Intravenous Lidocaine and Mexiletine in the Management of Trigeminal Autonomic Cephalalgias

Abstract

Lidocaine and mexiletine are class 1B antiarrhythmic drugs that act on sodium channels. Lidocaine is also an important anesthetic and topical agent that is useful in the treatment of multiple pain disorders, and mexiletine is commonly used for neuropathic pain and myotonia. Both intravenous lidocaine and mexiletine are increasingly used to treat pain syndromes and appear to be particularly effective in neuropathic pain. This suggests a role for these agents in patients with headache disorders. This article describes the role of intravenous lidocaine and mexiletine in the management of headache and trigeminal autonomic cephalalgias based on the published literature to date and provides practical guidelines for their use.

SUN: Short‐Lasting Unilateral Neuralgiform Headache Attacks

“…47 The sodium channel blocker mexiletine can be given orally to patients with somatic pain who respond to intravenous lidocaine, and has also demonstrated effectiveness in SUN and other headache syndromes. 48 However, mexiletine is of limited use due to poor tolerability. 38…”

“…Further medications have been used, either alone or in combination, such as clomiphene up to 75 mg daily in one patient, and verapamil up to 960 mg daily in one patient . The sodium channel blocker mexiletine can be given orally to patients with somatic pain who respond to intravenous lidocaine, and has also demonstrated effectiveness in SUN and other headache syndromes . However, mexiletine is of limited use due to poor tolerability …”

Trigeminal Autonomic Cephalalgias: Beyond the Conventional Treatments

“…Matharu et al [77] reported a series of four intractable patients rendered pain free by the infusion. The use of lidocaine and mexiletine, both antiarrthmyic drugs acting on sodium channels, are reviewed in a paper by Marmura [78]. …”

Mexiletine as a treatment for primary erythromelalgia: normalization of biophysical properties of mutant L858F NaV1.7 sodium channels

“…More recently, it has also been found to be effective in several animal models of chronic pain and it has been suggested as a third-line treatment instead of systemic lidocaine for neuropathic pain syndromes (Jarvis and Coukell, 1998; Kuhnert et al ., 1999; Mao and Chen, 2000; Challapalli et al ., 2005; Tremont-Lukats et al ., 2005; Ebell, 2006; Marmura, 2010). Based on its almost complete absorption after oral administration, its low first-pass effect and a plasma elimination half-life of approximately 10–14 h, it is also an orally available alternative to lidocaine for systemic treatment (Middleton, 1980).…”

“…The non-selective sodium channel inhibitor mexiletine hydrochloride [1-methyl-2-(2,6-xylyloxy)ethylamine hydrochloride] has been extensively studied and used clinically for decades because of its antiarrhythmic effects (Chew et al, 1979;Woosley et al, 1984;Fenster and Comess, 1986;Monk and Brogden, 1990). More recently, it has also been found to be effective in several animal models of chronic pain and it has been suggested as a third-line treatment instead of systemic lidocaine for neuropathic pain syndromes (Jarvis and Coukell, 1998;Kuhnert et al, 1999;Mao and Chen, 2000;Challapalli et al, 2005;Tremont-Lukats et al, 2005;Ebell, 2006;Marmura, 2010). Based on its almost complete absorption after oral administration, its low first-pass effect and a plasma elimination half-life of approximately 10-14 h, it is also an orally available alternative to lidocaine for systemic treatment (Middleton, 1980).…”