Gabapentin for Headache in Aneurysmal Subarachnoid Hemorrhage

The purpose of this study is to see how much gabapentin will reduce headaches associated with subarachnoid hemorrhage (SAH) and to reduce the amount of narcotic pain medication prescribed.

The investigators plan to use gabapentin (GBP), an FDA approved non-narcotic pain medication for neuropathic pain, which is also an alpha-2-delta (A2DR) receptor analogue to reduce the pain and decrease the need for narcotics in patients with aneurysmal subarachnoid hemorrhage (aSAH). GBP has been shown to decrease neuropathic and non-neuropathic pain in a variety of perioperative and postoperative conditions. A2DR affinity also has some neuroprotective effect in animal data. The investigators plan to conduct a prospective, double-blinded, randomized trial to further assess GBP-associated reductions in narcotic use and pain scores compared to the non-GBP (placebo) arm. To accomplish this aim, the investigators plan to randomize 20 aSAH patients with headache to either GBP and standard of care pain treatment versus placebo and standard of care treatment.

Gabapentin capsules 100 mg ter in die (TID), 200 mg TID, 300 mg TID, 400 mg TID, 600 mg TID, 900 mg TID.

Placebo capsules 100 mg ter in die (TID), 200 mg TID, 300 mg TID, 400 mg TID, 600 mg TID, 900 mg TID.

Gabapentin capsules will be administered orally and titrated from 100 mg - 900 mg TID based on the patient's numeric pain score and creatinine clearance. Both groups will receive other standard of care pain medications.

Placebo capsules will be administered orally and titrated from 100 mg - 900 mg TID based on the patient's numeric pain score and creatinine clearance. Both groups will receive other standard of care pain medications.

Pain was measured on a Visual Analogue Scale (VAS) rated from 0-10, where 0 was no pain and 10 was the worst pain imaginable. The numeric pain score was measured every 4 hours and the total score over 24 hours was averaged as the daily numeric pain score. The daily scores were then averaged over a 7 day period for a single average pain score.

The amount of narcotics administered, averaged over a 7 day period, calculated in total morphine equivalents (ME).

The Brigham and Women's Hospital Management of Post-operative Pain Patients discharge questionnaire (BWQ) was used to measure pain control satisfaction. The questionnaire was modified and transformed into a uniform scale so all numbers were on the same direction. Subjects were asked to answer six questions on a score of 0-5, for a total possible range of 0-30. A lower score indicated a better outcome (less pain) and higher pain control satisfaction and a higher score indicated a worse outcome (more pain) and lower pain control satisfaction.

Inclusion Criteria: 18 years of age or older Have aneurysmal subarachnoid hemorrhage (aSAH) diagnosed by CT scan of the brain and/or angiogram evidence of intracranial aneurysm (CTA or digital subtraction angiogram or MRA) Have symptomatic headache Able to swallow and verbalize pain score No known allergy to gabapentin or fentanyl Numeric pain score ≥ 5 Ability to provide written personal consent Exclusion Criteria: Gabapentin use prior to SAH admission Renal failure with creatinine clearance less than 30 mL/min Unable to receive standard of care pain medications Pregnant or breastfeeding patients History of severe depression defined by the Diagnostic and Statistical Manual of Mental Disorders, 4th Edition, Text Revision (DSM IV)

Dhakal LP, Turnbull MT, Jackson DA, Edwards E, Hodge DO, Thottempudi N, Kamireddi P, Akinduro OO, Miller DA, Meschia JF, Freeman WD. Safety, Tolerability, and Efficacy of Pain Reduction by Gabapentin for Acute Headache and Meningismus After Aneurysmal Subarachnoid Hemorrhage: A Pilot Study. Front Neurol. 2020 Jul 28;11:744. doi: 10.3389/fneur.2020.00744. eCollection 2020.