Efficacy of Cyclooxygenase-2 Inhibitors for Headache in Acute Brain Injury: A Systematic Review.

Background: Headache management after acute brain injury (ABI) is challenging. While opioids are commonly used, selective cyclooxygenase-2 inhibitors (COXIBs) may be promising alternatives. However, concerns about cardiovascular effects and bleeding risk have limited their use. We aimed at summarizing available data on efficacy of COXIBs for headache management following ABI. Methods: A systematic review was conducted through MEDLINE and Embase for articles published through 09/2023 (PROSPERO CRD42022320453). No language filters were applied to the initial searches. Interventional or observational studies and systematic reviews assessing efficacy of COXIBs for headache in adults with ABI were eligible. Article selection was performed by two independent reviewers using Distiller SR®. Descriptive statistics were used for data analysis, while meta-analysis was unfeasible due to study heterogeneity. Results: Of 3190 articles identified, six studies met inclusion criteria: four randomized controlled trials and two retrospective cohort studies, all conducted in neurosurgical patients (total n=738) between 2006-2022. Five studies used COXIBs in the intervention group only. Of the six studies, four found a reduction in overall pain scores in the intervention group, while one showed improvement only at 6 hours postoperative, and one did not find significant differences. Pain scores decreased between 4-15%, the largest shift being from moderate to mild severity. Three studies found an overall opioid use reduction throughout hospitalization in the intervention group, while one reported a reduction at 12 hours postoperative only. Opioid consumption decreased between 9-90%. Two studies found a decrease in hospital-length-of-stay by ~1 day in the intervention group. The one study reporting postoperative hemorrhage found a statistically non-significant 3% reduction in the intervention group. Conclusions: In adults with ABI, COXIBs may serve as opioid-sparing adjunctive analgesics for headache control, with limited but pointed data to indicate efficacy in the post-neurosurgical setting. However, further safety data remains to be elucidated.