Oral Transmucosal Fentanyl Citrate for the Treatment of Migraine Headache Pain In Outpatients: A Case Series

Stephen H. Landy, MD


Headache. 2004;44(8) 

In This Article

Abstract and Introduction

Background: Migraine headache pain that does not respond to traditional antimigraine medications frequently requires treatment in the emergency department (ED) with parenteral opioids. Rapid onset of pain relief in an outpatient setting for migraine headache is the primary objective of patients and clinicians. Oral transmucosal fentanyl citrate (OTFC®; ACTIQ®) is a novel opioid product designed to deliver rapid analgesia to patients who experience breakthrough pain (BTP).
Objective: To evaluate the effectiveness, tolerability, and patient satisfaction with OTFC for the outpatient treatment of acute, refractory migraine headache pain.
Patients and Methods: Twenty patients with recurrent acute, refractory migraine headaches who had been referred to this headache clinic are reported in this case series. All patients had a history of tolerating parenteral opioids in the ED when experiencing refractory migraine pain and had been treated with outpatient opioid therapies in attempts to manage their migraine pain. Patients were prescribed OTFC (400 μg) as rescue treatment for moderate or severe migraine headache pain as outpatients. Patients were instructed to self-administer OTFC at home and complete a diary recording: pain intensity (11-point scale; 10 = worst pain imaginable to 0 = no pain) before and 15, 30, 60, and 120 minutes after OTFC; satisfaction with the effectiveness of OTFC (selecting 1 of 7 categories ranging from "very dissatisfied" through "very satisfied") rated at 120 minutes; and adverse events.
Results: Eighteen patients (13 female) experienced a migraine and self-administered OTFC. OTFC successfully treated migraine episodes in all 18 outpatients; no patient went to an ED. OTFC rapidly reduced pain intensity, with significant improvement at 15 minutes that was sustained and provided progressively more pain relief at 30, 60, and 120 minutes (all P< .01). Mean (SEM) pain intensity significantly declined from 8.83 (0.35) pretreatment to 2.28 (0.67) at 120 minutes, an average reduction of 75% (P< .01). Patients' satisfaction ratings with OTFC were overwhelmingly positive, with 94% being satisfied and more than half (56%) being "very satisfied." Three (17%) patients experienced nausea, two (11%) somnolence, and one (6%) each itching, vomiting, and dry mouth. All adverse events were mild or moderate in severity.
Conclusions: OTFC rapidly and significantly relieved acute, refractory migraine pain in outpatients, prevented the need for an ED visit, and was associated with high patient satisfaction ratings. The rapid onset of migraine headache pain relief in this case series is consistent with the analgesic effect reported with the use of OTFC in patients with BTP. OTFC was well tolerated in these patients who had a history of tolerating parenteral opioids in the ED when experiencing refractory migraine pain and had been treated with outpatient opioid therapies in attempts to manage their migraine pain. OTFC may be effective for outpatient treatment of acute, refractory migraine headache pain. Further controlled studies are warranted.

Migraine headache represents a therapeutic area in which rapid onset of analgesia and effective pain relief on an outpatient basis is the goal.[1] However, migraine headache pain can be so severe and disabling that migraineurs frequently seek crisis management in an emergency department (ED) when their usual outpatient treatments, such as serotonin (5-HT1) receptor agonists, nonopioid or opioid agents, fail to deliver rapid and effective analgesia. Approximately 50% of patients with migraine report visits to the ED for the acute treatment of refractory migraine pain,[2] regardless of the burdens associated with an ED visit. These burdens may include dependence on another person as driver and aide; costs; the prolonged wait for treatment; and the brightly lit, noisy environment that can worsen symptoms.[3,4]

While many treatments for refractory migraine headache are available in the ED, including parenteral opioids, antiemetics, and various other products for injection such as chlorpromazine, dihydroergotamine, droperidol, haloperidol, ketorolac, magnesium, metoclopramide, prochlorperazine, steroids, sumatriptan, and valproic acid, these medications, with the exception of subcutaneous sumitriptan, are not routinely prescribed for general outpatient use.[6,3,5]

Refractory migraine pain may be a similar clinical model to breakthrough pain (BTP) in that effective management frequently requires a rescue medication that has a rapid onset of action and allows dosing to be tailored to the individual characteristics of BTP episodes, such as intensity and duration. Oral transmucosal fentanyl citrate (OTFC®; ACTIQ®), a novel product designed to deliver rapid analgesia through direct absorption of fentanyl through the oral mucosa, may represent a rational option for outpatient treatment of refractory migraine headache pain. First, OTFC has been shown to be effective and well tolerated in the treatment of BTP, based on the results from clinical trials in opioid-tolerant cancer patients.[7,8,9,10,11] Second, OTFC is available in six dosage strengths (200, 400, 600, 800, 1200, and 1600 μg) to allow individualization of dosing, with the effective dose determined by titration.[8,11] Research has also provided evidence of the usefulness of OTFC, although at lower doses, in patients who are not regularly taking opiates.[12,13,14,15] In one double-blind study in nonopioid-tolerant postoperative patients, the median time to the onset of pain relief following OTFC was 5 minutes, which was comparable to that following IV morphine.[12] Thus, OTFC may provide a viable option for outpatients experiencing BTP or episodic pain due to other causes, including acute, refractory migraine headaches.

We assessed the effectiveness, tolerability, and patient satisfaction with OTFC as an outpatient treatment of acute, refractory migraine headache pain.


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