Chronic tension type headache (CTTH) has a strong impact on the Quality Of Life (QOL). We carried out an open-label randomized clinical trial on 18 patients with CTTH in order to compare two different regimens of pharmacological prophylaxis: the first provided for the use of amitriptyline 20 mg/d during 3 months, while in the second we combined amitriptyline with tizanidine (4 mg/d) in the first 3 weeks of treatment. Our hypothesis is that the combination therapy may guarantee an improvement of QOL even in the early stages of treatment. In fact, it's as well-known, there is a delay of 2-3 weeks in the prophylactic effect of amitriptyline, with a consequent persistence, in the first phases of therapy, of the headache and its negative impact. We assessed the following outcome measures: frequency, pain intensity, duration of headache and the Headache Impact Test (HIT) score, used as headache-related QOL measure. The combination therapy was effective since the first month of treatment, with a significant reduction of the headache, greater than one obtained with amitriptyline alone, in terms of frequency (-52.3% vs. -40.7%), intensity (-59.51% vs. -20.39%) and duration (-53.17% vs. -36.16%). This trend was confirmed by the HIT. Our data suggest that the combination of tizanidine with amitriptyline is faster than the amitriptyline alone in providing an improvement in the headache pattern and correlated QOL.