A double-blind randomized controlled trial of topiramate and amitriptyline either alone or in combination for the prevention of migraine

Clin Neurol Neurosurg. 2008 Dec;110(10):979-84. doi: 10.1016/j.clineuro.2008.05.025. Epub 2008 Jul 11.


Objective: Effectiveness of antidepressants and antiepileptic drugs has already been demonstrated for migraine prophylaxis as monotherapy. In the present study, the efficacy and tolerability of amitriptyline and topiramate combination is examined in the prevention of migraine attacks, in comparison to the monotherapy of each drug.

Methods: A total of 73 patients with migraine headache with or without aura are included in this single-center, double-blind, randomized, and controlled trial. Patients were assigned to receive topiramate alone, amitriptyline alone or a combination of these drugs. Frequency, duration and severity of migraine attacks, accompanied symptoms, depressive state, consumption of medications, side effects and patient satisfaction were evaluated.

Results: All treatments resulted in significant improvements in all efficacy measures (p<0.001 for all comparisons). However, patients receiving combination treatment had higher patient satisfaction compared with other groups both at 8 and 12 weeks (p=0.006 and p<0.001, respectively). Patients receiving amitriptyline and combination treatments had better depression scores compared with the topiramate group. Combination group had fewer side effects with a less amount of amitriptyline consumption.

Conclusion: Amitriptyline and topiramate combination may be beneficial for patients with migraine and comorbid depression, particularly in terms of side effects and associated displeasure due to monotherapy.

Publication types

  • Randomized Controlled Trial

MeSH terms

  • Adult
  • Amitriptyline / adverse effects
  • Amitriptyline / therapeutic use*
  • Anticonvulsants / adverse effects
  • Anticonvulsants / therapeutic use
  • Antidepressive Agents, Tricyclic / adverse effects
  • Antidepressive Agents, Tricyclic / therapeutic use
  • Constipation / chemically induced
  • Disorders of Excessive Somnolence / chemically induced
  • Double-Blind Method
  • Drug Therapy, Combination
  • Female
  • Fructose / adverse effects
  • Fructose / analogs & derivatives*
  • Fructose / therapeutic use
  • Humans
  • Male
  • Middle Aged
  • Migraine Disorders / drug therapy*
  • Migraine Disorders / prevention & control*
  • Patient Satisfaction / statistics & numerical data
  • Time Factors
  • Topiramate
  • Treatment Outcome
  • Weight Gain / drug effects


  • Anticonvulsants
  • Antidepressive Agents, Tricyclic
  • Topiramate
  • Amitriptyline
  • Fructose