Once Daily Gastroretentive Gabapentin Formulation for Episodic Migraine Prophylaxis: The First Case Report

Presented at the International Headache Congress, hosted by the International Headache Society and the American Headache Society (June 27 - 30, 2013 in Boston, MA):

Once Daily Gastroretentive Gabapentin Formulation for Episodic Migraine Prophylaxis: The First Case Report

Daniel Kantor, MD

Objectives:  

To report the use of a once daily gastroretentive gabapentin (G-GR) formulation for the prophylaxis of episodic migraine.

Background:  

Gabapentin is a calcium channel α2δ ligand that increases γ-aminobutyric acid (GABA) concentrations in the brain; it has been hypothesized to play a role in migraine prophylaxis. However, according to the 2012 updated evidence-based guideline report of the Quality Standards Subcommittee of the American Academy of Neurology and American Headache Society, the evidence is conflicting or inadequate to support or refute the use of gabapentin for migraine prevention (Level U recommendation). There are known side effects and limitations to the use of immediate release gabapentin (G-IR), and the conflicting data may be due to the difficulty in patients attaining and sustaining optimal dosages (due to side effects and frequency of administration). Gralise^® is a once daily G-GR formulation approved by the U.S. Food and Drug Administration (FDA) for the management of postherpetic neuralgia (PHN); PHN patients seem to respond to G-GR without the same burden of side effects that limit dose titration of G-IR. We hypothesized that G-GR may play a beneficial role in the prophylaxis of episodic migraine.

Methods: 

Case report.

Results:  

A 36-year-old woman with a 15-year history of episodic migraines without aura (frequency 7 migraines/month, intensity 4-6/10) presented to a headache specialist; her body-mass index (BMI) was 27 kg/m². In the past, she had attempted topiramate (up to a dose of 200 mg/day), which was discontinued secondary to cognitive side effects and propranolol 80 mg three times a day, which was discontinued due to hypotension. She refused to attempt antidepressants for migraine prophylaxis due to her concerns regarding the potential for neuropsychiatric side effects. G-GR was initiated at 300 mg with her evening meal, and it was titrated up over 2 weeks to 1800 mg with her evening meal. The patient denied any side effects and within the first month of treatment, her migraine frequency reduced to 3 migraines/month (average intensity 3/10). By the third month of treatment, her migraine frequency had reduced to 1–2 migraines/month (average intensity 2-3/10). 6 months after initiation of G-GR, her migraine frequency remains at 1 migraine/month (average intensity 2/10). The patient denies any treatment-emergent side effects and is satisfied with her migraine prophylaxis

Conclusions:  

This case report suggests that G-GR should be further studied in case series, prospective open-label studies and, eventually, randomized double-blind placebo controlled trials for the prophylaxis of episodic migraines. Our patient may respond even further with escalating doses of G-GR beyond 1800 mg a day, and perhaps with administration with the morning, rather than evening, meal or even twice a day (with breakfast and dinner) dosing. However, dosing deviations from that approved for PHN may have the disadvantage of increased side effects. Dose finding trials, including serial measurement of serum gabapentin, will be invaluable in helping to elucidate the potential role of G-GR in the prophylaxis of episodic migraines.


Selected References:

Argoff, Chen C and Cowles VE. Clinical development of a once-daily gastroretentive formulation of gabapentin for treatment of postherpetic neuralgia: an overview. Expert Opin Drug Deliv 2012;9(9):1147-60.

Mathew NT, Rapoport A, Saper J, et al. Efficacy of gabapentin in migraine prophylaxis. Headache 2001;41:119–128.

Silberstein SD. Practice parameter: evidence-based guidelines for migraine headache (an evidence-based review): report of the Quality Standards Subcommittee of the American Academy of Neurology. Neurology 2000;55: 754–762.

Silberstein SD. Preventive migraine treatment. Neurologic Clinics 2009;27:429-43.

Silberstein SD, Holland S, Freitag F, et al. Evidence-based guideline update: Pharmacologic treatment for episodic migraine prevention in adults. Neurology 2012;78:1337-1345.