Authors' objectives: Gabapentin is an anticonvulsant medication with a United Kingdom licence to treat partial seizures and neuropathic pain. It is used off-licence for acute pain and is frequently added to multimodal analgesic regimens after surgery to try and reduce opioid use while controlling pain effectively. To test the hypothesis that gabapentin reduces opioid use after major surgery and speeds up recovery, thereby reducing postoperative hospital length of stay compared to standard multimodal analgesia. Gabapentin is a medicine used to treat epilepsy and pain caused by damaged nerves. Doctors have recently been using gabapentin to treat pain after an operation, with the intention of reducing the amount of morphine-type drugs (called ‘opioids’) needed while maintaining good pain relief. Doctors want to try to reduce the amount of opioid drugs because they cause side effects (such as dizziness and reduced breathing rate), often delaying discharge from hospital and leading to slower recovery. There is uncertainty about whether adding gabapentin to the usual painkilling drugs will result in good pain relief, with fewer side effects, and therefore faster recovery after surgery. There are around 4.9 million episodes of surgery per year in the UK – 1.5 million of these are classified as major surgery, procedures which cost the NHS upwards of £5.5B per year. Up to 40% of patients report severe pain after surgery that negatively impacts their recovery. Optimal postoperative pain management not only meets the humanitarian imperative to alleviate suffering, but also provides benefits in terms of reduced length of hospital stay and reduced chronic postsurgical pain. These have consequent positive impacts on quality of life and well-being. Gabapentin is a medicine frequently added to multimodal analgesic regimens after surgery to try and reduce the use of opioid drugs (which can cause somnolence, dizziness and respiratory depression) while controlling pain effectively. It is an anticonvulsant medication with a UK licence to treat partial seizures and neuropathic pain. It is also used off-licence for acute pain. It reduces voltage-gated calcium channel activity in the central neurones and therefore reduces neuronal firing and neurotransmitter release. There are over 130 randomised controlled trials (RCTs) that have investigated gabapentin versus placebo in different surgical populations. Most are small (...

Authors' results and conclusions: One thousand one hundred and ninety-six (cardiac 500, thoracic 346, abdominal 350) participants consented and were randomised. Baseline characteristics were well balanced across the two groups: median age: 68 years; male sex 796/1195 (66.4%). Of the participants, 223/1195 (18.7%) did not receive all prescribed medication or received medication out of window. There was no difference in length of stay; median placebo (n = 589): 6.15, gabapentin (n = 595): 5.94 days [hazard ratio for discharge 1.07, 95% confidence interval (0.95 to 1.20), p = 0.26]. Opioid use in-hospital differed between surgical specialties (p = 0.001); in the abdominal specialty, it was significantly lower in the gabapentin group in 4 of the first 5 postoperative days [range −26% (−46% to 0%) to −36% (−52% to −14%)], with no differences in the cardiac specialty nor in the thoracic specialty beyond day 2. During follow-up, opioid use was similar in the two groups across all specialties. Acute pain beyond 24 hours was similar (p ≥ 0.15). The incidence of one or more serious adverse events was placebo: 189/595 (31.7%); gabapentin: 195/599 (32.6%). Health-related quality of life was similar [EQ-5D: mean difference −0.014 (−0.036 to 0.009), Short Form questionnaire-12 items physical component score: −0.87 (−1.71 to −0.04), Short Form questionnaire-12 items mental component score: at 4 weeks 0.74 (−1.71 to 0.42) and 4 months −0.55 (−1.61 to 0.51)]. Differences in costs and quality-adjusted life-years favoured placebo, and gabapentin was not considered cost-effective. Among patients undergoing major cardiac, thoracic and abdominal surgery, adding gabapentin to multimodal analgesic regimes did not result in a change in length of stay, opiate use in two specialties, acute pain, or health-related quality of life, nor was it cost-effective. Patient screening and recruitment Recruitment took place at seven NHS Secondary care centres. Between 12 April 2018 and 20 May 2022, 3405 patients were assessed for eligibility, of whom 2209 were excluded. Therefore, 1196 patients (cardiac 500, thoracic 346, abdominal 350) were recruited and randomised; 596 to placebo and 600 to the gabapentin group. The numbers in the two groups were well balanced across surgical specialties. Among patients undergoing major cardiac, thoracic and abdominal surgery, the addition of gabapentin (600 mg pr-operatively and 300 mg twice a day postoperatively for 48 hours) to multimodal analgesic regimes did not result in a change in hospital LoS, opiate use, acute pain, or quality of life, nor was it cost-effective.

Authors' methods: The GAP study was a multicentre, blinded, randomised controlled trial in patients aged ≥ 18 years, undergoing cardiac, thoracic or abdominal surgery with an expected postoperative stay of ≥ 2 days in seven National Health Service hospitals. The trial was designed to provide 90% power to detect a difference of 12.5% in the proportion of participants discharged by the median length of stay in each specialty (500 participants/specialty), which was reduced to 80% (340 participants/specialty) due to COVID-19-related recruitment challenges. Participants were randomised 1 : 1 (stratified by surgical specialty) to receive either gabapentin (600 mg before surgery, 300 mg twice daily for 2 days after surgery) or placebo as an adjunct to multimodal pain regimens. Primary outcome was length of stay. Secondary outcomes included acute and chronic (Brief Pain Inventory) pain, total opioid use, adverse health events, health-related quality of life (-EQ-5D-5L, Short Form questionnaire-12 items physical component score and mental component score), resource use; cost-effectiveness (outcome measure quality-adjusted life-years using EQ-5D, five-level version). GAP study tests the application of gabapentin to major body cavity surgery, but not major non-body cavity surgery, or non-major surgery. The fixed dose and limited duration of gabapentin may reduce applicability to certain populations. Reducing the power to 80% reduced the ability of the trial to detect a beneficial effect of gabapentin. Study design A multicentre, parallel-group, placebo-controlled, pragmatic RCT comparing the effectiveness, cost-effectiveness and safety of gabapentin as an adjunct to standard multimodal analgesia. Settings and participants Participants were recruited from three surgical specialties (cardiac, thoracic and abdominal) in NHS secondary care centres. They were ≥ 18 years of age undergoing non-emergency surgery and were expected to stay in hospital and be able to swallow for at least 2 days after their surgery. Participants were excluded if they were already taking gabapentinoids or other anti-epileptics or receiving planned epidural anaesthesia/analgesia. The trial intervention was 600 mg gabapentin – two capsules – given preoperatively and 600 mg/day (300 mg in the morning and 300 mg in the evening) given postoperatively for 2 days when clinically able to swallow following extubation, within the multimodal analgesic regimens specified by local analgesic protocols. The comparator was a placebo capsule taken at the same time points as the active tablet.

Project Status: Completed

URL for project: https://www.journalslibrary.nihr.ac.uk/programmes/hta/15/101/16

Year Published: 2026

URL for published report: https://www.journalslibrary.nihr.ac.uk/hta/PLMH9787

URL for additional information: English

English language abstract: An English language summary is available

Publication Type: Full HTA

Country: England, United Kingdom

DOI: 10.3310/PLMH9787

Organisation Name: NIHR Health Technology Assessment programme

Contact Address: NIHR Journals Library, National Institute for Health and Care Research, Evaluation, Trials and Studies Coordinating Centre, Alpha House, University of Southampton Science Park, Southampton SO16 7NS, UK

Contact Name: journals.library@nihr.ac.uk

Contact Email: journals.library@nihr.ac.uk