The efficacy of pregabalin and gabapentin in managing headache following subarachnoid hemorrhage: a systematic review

Abstract

Background: Subarachnoid hemorrhage (SAH) is a life-threatening emergency condition often accompanied by severe, sudden-onset headache. The main causes are head trauma and aneurysm rupture. Pain management in these patients remains challenging, typically requiring opioids which carry significant adverse effects. As anti-neuropathic agents, gabapentin and pregabalin may serve as suitable alternatives to opioids. This systematic review aimed to evaluate the efficacy and safety of gabapentin and pregabalin in managing SAH-associated headaches. Methods: Following PRISMA guidelines, we conducted comprehensive searches in PubMed, SCOPUS, Web of Science, and EMBASE through May 2025. Key search terms included "Gabapentin," "Pregabalin," "Subarachnoid Hemorrhage," and "Headache." After initial screening, we selected English or Persian-language articles investigating these medications' effects on SAH-related headache. After removal of duplicates and screening, four eligible studies (including randomized controlled trials and cohort studies) were included for final analysis. Data on study type, sample size, type of interventions, headache management-related outcomes, as well as safety and tolerability profiles were extracted. Results: Pregabalin demonstrated significant efficacy, showing a statistically significant reduction in pain intensity compared to placebo before anesthesia induction (P≤0.004) and up to 24 hours post-operatively (P=0.007). Additionally, patients receiving pregabalin required significantly fewer rescue analgesics (P≤0.005). In contrast, gabapentin did not produce a statistically significant reduction in pain intensity or morphine equivalent requirements compared to placebo, although a non-significant trend toward decreased pain was observed. Safety profiles were favorable for both medications; no serious adverse events leading to drug discontinuation were reported. Conclusion: Pregabalin appears to be an effective, safe, and well-tolerated option for managing SAH-related headache, significantly reducing both pain intensity and opioid requirements. Current evidence for gabapentin remains limited and inconclusive, warranting further large-scale, randomized controlled trials to confirm its potential role in this setting. Copyright © 2025 Saadatnia et al. Published by Tehran University of Medical Sciences. CC BY NC This work is licensed under a Creative Commons Attribution-Non-Commercial 4.0 International license (https://creativecommons.org/licenses/by-nc/4.0/). Non-commercial uses of the work are permitted, provided the original work is properly cited.