Multi-center randomized control trial of etizolam plus NSAID combination for tension-type headache.

OBJECTIVE Benzodiazepines are commonly used for the treatment of tension-type headache (TTH), however, there are few randomized controlled trials recommending the use of these drugs in Japan. This study was undertaken to evaluate the efficacy of etizolam, a thienodiazepine derivative, in combination with a non-steroidal anti-inflammatory drug (NSAID) as an acute treatment for TTH. METHODS The study design was a multi-center randomized control trial and included 144 patients. The diagnosis of TTH was based on the criteria of the International Classification of Headache Disorders-1 and all patients were diagnosed with episodic tension-type headache (ETTH). Changes in the severity of headache and shoulder pain were graded using a Visual Analogue Scale (VAS) before and after administration of drugs. Patients were randomized into NSAID alone (NSAID, mefenamic acid, 250 mg) group and NSAID (mefenamic acid, 250 mg) plus etizolam (0.5 mg) (NSAID-ET) group prior to treatment. RESULTS Although both groups showed a significant drop in VAS for headache and shoulder pain (p<0.01), there was no overall significant difference between the NSAID-ET and NSAID groups. However, headache was improved significantly in female patients (p<0.05), and shoulder pain was improved in young and female patients (p<0.05, p<0.04) in the NSAID-ET group. CONCLUSION This study indicates that the combination treatment of etizolam and NSAID is useful in young or female patients.