A chronopharmacological preventive treatment for sleep-related migraine headaches and chronic morning headaches: Nitric oxide supersensitivity can cause sleep-related headaches in a subset of patients.

Frequent and recurrent migraine headaches can, over time, pose the additional risks of stroke, brain damage, heart failure and attention deficit. This is why prevention should always be a part of the treatment. Nitric oxide supersensitivity is the hypothesis upon which this model is based. Its role in causing migraine headaches and chronic morning headaches can be triggered by both normal and abnormal characteristics of the sleep cycle and more specifically by the release of nitric oxide that occurs towards the end of the sleep cycle. Stress and the age-related loss of sleep continuity, together with the corresponding increase in cortisol levels, potentiate delta rebound. Delta rebound results in deeper sleep intensity. It is associated with increased nitric oxide production. Increased delta rebound then causes an increase in the amount and duration of nitric oxide release at night. Migraineurs are susceptible to migraine headaches because they are supersensitive to nitric oxide. The diurnal pattern of the incidence of sleep-related headaches in a subset of the general population is caused by the effect of nitric oxide supersensitivity during the sleep cycle. The proposed treatment is for both sleep-related migraine headaches and chronic morning headaches. It consists of melatonin and moclobemide taken during the night, close the end of the sleep cycle so as to achieve the maximum concentrations. Both melatonin and moclobemide affect three important aspects of sleep-related headaches: nitric oxide supersensitivity, stress system dysfunction and sleep pathology. Both melatonin and moclobemide have demonstrated effectiveness in preventing migraine headaches. Additionally, both melatonin and moclobemide are compatible with most of the other therapeutic agents used to prevent migraine headaches and with at least 1 therapeutic agent that is used to treat migraine headaches.