title: Cognitive behavioral therapy plus amitriptyline for chronic migraine in children and adolescents: a randomized clinical trial.
abstract: OBJECTIVE
  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.
  
  
  METHODS
  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.
  
  
  METHODS
  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.
  
  
  METHODS
  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
  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.
  
  
  BACKGROUND
  clinicaltrials.gov Identifier: NCT00389038.
authors.affiliation: Division of Behavioral Medicine and Clinical Psychology, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio3Headache Center, Cincinnati Children's Hospital Medical Center4Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, Ohio.
authors.forename: Scott W
authors.initials: SW
authors.lastname: Powers
authors.affiliation: Division of Behavioral Medicine and Clinical Psychology, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio4Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, Ohio.
authors.forename: Susmita M
authors.initials: SM
authors.lastname: Kashikar-Zuck
authors.affiliation: Division of Behavioral Medicine and Clinical Psychology, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio3Headache Center, Cincinnati Children's Hospital Medical Center.
authors.forename: Janelle R
authors.initials: JR
authors.lastname: Allen
authors.affiliation: Division of Neurology, Cincinnati Children's Hospital Medical Center3Headache Center, Cincinnati Children's Hospital Medical Center.
authors.forename: Susan L
authors.initials: SL
authors.lastname: LeCates
authors.affiliation: Division of Behavioral Medicine and Clinical Psychology, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio3Headache Center, Cincinnati Children's Hospital Medical Center4Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, Ohio.
authors.forename: Shalonda K
authors.initials: SK
authors.lastname: Slater
authors.affiliation: Division of Behavioral Medicine and Clinical Psychology, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio.
authors.forename: Marium
authors.initials: M
authors.lastname: Zafar
authors.affiliation: Division of Neurology, Cincinnati Children's Hospital Medical Center3Headache Center, Cincinnati Children's Hospital Medical Center4Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, Ohio.
authors.forename: Marielle A
authors.initials: MA
authors.lastname: Kabbouche
authors.affiliation: Division of Neurology, Cincinnati Children's Hospital Medical Center3Headache Center, Cincinnati Children's Hospital Medical Center4Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, Ohio.
authors.forename: Hope L
authors.initials: HL
authors.lastname: O'Brien
authors.affiliation: Division of Behavioral Medicine and Clinical Psychology, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio4Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, Ohio.
authors.forename: Chad E
authors.initials: CE
authors.lastname: Shenk
authors.affiliation: Division of Behavioral Medicine and Clinical Psychology, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio4Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, Ohio.
authors.forename: Joseph R
authors.initials: JR
authors.lastname: Rausch
authors.affiliation: Division of Neurology, Cincinnati Children's Hospital Medical Center3Headache Center, Cincinnati Children's Hospital Medical Center4Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, Ohio.
authors.forename: Andrew D
authors.initials: AD
authors.lastname: Hershey
mesh_terms: D000293:Adolescent; D000639:Amitriptyline / Q000627:therapeutic use*; D000929:Antidepressive Agents, Tricyclic / Q000627:therapeutic use*; D002648:Child; D002908:Chronic Disease; D015928:Cognitive Behavioral Therapy / Q000379:methods*; D003131:Combined Modality Therapy; D005260:Female; D006261:Headache / Q000188:drug therapy*; D006801:Humans; D008297:Male; D008881:Migraine Disorders / Q000188:drug therapy*; D010353:Patient Education as Topic; D016896:Treatment Outcome
chemical_list: D000929:Antidepressive Agents, Tricyclic; D000639:Amitriptyline