Combinations of TCAs, particularly amitriptyline with beta blockers, is a very practical way of treating patients with frequent headache, particularly those associated with depression, stress, anxiety, and sleep problems. In one trial, fluoxetine was not found to be more effective than placebo for migraine prophylaxis. The same study reported that fluoxetine is useful in the treatment of chronic daily headache. However, SSRIs are extensively used in patients with chronic migraine, particularly because of co-morbid depression. In a recent study, S-fluoxetine was found to produce statistically significant improvement of attack frequency, headache days per month, and patients' global impression of its usefulness.
Studies are in progress.
In migraineurs, it is possible that there is disinhibition due to decreased GABAergic inhibition that results in central neuronal hyperexcitability. This situation is similar to that one might see in epilepsy. GABA is highly concentrated in the visual cortex and peri-aqueductal area of the brain stem. A receptor subunits are expressed in cerebral blood vessels. The peripheral effects include reduction of experimental neurogenic inflammation in the trigeminal vascular system, an effect mediated through GABA A receptor agonism.