IV Lidocaine Relieves Pain in Refractory Migraine

 Lidocaine infusions yield both short- and medium-term pain relief in treatment-resistant chronic migraine, new research suggests.

Investigators analyzed data for more than 600 hospitalized patients with refractory chronic migraine receiving continuous multiday lidocaine infusions. Results showed median pain rating decreased by 6 points on the Numerical Rating Scale (NRS) from admission to end of hospitalization.

In addition, almost 90% of patients responded acutely, with 43% achieving sustained improvement at 1 month.

"Our main messages are that lidocaine can produce acute relief of headache pain, and on average, patients in the study reported some relief up to a month or greater after treatment," study investigator Eric Schwenk, MD, associate professor of anesthesiology and orthopedic surgery and director of orthopedic anesthesia, Sidney Kimmel Medical College at Thomas Jefferson University, Philadelphia, Pennsylvania, told Medscape Medical News.

The findings were published online May 23 in BMJ Regional Anesthesia and Pain Medicine.

Adequate Evidence?

Inpatient hospitalization for treatment with multiday intravenous infusions is indicated for patients with refractory chronic migraine, the investigators note.

Continuous multiday lidocaine infusion has been suggested for these patients. Although the exact mechanism of action is unknown, it appears its anti-nociceptive, anti-hyperalgesic, and anti-inflammatory effects "play a key role," the researchers write.

Schwenk said he conducted the study because patients with resistant migraine "have very few treatments to turn to that can produce meaningful improvement in their headache pain." He added that this type of migraine is usually associated with some degree of disability.

At Thomas Jefferson, intravenous therapies such as lidocaine infusions "have been used successfully for several decades, but very few studies have been published that show any benefit of lidocaine," he said.

"We wanted to describe our experience with lidocaine and demonstrate the benefits on headache pain that occur. We also wanted to show that there is adequate evidence to support a clinical trial, which is the gold standard in medicine, that examines lidocaine in chronic migraine," Schwenk added.

The researchers assessed the electronic records of all consecutive inpatients with refractory chronic migraine who had sufficient information in their charts and who were treated with continuous lidocaine infusion between April 1, 2017 and April 1, 2020. The analysis included 609 patients (mean age, 46  years; 81.1% women; 89.8% White, 6.4% Black, 2% Hispanic).

In addition to the infusion, patients received other migraine medications during hospitalization, including ketorolac, magnesium, dihydroergotamine, methylprednisolone, and neuroleptics.

The primary outcome was change in headache pain from baseline to hospital discharge. Secondary outcomes, measured at the postdischarge office visit 25 to 65 days after treatment, included headache pain, number of headache days, percentage of sustained and acute responders, plasma lidocaine levels, and drug-related adverse effects (AEs).

Not For Everyone

Results showed baseline current pain ratings for all hospitalized patients decreased from a median of 7.0 (5 - 8) on admission to 1.0 (0 - 3) on discharge (P < .001) on the NRS. On the scale, a zero is defined as "no pain" and a 10 is "worst pain imaginable."

The average pain at the post-discharge office visit likewise decreased from baseline (5.5 vs 7.0 [5.0 - 8.0], P < .001). Moreover, the number of headache days decreased from baseline to the postdischarge office visit (26.8 vs 22.5 day, P < .001).

The researchers also distinguished between "acute" (86.8%) and "sustained" (46.2%) responders, with some overlap. Acute responders reported a decreased of 2 points or more on the NRS from beginning to end of treatment. Sustained responders were "those acute responders whose average pain remained at a level 2 points below baseline at 1 month," the investigators write.

A subgroup analysis of 244 patients who had received lidocaine previously showed no difference in headache days at the postdischarge office visit between them and the participants who had not previously received lidocaine.

Patients who received ketorolac or methylprednisolone during their hospitalization had a smaller change in pain compared with those who did not receive these agents. There were no significant differences in patients who received other headache medications.

The most common adverse event was nausea/vomiting. This was followed by cardiovascular changes, hallucinations/nightmares/visual changes, sedation/sleepiness, anxiety, dizziness/lightheadedness, cerebrovascular accident-like symptoms, urinary retention, and paresthesias.

"Lidocaine is not for everyone and does have some side effects such as nausea/vomiting, heart rhythm changes, and vision changes," said Schwenk.

Additionally, "in our study it required an average of 5 days of continuous infusion through an intravenous line to be effective and has not been well studied in patients with less severe disease," he noted.

Nevertheless, "for patients with refractory chronic migraine and their physicians, it may be worth considering referral to an experienced center that can offer aggressive intravenous treatments such as lidocaine if relief cannot be obtained from other medications," he said.

The investigators add that a "prospective, randomized, double-blind trial is needed to confirm these results but may be challenging, given the refractory nature of the disease and the associated ethical dilemmas."

"Valuable Evidence"

Commenting for Medscape Medical News, Samer Narouze, MD, PhD, professor and chair, Center for Pain Medicine, Western Reserve Hospital, Cuyahoga Falls, Ohio, "congratulated" the investigators on the research. He was not involved with the study.

He described the paper as "an important step in the search for an effective treatment for intractable chronic migraine headaches, which are otherwise refractory to other medications."

However, Narouze, who is also the president of the American Society of Regional Anesthesia and Pain Medicine, pointed to several limitations to adopting the described protocol.

First, the researchers used continuous infusions for several days with hospitalization, which "may significantly add to the treatment costs and may not be feasible or practical for wide adoption by many," he said. In addition, the "great outcomes reported in this study" may not be reproducible with outpatient infusions.

"It would have been helpful if the authors could identify who will benefit from IV lidocaine therapy and who won't, although this could be impossible to achieve, as most of these patients are on so many diverse preventive medications," Narouze noted.

Nevertheless, given the challenges of conducting a large, prospective randomized controlled trial, "we need to count on other available data sources, and the current study by Schwenk's team represents the real-world data," said Narouze.

Also commenting for Medscape Medical News, Jason Ray, MBBS, consultant neurologist in the Department of Neurology at Alfred Hospital and Monash University, Melbourne, Australia, and at Austin Health, Heidelberg, Australia, noted the study provides "valuable evidence of the efficacy and safety of intravenous lidocaine, publishing the largest series to date in the literature detailing the inpatient and 1-month response rates." Ray was not associated with the research.

No study funding was listed. Schwenk has been a consultant, advisory panel member, or received honoraria from AbbVie, Amgen, Aeon BioPharma, Axsome Therapeutics, Curelator, Epalex, GlaxoSmithKline Consumer Health Holdings, electroCore Medical, Impel NeuroPharma, Lilly USA, Medscape, Lundbeck, Nocera, Pulmatrix, Revance, Salvia, Bioelectronics, Satsuma Pharmaceuticals, Teva Pharmaceuticals, Theranica, Thermaquil, and Trillen Medical.

Narouze reports no relevant financial relationships. Ray reports receiving funding from the Pharmaceutical Society of Australia and the Limbic and has been supported by unrestricted funding grants from Viatris and Novartis for educational material. He has also received support from Lundbeck for the running of a trial of eptinezumab vs lidocaine.

BMJ Reg Anesth Pain Med. Published online May 23, 2022. Full text

https://www.medscape.com/viewarticle/975011