Migraine with aura (MwA) sufferers, at times, need specific treatments. This is the case when the auras are frequent, prolonged and cause anxiety and distress. Abnormal release of glutamate, which may trigger auras, and abnormal platelet behaviour, which constitutes a possible predisposing factor to MwA, are possible targets for MwA-specific prophylactic therapy. Here we present results obtained using lamotrigine (two open trials), an agent known to inhibit glutamate release, and picotamide, an antiplatelet drug, in the prophylactic treatment of MwA sufferers. Lamotrigine significantly reduced the frequency of MwA attacks, and picotamide together with lamotrigine reduced the duration and/or the occurrence of auras. In comparison to lamotrigine, the therapy with picotamide may have some advantages such as the use of the therapeutic dose from the first day of treatment (lamotrigine needs one month or more to reach such a dose) and the possibility to prevent cerebral ischaemic events and migraine stroke, a rare but severe complication of MwA attacks.