Arthur Jeske DMD, PhD; James Zahrowski DMD, MS, PharmD
Gabapentin (250 mg) is statistically superior to placebo for treating established acute postoperative pain. However, to achieve at least 50 percent pain relief over six hours, the number of patients needed to treat was 11, which suggests gabapentin has limited clinical value and is inferior to common analgesics.
For adults with established acute postoperative pain, how safe and effective is a single oral dose of gabapentin as compared to placebo?
The authors searched four electronic databases for studies published to August 2009. They sought additional studies from lists of retrieved articles and reviews. They followed a clearly defined protocol. Two independent authors assessed trial quality and extracted data. To determine the relative benefit (RB), risk ratio (RR) and number-needed-to-treat-to-benefit (NNT), they extracted data for both total pain relief (TOTPAR) and summed pain intensity difference (SPID). The authors also acquired data about the number of participants needing rescue medication, the time that elapsed before rescue medication was administered, as well as information on adverse events and subject withdrawals.
The review identified four unpublished studies of the analgesic effect of a single oral dose of gabapentin (228 participants in three dental studies and 99 in one orthopedic study) versus placebo (172 participants). One study that evaluated gabapentin at 500-mg doses (21 participants) provided insufficient data for analysis. Three studies that evaluated 250-mg doses of gabapentin provided data suitable for pooling. Fifteen percent of participants experienced at least 50 percent pain relief over six hours with gabapentin at a 250 mg-dose compared with 5 percent of participants in the placebo group. The RB of gabapentin treatment versus placebo was 2.5 (95 percent confidence interval [CI], 1.2 to 5) with an NNT of 11 (95 percent CI, 6.4 to 35). Rescue medication was needed by 69 percent and 86 percent of participants receiving gabapentin and placebo, respectively. Time-to-rescue medication averaged 2.4 hours in the gabapentin groups and 2.1 hours for the placebo groups. Adverse effects were not observed in three of four studies, and the two serious ones reported occurred in participants receiving placebo.
A limited amount of high-quality evidence suggests that gabapentin (single oral dose at 250 mg) is inferior to other analgesics for treating acute postoperative pain. A limited number of patients derive pain relief from gabapentin, which also appears to be well-tolerated in singe doses.
Source of Funding:
Internal sources: Oxford Pain Research Funds UK. External sources: NHS Cochrane Collaboration Grant UK, NIHR Biomedical Research Centre Programme UK, UK National Institute of Health Research UK. The authors indicated research suppot from charities, government, academic and industry sources.
Importance and Context:
Gabapentin is used in the treatment of seizures, post-herpetic neuralgia, and other neuropathies. The authors of the review state the drug is thought to possessanti-seizure, analgesic and anxiolytic effects. (1) There is no evidence that gabapentin analgesia is dose related. However, adverse events associated with the CNS-depressant effects of the drug appear to be dose related. The use of gabapentin for nociceptive pain is uncommon and of questionable efficacy.
Strengths and Weaknesses of the Systematic Review:
This high-quality systematic review included a comprehensive search, defined inclusion and exclusion criteria, and had no language restrictions. The authors did not search abstracts, conference proceedings or other grey literature. Unpublished trial data from pharmaceutical manufacturers was not sought. Two authors independently assessed trial quality and extracted data. Disagreements were resolved through consensus or by a third author. The authors followed standard guidelines for data and heterogeneity analyses. The authors acknowledged support from government and industry sources. Only four unpublished studies met the inclusion criteria, 3 for dental pain and one for orthopedic surgical pain.
Strengths and Weaknesses of the Evidence:
The review included four studies that were not published but which received a maximum score of five on the Oxford Quality Scale. All studies were of high quality, all were randomized and double-blinded to minimize bias, and all met the inclusion criteria set for the review. Most of the studies (3 of 4) evaluated single doses of gabapentin (250 mg). Because of insufficient data, the authors neither compared dose-response relationships nor pain `model effects. Data were sufficient for evaluating need for rescue medication, time to rescue medication, adverse event and subject withdrawals.
Implications for Dental Practice:
Based on as safety and efficacy outcomes and NNT measures, single oral doses of gabapentin (250 mg) are inferior to single doses of conventional NSAIDs, which remain the drug of first choice for adults with acute, moderate-to-severe postoperative pain. Gabapentin may be used in the treatment of seizure disorders and in the management of chronic neuropathic pain, an understanding of its role in managing acute post-operative pain will require more research with a greater emphasis on dose-response analyses or perhaps in combination with other conventional analgesics.
1. Kong VK, Irwin Mg. Gabapentin: a multimodal perioperative drug? Brit. J. Anes. 2007;99(6):775-86.