To identify the efficacy of cyclooxygenase-2 (COX-2) inhibitors (COXIBs) for headache in acute brain injury (ABI).

Headache after ABI is common; yet, treatment options are limited and heavily rely on opioids. COX-2 is overexpressed in ABI and responsible for inducing pain. Hence, COXIBs may be a promising and potentially opioid-sparing therapeutic option for headache following ABI.

We performed a systematic review through MEDLINE and Embase databases spanning 08/2021-09/2023. Interventional and observational studies assessing headache in adult patients with ABI were included. Each article was reviewed by two independent reviewers using Distiller SR®. Data were synthesized through descriptive statistics. A meta-analysis was unfeasible due to study heterogeneity.

Of 3193 articles, 6 met inclusion criteria: 4 randomized controlled trials and 2 retrospective cohort studies, all conducted in neurosurgical patients (n=913). Five studies used COXIBs in the intervention group only; one reported reduction in overall 10-point visual analog scale (VAS) (mean±SD [3.8±0.9 vs 5.3±1.3]) and morphine use (median[range] 6[0-18] vs 10[0-40] mg); another reported reduction in 10-point VAS (mean [3.5/3.2/2.9 vs 4.2/4.0/3.6]) and morphine equivalent units (mean [1.2/0.8/1.6/4.6 vs 11.6/13.0/12.6/45.2]) at overall time intervals; one showed reduction in 100-point VAS (mean±SEM [25±3 vs 38±4]) and morphine use (mean±SEM [0.8±0.3 vs 2.7±0.8] mg) at only 1 time interval; one reported reduction in 10-point numeral pain scores (NRS) in 3 time intervals (mean [2.5/2.0/1.8 vs 3.0/2.5/2.0]) but did not assess opioid use; and one did not find any reduction in VAS or opioid use. One study which assessed dexmedetomidine and ropivacaine as adjuncts and used COXIBs in both groups, reported reduction in pain in the intervention group.

In post-neurosurgical patients, COXIBs might be a promising opioid-sparing adjunctive therapy for headache. Given the overall limited data available, evidence to establish their efficacy will require additional research including other forms of ABI.