measurement (such as the volume of analgesic required), and the proportion of children and adolescents experiencing adverse effect events related to the intervention.

An a priori protocol was not registered in advance of conduct of this systematic review.

Search Strategy

Searches were conducted in 4 bibliographic databases: Embase 2017 (Supplemental Digital Content 1, Table 1, http://links.lww.com/AA/C650), US National Library of Medicine (MEDLINE) 2017, Scopus 2017, and Web of Science 2017, on November 22, 2017.

The following search strategy was used in Web of Science:

  • #1 Topic = (Gabapentin* or pregabalin* or Neurontin or Lyrica).

  • #2 Topic = (pain* or neuralgi* or neuropath* or analgesi*).

  • #3 Topic = (child* or adolescent* or "young adult*" or infant* or youth* or boy* or girl* or toddler* or newborn* or neonat* or pediatric*).

  • #4 #3 AND #2 AND #1.

Similar search strategies were constructed for Embase, MEDLINE, and Scopus. Both the Cochrane Central Register of Controlled Trials and the International Standard Randomized Controlled Trial Number website (http://www.isrctn.com) were reviewed to further identify any relevant completed, ongoing, or recently completed randomized controlled trials. There was no limitation by date, and only publications in English were included. The reference lists of studies and review articles were checked for any additional randomized controlled trials.

Study Inclusion Criteria and Relevance Screening

Randomized controlled trials that investigated the analgesic effects of gabapentin or pregabalin (all doses and any routes of administration) only in children and adolescents <18 years of age, published as a full journal article, were eligible for inclusion. Only English language articles were included. Studies that included an active or placebo comparator were eligible. Nonrandomized trials, cohort, case–control, cross-sectional, and case report designs were excluded. Screening was performed using Covidence software (Covidence systematic review software; Veritas Health Innovation, Melbourne, Australia).

For each reference identified by the search, 2 reviewers (O.E. and C.E.W.) independently assessed eligibility against the selection criteria defined a priori. References that appeared to meet the inclusion criteria were retrieved in full-text format and further assessed by the same 2 reviewers independently. Following discussion, there was good agreement regarding screening decisions between the 2 reviewers, and it was therefore not necessary to consult a third reviewer to obtain consensus.

Methodological Assessment and Data Extraction

Two reviewers (O.E. and C.E.W.) independently conducted data extraction regarding study characteristics, population characteristics, the interventions/comparators, and outcomes directly into Excel (Microsoft Version 16.11.1, Chicago, IL). No attempts were made to contact primary authors if data were incomplete, and no studies were identified as duplicates. Discrepancies in data extraction between the 2 reviewers were resolved by discussion.

The methodological quality of the eligible studies was assessed independently by 2 reviewers (O.E. and C.E.W.), based on the Cochrane Handbook for Systematic Reviews of Interventions.[15] The domains assessed included (1) methods of randomization, (2) allocation concealment, (3) blinding of the outcome assessors, (4) blinding of the study participants, (5) presence of incomplete data, (6) selective reporting, (7) acknowledgement of financial support, and (8) other sources of methodological shortcomings. Data for each domain were entered into Covidence, and each study was classified as high, unclear, or low methodological quality such that if 1 domain was not met, the trial was considered a high risk of methodological shortcomings, and if 1 domain was unclear, the trial was considered to have an unclear risk of methodological shortcomings. Discrepancies in methodological quality assessment were resolved by discussion.

Statistical Analysis

Due to the heterogeneity of study outcomes, reported summary measures were not produced and the original results for each study were described.

Comments

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