Cognitive behavioral therapy plus amitriptyline for chronic migraine in children and adolescents: a randomized clinical trial

JAMA. 2013 Dec 25;310(24):2622-30. doi: 10.1001/jama.2013.282533.


Importance: Early, safe, effective, and durable evidence-based interventions for children and adolescents with chronic migraine do not exist.

Objective: To determine the benefits of cognitive behavioral therapy (CBT) when combined with amitriptyline vs headache education plus amitriptyline.

Design, setting, and participants: A randomized clinical trial of 135 youth (79% female) aged 10 to 17 years diagnosed with chronic migraine (≥15 days with headache/month) and a Pediatric Migraine Disability Assessment Score (PedMIDAS) greater than 20 points were assigned to the CBT plus amitriptyline group (n = 64) or the headache education plus amitriptyline group (n = 71). The study was conducted in the Headache Center at Cincinnati Children's Hospital between October 2006 and September 2012; 129 completed 20-week follow-up and 124 completed 12-month follow-up.

Interventions: Ten CBT vs 10 headache education sessions involving equivalent time and therapist attention. Each group received 1 mg/kg/d of amitriptyline and a 20-week end point visit. In addition, follow-up visits were conducted at 3, 6, 9, and 12 months.

Main outcomes and measures: The primary end point was days with headache and the secondary end point was PedMIDAS (disability score range: 0-240 points; 0-10 for little to none, 11-30 for mild, 31-50 for moderate, >50 for severe); both end points were determined at 20 weeks. Durability was examined over the 12-month follow-up period. Clinical significance was measured by a 50% or greater reduction in days with headache and a disability score in the mild to none range (<20 points).

Results: At baseline, there were a mean (SD) of 21 (5) days with headache per 28 days and the mean (SD) PedMIDAS was 68 (32) points. At the 20-week end point, days with headache were reduced by 11.5 for the CBT plus amitriptyline group vs 6.8 for the headache education plus amitriptyline group (difference, 4.7 [95% CI, 1.7-7.7] days; P = .002). The PedMIDAS decreased by 52.7 points for the CBT group vs 38.6 points for the headache education group (difference, 14.1 [95% CI, 3.3-24.9] points; P = .01). In the CBT group, 66% had a 50% or greater reduction in headache days vs 36% in the headache education group (odds ratio, 3.5 [95% CI, 1.7-7.2]; P < .001). At 12-month follow-up, 86% of the CBT group had a 50% or greater reduction in headache days vs 69% of the headache education group; 88% of the CBT group had a PedMIDAS of less than 20 points vs 76% of the headache education group. Measured treatment credibility and integrity was high for both groups.

Conclusions and relevance: Among young persons with chronic migraine, the use of CBT plus amitriptyline resulted in greater reductions in days with headache and migraine-related disability compared with use of headache education plus amitriptyline. These findings support the efficacy of CBT in the treatment of chronic migraine in children and adolescents.

Trial registration: Identifier: NCT00389038.

Publication types

  • Randomized Controlled Trial
  • Research Support, N.I.H., Extramural

MeSH terms

  • Adolescent
  • Amitriptyline / therapeutic use*
  • Antidepressive Agents, Tricyclic / therapeutic use*
  • Child
  • Chronic Disease
  • Cognitive Behavioral Therapy / methods*
  • Combined Modality Therapy
  • Female
  • Headache / drug therapy*
  • Humans
  • Male
  • Migraine Disorders / drug therapy*
  • Patient Education as Topic
  • Treatment Outcome


  • Antidepressive Agents, Tricyclic
  • Amitriptyline

Associated data