Management of patients affected by chronic daily headache (CDH) with medication overuse constitutes one of the most important unresolved problems. The uncertainty regarding the classification and the prophylaxis are a remarkable part of this problem. Objectives are to: (1) to evaluate the efficacy of withdrawal therapy following prophylaxis with topiramate and amitriptyline in a population affected by CDH and medication overuse with follow-up at 1 (T1), 3 (T2) and 6 (T3) months; (2) to identify which group of the Silberstein's CDH classification (1994) may benefit from this protocol. Inclusion criteria are patients with CDH (headache for more >15 days/month for at least 3 consecutive months) and medication overuse according with IHS second edition (8.2 group); exclusion criteria are patients with secondary headache. All patients included in the study were hospitalized for 1 week. Type of overuse: combination of medications, 38%; analgesics, 29%; triptans, 29%; opioids, 2%; ergotamines, 2%. During hospitalization the following protocol was applied: desametasone 4 mg i.v./day for 1 week, diazepam 6 mg/day for 10 days and prophylaxis with amitriptylin plus topiramate. This prophylaxis was protracted for at least 6 months. The dosages assumed ranged for amitriptylin from 10 to 20 mg/day and for topiramate from 50 to 100 mg/day. In the last 4 years 105 patients with CDH (age 24-89 years; f 96; m 9) were admitted to the hospital. The protocol was applied in 52 patients (age, 29-65 years; f 49; m 3). At T1, 89% of the patients did not fall again into medication overuse; at T2, 64%; and at T3,45% of the patients remained free from overuse. According to the Silberstein' proposal at T1, 93% of the subjects was affected by transformed migraine; and 7% by tension-type headache. At T3, all the patients free from overuse were affected by transformed migraine. Our data suggest that the patients affected by CDH and medication overuse benefit from withdrawal therapy performed during hospitalization plus prophylaxis with amitriptyline plus topiramate. This combination seems a good pharmacological solution to reduce the risk of relapse.