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Antidepressants are often used in the prophylaxis of chronic headaches, but their effectiveness is uncertain. A recent meta-analysis showed that antidepressants are effective in the treatment of chronic headaches. Double-blind, placebo-controlled studies showed that amitriptyline and fluoxetine may be useful in the prophylaxis of chronic headaches. Further studies are needed in order to evaluate whether there are differences in efficacy among the classes of agents and whether this effect is independent of depression treatment.

Antidepressants in the treatment of chronic headaches: therapy of psychiatric comorbidity or other mechanisms?