New strategies for the treatment and prevention of primary headache disorders.

The primary headache disorders, which include migraine, cluster headache and tension-type headache, are among the most common diseases and leading causes of disability worldwide. The available treatment options for primary headache disorders have unsatisfactory rates of efficacy, tolerability and patient adherence. In this Review, we discuss promising new approaches for the prevention of primary headache disorders, such as monoclonal antibodies targeting calcitonin gene-related peptide (CGRP) or its receptor, and small-molecule CGRP receptor antagonists. Neuromodulation approaches employing noninvasive or implantable devices also show promise for treating primary headache disorders. Noninvasive treatments, such as transcranial magnetic stimulation and transcutaneous peripheral nerve stimulation, are delivered by devices that patients can self-administer. Implantable devices targeting the occipital nerves, sphenopalatine ganglion or high cervical spinal cord are placed using percutaneous and/or surgical procedures, and are powered either wirelessly or by surgically implanted batteries. These new and emerging treatments have the potential to address unmet patient needs and reduce headache-associated disability.