The way to serotonergic use and abuse in migraine

5-HT is currently indicated to play a role in migraine (M). Previously evidenced 5-HT supersensitivity which characterizes M is insufficient to compensate for a possible deficit in 5-HT bioavailability. Inducing a further up-regulation of 5-HT receptor can yield improvement of M syndrome. Chronic treatments of methysergide and propranolol, drugs exerting antagonist action at 5-HT receptors, induced a significant amelioration in 256M sufferers. On the contrary, chronic treatments of ergotamine and sumatriptan, both provided with a 5-HT1 agonist activity, induced a worsening of M in 134 M sufferers. The M worsening was paralleled by an increase in consumption of analgesic drugs. Discussion concerns the effects of the chronically given 5-HT agonists and antagonists as well as the possible receptor mechanism underlying "craving for serotonin" in severe M. The increase of 5-HT supersensitivity evidenced at the end of M attacks is also discussed and its role in determining the interruption of the attack is here suggested.