CBT Plus Amitriptyline Effective in Treating Chronic Migraine in Youth

tricyclic antidepressant
tricyclic antidepressant
A combination of treatment with CBT and the tricyclic antidepressant amitriptyline led to greater improvements in youth with chronic migraine compared with treatment with headache education and amitriptyline.

In a new study by researchers at the University of Cincinnati College of Medicine, a combination of treatment with cognitive behavioral therapy (CBT) and the tricyclic antidepressant amitriptyline led to greater improvements in youth with chronic migraine compared with treatment with headache education (HE) and amitriptyline.1

Approximately 1.75% of children and adolescents experience chronic migraine.2 The severity of associated functional impairments highlights the pressing need for successful treatments in this group.3 According to the investigators in a previous study, CBT “has been shown to be effective in treating chronic pain among children and adolescents by modifying behavioral responses to pain and using active coping skills, such as relaxation techniques and cognitive strategies.”4

The researchers previously conducted a randomized trial in which they examined the outcomes of CBT plus amitriptyline (n=64) and HE plus amitriptyline (n=71) in youth aged 10 to 17 years.5 In addition to receiving amitriptyline, participants attended 8 individual CBT or HE sessions with a therapist during weeks 1 to 8, followed by 2 booster sessions at weeks 12 and 16, and a post-treatment session at week 20.

Individuals in both groups maintained daily headache diaries in which they indicated medication use; headache occurrence, duration, and intensity; and migraine symptoms. The results showed fewer headache days and reduced disability in the CBT-plus-amitriptyline group vs the HE-plus-amitriptyline group after the 20-week study period. During a 1-year follow-up period, participants received a booster session of CBT or HE every 3 months.

The current study analyzed these earlier observations and compared the trajectory of improvements between the 2 groups over the 20-week period, based on clinically significant benchmarks of a ≥50% decrease in headache frequency and a reduction in headache days to ≤4 per month.

The findings demonstrate that a larger percentage of participants receiving CBT plus amitriptyline  reached a 50% reduction in migraine frequency during each month of treatment compared with HE plus amitriptyline (month 1: 27% vs 10%, P =.014; month 2: 43% vs 20%, P =.004; month 3: 56% vs 33%, P =.009; month 4: 70% vs 48%, P =.012; month 5: 72% vs 44%, P =.002).

In addition, significantly more participants in the CBT-plus-amitriptyline  group reached ≤4 headache days per month for months 3, 4, and 5 compared with those in the HE-plus-amitriptyline  group (month 1: 6% vs 3%, P =.352; month 2: 17% vs 7%; P =.068; month 3: 36% vs 15%, P =.006; month 4: 46% vs 22%, P =.005; month 5: 54% vs 21%, P <.001).

“Results of these analyses indicate that initial decreases in headache frequency began as early as the first month of treatment for both groups and continued to decrease over the course of the treatment phase, with the CBT+A [amitriptyline] group achieving a faster rate of headache day reduction,” the investigators wrote. “These results further support the use of CBT as a frontline treatment for chronic migraine among children and adolescents.”

Summary and Clinical Applicability

CBT plus amitriptyline was found to be more effective in reducing headache frequency than headache education plus amitriptyline. 


The mechanisms underlying the effects of CBT on headache reduction are still unknown and should be explored in future studies.

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  1. Kroner JW, Peugh J, Kashikar-Zuck SM, et al. Trajectory of improvement in children and adolescents with chronic migraine: results from the cognitive behavioral therapy and amitriptyline trial [published online January 17, 2017]. J Pain. pii: S1526-5900(17)30016-0. doi:10.1016/j.jpain.2017.01.002
  2. Lipton RBManack ARicci JAChee ETurkel CC, Winner P. Prevalence and burden of chronic migraine in adolescents: results of the chronic daily headache in adolescents study (C-dAS). Headache. 2011;51(5):693-706. doi:10.1111/j.1526-4610.2011.01885.x
  3. Hershey ADPowers SWBentti ALLeCates S, deGrauw TJ. Characterization of chronic daily headaches in children in a multidisciplinary headache center. Neurology. 2001;56(8):1032-1037.
  4. Eccleston CPalermo TMWilliams AC, et al. Psychological therapies for the management of chronic and recurrent pain in children and adolescents. Cochrane Database Syst Rev. 2014;(5):CD003968. doi:10.1002/14651858.CD003968.pub4
  5. Powers SWKashikar-Zuck SM, Allen JR, et al. Cognitive behavioral therapy plus amitriptyline for chronic migraine in children and adolescents: a randomized clinical trial. JAMA. 2013;310(24):2622-2630. doi:10.1001/jama.2013.282533