Janelle R. Allen

Cognitive Behavioral Therapy Plus Amitriptyline for Chronic Migraine in Children and Adolescents A Randomized Clinical Trial

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 Childrens 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.

Quality of life and emotional functioning in youth with chronic migraine and juvenile fibromyalgia.

Summary:Chronic pain in children is associated with significant negative impact on social, emotional, and school functioning. Previous studies on the impact of pain on children’s functioning have primarily used mixed samples of pain conditions or single pain conditions (eg, headache and abdominal pain) with relatively small sample sizes. As a result, the similarities and differences in the impact of pain in subgroups of children with chronic pain have not been closely examined. Objective:To compare pain characteristics, quality of life, and emotional functioning among youth with pediatric chronic migraine (CM) and juvenile fibromyalgia (JFM). Methods:We combined data obtained during screening of patients for 2 relatively large intervention studies of youth (age range, 10 to 18 y) with CM (N=153) and JFM (N=151). Measures of pain intensity, quality of life (Pediatric Quality of Life; PedsQL, child and parent-proxy), depressive symptoms (Children’s Depression Inventory), and anxiety symptoms (Adolescent Symptom Inventory-4—Anxiety subscale) were completed by youth and their parent. A multivariate analysis of covariance controlling for effects of age and sex was performed to examine differences in quality of life and emotional functioning between the CM and JFM groups. Results:Youth with JFM had significantly higher anxiety and depressive symptoms, and lower quality of life in all domains. Among children with CM, overall functioning was higher but school functioning was a specific area of concern. Discussion:Results indicate important differences in subgroups of pediatric pain patients and point to the need for more intensive multidisciplinary intervention for JFM patients.

Psychiatric comorbidity in pediatric chronic daily headache

Objectives: The objectives of this study were to assess comorbid psychiatric diagnoses in youth with chronic daily headache (CDH) and to examine relationships between psychiatric status and CDH symptom severity, as well as headache-related disability. Methods: Standardized psychiatric interviews (Kiddie Schedule for Affective Disorders and Schizophrenia, KSADS) were conducted with 169 youth ages 10–17 diagnosed with CDH. Participants provided prospective reports of headache frequency with a daily headache diary and completed measures of symptom severity, headache-related disability (PedMIDAS) and quality of life (PedsQL). Results: Results showed that 29.6% of CDH patients met criteria for at least one current psychiatric diagnosis, and 34.9% met criteria for at least one lifetime psychiatric diagnosis. No significant relationship between psychiatric status and headache frequency, duration, or severity was found. However, children with at least one lifetime psychiatric diagnosis had greater functional disability and poorer quality of life than those without a psychiatric diagnosis. Discussion: Contrary to research in adults with chronic headaches, most youth with CDH did not appear to be at an elevated risk for comorbid psychiatric diagnosis. However, patients with a comorbid psychiatric diagnosis were found to have higher levels of headache-related disability and poorer quality of life. Implications for treatment are discussed.

Cognitive Behavioral Therapy plus Amitriptyline for Children and Adolescents with Chronic Migraine Reduces Headache Days to ≤4 Per Month

The objective of this secondary analysis of results from a previously published trial (Clinical Trials Registration Number: NCT00389038) in chronic migraine in children and adolescents was to examine if participants who received cognitive behavioral therapy and amitriptyline reached a greater level of reduction in headache frequency that no longer indicated a recommendation for preventive treatment as compared to those who received headache education and amitriptyline.

Childhood Abuse in Pediatric Patients With Chronic Daily Headache

Recent studies have raised significant concern about the high prevalence of childhood abuse in adults with chronic daily headache (CDH). In a survey of 1348 adult migraine patients,1 it was found that 21% of patients reported a history of childhood physical abuse and 25% reported a history of sexual abuse. Data from the ACE (Adverse Childhood Experiences) study and other studies have also found that childhood physical abuse and other forms of maltreatment were significantly associated with migraine headache.2–4 Although retrospective studies seem to provide strong evidence for an association between childhood abuse and CDH, one prospective longitudinal study did not find a difference between those with and without a documented history of childhood abuse in terms of their risk for chronic pain in adulthood.2 These inconsistent results may be a result of varying methodologies, the effects of recall bias or because the connection between childhood abuse and pain in adulthood may be more complex. More prospective research is needed to investigate the connection between childhood abuse and CDH. Children with CDH form a significant proportion of patients seen in pediatric neurology clinics, accounting for up to one third of newly referred patients.5 There is little research examining the prevalence of childhood physical and sexual abuse in pediatric headache patients, and the impact of an early abuse history in terms of clinical presentation of pediatric CDH patients (headache frequency, severity, disability, and quality of life) is not known. As part of the screening process for a large treatment study for pediatric CDH, our research team gathered comprehensive clinical data, including data on exposure to trauma among the patients. The objectives of this investigation were to 1) specifically examine the prevalence of physical and sexual abuse in these clinically referred children and adolescents with CDH and 2) to compare headache characteristics, headache-related disability, depressive symptoms, and quality of life between those who reported a history of abuse and those who did not. Based on the adult literature, we hypothesized that we would find a higher rate of childhood abuse in CDH than in the general population and a rate similar to what has been reported in the adult literature (ie, approximately 20%). Also, we hypothesized that CDH patients with a positive history of abuse would have higher levels of headache-related disability, more depressive symptoms, and lower quality of life than those without a history of abuse.

Adherence to Biobehavioral Recommendations in Pediatric Migraine as Measured by Electronic Monitoring: The Adherence in Migraine (AIM) Study

The purpose of this investigation was to examine treatment adherence to medication and lifestyle recommendations among pediatric migraine patients using electronic monitoring systems.

Neuromagnetic Abnormality of Motor Cortical Activation and Phases of Headache Attacks in Childhood Migraine

The cerebral cortex serves a primary role in the pathogenesis of migraine. This aberrant brain activation in migraine can be noninvasively detected with magnetoencephalography (MEG). The objective of this study was to investigate the differences in motor cortical activation between attacks (ictal) and pain free intervals (interictal) in children and adolescents with migraine using both low- and high-frequency neuromagnetic signals. Thirty subjects with an acute migraine and 30 subjects with a history of migraine, while pain free, were compared to age- and gender-matched controls using MEG. Motor cortical activation was elicited by a standardized, validated finger-tapping task. Low-frequency brain activation (1∼50 Hz) was analyzed with waveform measurements and high-frequency oscillations (65–150 Hz) were analyzed with wavelet-based beamforming. MEG waveforms showed that the ictal latency of low-frequency brain activation was significantly delayed as compared with controls, while the interictal latency of brain activation was similar to that of controls. The ictal amplitude of low-frequency brain activation was significantly increased as compared with controls, while the interictal amplitude of brain activation was similar to that of controls. The ictal source power of high-frequency oscillations was significantly stronger than that of the controls, while the interictal source power of high-frequency oscillations was significantly weaker than that of controls. The results suggest that aberrant low-frequency brain activation in migraine during a headache attack returned to normal interictally. However, high-frequency oscillations changed from ictal hyper-activation to interictal hypo-activation. Noninvasive assessment of cortical abnormality in migraine with MEG opens a new window for developing novel therapeutic strategies for childhood migraine by maintaining a balanced cortical excitability.

Treatment Adherence in Child and Adolescent Chronic Migraine Patients: Results from the Cognitive Behavioral Therapy and Amitriptyline Trial.

Objectives: To examine treatment adherence among children and adolescents with chronic migraine who volunteered to be in a clinical trial using 3 measures: treatment session attendance, therapy homework completion, and preventive medication use by daily diary. Materials and Methods: Analyses are secondary from a trial of 135 youth aged 10 to 17 years diagnosed with chronic migraine and with a Pediatric Migraine Disability Score over 20. Participants were randomly assigned to cognitive-behavioral therapy plus amitriptyline (CBT+A, N=64) or headache education plus amitriptyline (HE+A, N=71). Therapists recorded session attendance. Completion of homework/practice between sessions was reported to therapists by patients. Patients reported preventive medication adherence using a daily headache diary. Results: Mean session attendance adherence out of 10 treatment sessions was 95% for CBT+A and 99% for HE+A. CBT+A participants reported completing a mean of 90% of home practice of CBT skills between the 10 sessions. Participants reported taking amitriptyline daily at a mean level of 90% when missing diaries were excluded and 79% when missing diaries were considered as missed doses of medication. Discussion: Our findings demonstrate that youth with chronic migraine who agree to be a part of a clinical trial do quite well at attending therapy sessions, and report that they are adherent to completing home/practice between sessions and taking medication. These results lend further support to consideration of CBT+A as a first-line treatment for youth with chronic migraine and suggest that measurement of adherence when this treatment is provided in practice will be important.