Refractory migraine: the role of the physician in assessment and treatment of a problematic disease.

Patients affected by chronic forms of headache are often very difficult to treat. Refractory patients are so defined when adequate trials of specific drugs (for acute or prophylactic treatment) failed both to reduce the burden of disease and to improve headache-related quality of life. An escalating approach is suggested to test different kinds of therapies. All comorbid factors should be addressed. More invasive modalities (such as neurostimulation) or promising approaches such as repetitive transcranial magnetic stimulation (rTMS) could be a future major step as third line therapies.