Safety, Tolerability, and Efficacy of Pain Reduction by Gabapentin for Acute Headache and Meningismus After Aneurysmal Subarachnoid Hemorrhage: A Pilot Study

Abstract

Introduction: Severe, often sudden-onset headache is the principal presenting symptoms of aneurysmal subarachnoid hemorrhage (aSAH). We hypothesized that gabapentin would be safe and tolerable for aSAH-induced headaches and would reduce concurrent opioid use. Methods: We performed a single-center, double-blind, randomized, placebo-controlled trial (registered at ClinicalTrials.gov; NCT02330094) from November 24, 2014, to June 24, 2017, where aSAH patients received either dose-escalating gabapentin or oral placebo, both alongside a standard of care pain regimen. After 7 days, patients had the option to continue in an open-label period until 14 days after enrollment or until discharge from the intensive care unit. Our primary endpoint was the efficacy of gabapentin in reducing headache numeric pain scores and opioid usage in patients with aSAH compared to the placebo group. We identified 63 potential patients with aSAH for the study. After applying stringent exclusion criteria, 16 eligible patients were enrolled into one of two arms. Results: The study ended prematurely after reaching a pre-specified funding period and an unexpected drop in aSAH cases. There was a trend toward lower headache numeric pain scores and opioid use in the gabapentin treated arm; however this was not significantly different. Gabapentin was well tolerated by participants and no adverse effects were reported. Conclusions: While there was a trend toward lower pain scores and opioid requirement in the gabapentin group, the study was underpowered to detect a difference. Larger multicenter trials are required to evaluate the efficacy of gabapentin to reduce opioid requirements after aSAH.

Keywords: aneurysmal subarachnoid hemorrhage; gabapentin; headache; numeric pain scores; opioid.

Copyright © 2020 Dhakal, Turnbull, Jackson, Edwards, Hodge, Thottempudi, Kamireddi, Akinduro, Miller, Meschia and Freeman.

Figures

Figure 1

Comparison of median average numeric pain score (NPS) and IV morphine equivalent per day between gabapentin and placebo groups. (A) Median average NPS between groups for the first 7 days. (B) Box graphs of median average NPS at baseline compared to day 7 for gabapentin and placebo groups. (C) Median average NPS between groups over 14 days. (D) Median IV morphine equivalent between groups for first 7 days. (E) Box graphs of median IV morphine equivalent at baseline compared to day 7 for gabapentin and placebo groups. (F) Median IV morphine equivalent between groups over 14 days. IV indicates intravenous; NPS, numeric pain score.

Figure 2

Increasing median gabapentin dose over first 7 days.

Figure 3

Pathophysiologic mechanisms of headache and meningeal irritation after subarachnoid hemorrhage and other common causes, such as migraine and cervicogenic headache. CGRP indicates calcitonin gene-related peptide; CSF, cerebrospinal fluid; ICP, intracranial pressure. Used with permission of Mayo Foundation for Medical Education and Research. All rights reserved.