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

Abstract

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: clinicaltrials.gov Identifier: NCT00389038.

Figure 1. Flow of Participants Through the Trial

Figure 2. Results From Baseline to 12-Month Posttreatment Follow-up for Cognitive Behavioral Therapy Plus Amitriptyline (Treatment Group) and Headache Education Plus Amitriptyline (Control Group)

Error bars indicate 95% confidence intervals. The results of the pretest to posttest analyses appear in Table 3. Post hoc longitudinal analyses from posttest to follow-up were also conducted to examine change in the effect of treatment during this period. These analyses were considered post hoc because we did not have any prior expectations with respect to the pattern of results; thus, these analyses were entirely exploratory. For these analyses, PROC MIXED was used to analyze continuous outcomes with random effects for intercepts and slopes over time, whereas PROC GENMOD with a logistic link function was used to analyze longitudinal change in dichotomous outcomes. The first step in each of these analyses was to test an effect for group differences in linear change across the follow-up period. These results suggest that the treatment effects found from baseline to 20-week posttest were maintained throughout the 12-month follow-up period.