Amitriptyline, which is a
noradrenaline reuptake and
5-HT reuptake inhibitor, has an established role in the management of chronic
tension-type headaches. In a single-blind study, patients with chronic
tension-type headache were randomized to either
fluoxetine 20 mg (a selective 5-HT reuptake inhibitor) or
desipramine 75 mg (a selective
noradrenaline reuptake inhibitor) and followed for 12 weeks to compare the effectiveness of the two drugs in improving
headache, and to assess whether
pain control is related to changes in depression. Patients were evaluated at weekly intervals on an analog
pain-rating scale and at 4-weekly intervals on the Montgomery and Asberg Depression Rating Scale (MADRS), the MOS general health status questionnaire (SF36), the Hospital Anxiety and Depression Scale (
HADS), and a side effects checklist. Eighteen patients were randomized to take
fluoxetine and 19 to take
desipramine. Of the 25 patients who completed the trial, 12 were on
fluoxetine and 13 were on
desipramine. There was no significant difference between the two groups at baseline nor in change of
pain; reduction in use of
analgesic medication; nor change in the
HADS, MADRS, or SF36 scores at 12 weeks, but 72% of patients who completed the study improved, and this improvement almost exactly mirrored the improvement on the MADRS. The results from this trial are compatible with the notion that the beneficial effect of
antidepressants in chronic
tension-type headache is indirect, mediated by an effect on depression, and not more,dependent on
serotonin reuptake inhibition than
noradrenaline reuptake inhibition.