New migraine preventive options: an update with pathophysiological considerations

Abstract

BACKGROUND: The pharmacological treatment of migraine may be acute or preventive. Frequent, severe and long-lasting migraine attacks require prophylaxis. Multiple threads of research over the last 15 years have led to the concept that migraine is generated from a hyperexcitable brain. A variety of causes for hyperexcitability of the brain in migraine have been suggested. These causes include low cerebral magnesium levels, mitochondrial abnormalities, dysfunctions related to increased nitric oxide or the existence of a P/Q type calcium channelopathy. The better knowledge about migraine pathophisiology led us to discuss new treatment options. OBJECTIVES: The aim of the present study is to present an evidence-based review of some new drugs or some agents that even though available for a long time, are not frequently used. METHODS/RESULTS: We present a review of anticonvulsants with various mechanisms of action such as lamotrigine, gabapentin, topiramate, tiagabine, levetiracetam and zonisamide. We also review natural products, like riboflavin and magnesium, botulinum toxin A, a specific CGRP antagonist and the anti-asthma medication montelukast, with pathophysiological discussion. CONCLUSIONS: We aimed to present an update of newer or less frequently used preventive migraine therapies, drugs that might reduce the burden and the costs of a disease that should be considered as a public health problem all around the world.

Effect of serotonergic antidepressant therapy on temperament and character scales in patients with chronic tension‐type headache

“…In a recent study, hyposerotonergic status and increased NO synthetase activity have been found in CTTH patients, thus suggesting a contributory role in the central sensitization of CTTH patients 58 . The efficacy of some drugs used in the treatment of CTTH, such as amitriptyline and SSRI, which is thought to inhibit the presynaptic re‐uptake of 5‐HT, also indicates the involvement of the serotonergic system in the pathophysiology of CTTH 59–62 …”

Increased susceptibility to cortical spreading depression in an animal model of medication-overuse headache

“…Patients with migraine complicated by MOH demonstrate a higher prevalence of cutaneous allodynia (CA) than patients with episodic migraine (15–17). We previously showed that rats develop CA during sustained or intermittent triptan exposure (18,19).…”

Antiepileptic drugs and migraine

“…There is limited information, largely from open label clinical trials, suggesting that zonisamide may be effective in migraine prophylaxis in adults and children (Smith, 2001;Krusz, 2001b;Bigal et al, 2002;Drake et al, 2004;Pakalnis and Kring, 2006;Ashkenazi et al, 2006). Taken together with the available base of information on zonisamide, a case can be made that further study of the drug in controlled trials is warranted.…”