Children With Migraine at High Risk of Comorbid Anxiety, Depression

Pauline Anderson

June 29, 2022

Children and adolescents with migraine are about twice as likely to have an anxiety or depressive disorder as those without migraine, results from a new review and meta-analysis suggest.

Dr Serena Orr

"This is compelling, high-level evidence showing there's this established comorbidity between migraine and anxiety and depressive symptoms and disorders in this age group," co-investigator Serena L. Orr, MD, a pediatric neurologist and headache specialist at Alberta Children's Hospital and assistant professor in the Department of Pediatrics, University of Calgary, Canada, told Medscape Medical News.

The results "should compel every clinician who is seeing a child or adolescent with migraine to screen for anxiety and depression and to manage that if it's present. That should be the standard of care with this level of evidence," Orr said.

The findings were presented at the American Headache Society (AHS) Annual Meeting 2022.

Incidence Divergence

Previous studies have suggested that 10% to 20% of children and adolescents will experience migraine at some point before adulthood, with the prevalence increasing after puberty.

While the female-to-male ratio is about 1:1 before puberty, there is a "big divergence in incidence curves" afterward ― with the female-to-male ratio reaching 2–3:1 in adulthood, Orr noted. Experts believe hormones drive this divergence, she said, noting that male adults with migraine have lower testosterone levels than male adults without migraine.

Orr and her colleagues were keen to investigate the relationship between child migraine and anxiety symptoms and disorders, as well as between child migraine and depression symptoms and disorders. They searched the literature for related case-control, cross-sectional, and cohort studies with participants of ages up to 18 years.

The researchers selected 80 studies to include in the review. Most of the studies were carried out in the past 30 to 40 years and were in English and other languages. Both community-based and clinical studies were included.

Of the total, 73 studies reported on the association between the exposures and migraine, and 51 were amenable to quantitative pooling.

Results from a meta-analysis that included 16 studies that compared children and adolescents who had migraine with their healthy peers showed a significant association between migraine and anxiety symptoms (standardized mean difference [SMD], 1.13; 95% CI, 0.64 – 1.63; P < .0001).

Compared with children who did not have migraine, those with migraine had almost twice the odds of an anxiety disorder in 15 studies (odds ratio [OR], 1.93; 95% CI, 1.49 – 2.50; P < .0001).

In addition, there was an association between migraine and depressive symptoms in 17 relevant studies (SMD, 0.67; 95% CI, 0.46 – 0.87; P < .0001). Participants with vs without migraine also had higher odds of depressive disorders in 18 studies (OR, 2.01; 95% CI, 1.46 – 2.78; P < .0001).

Effect sizes were similar between community-based and clinic studies. Orr said it is important to note that the analysis wasn't restricted to studies with "just kids with really high disease burden who are going to naturally be more predisposed to psychiatric comorbidity."

"Shocking" Lack of Research

The researchers were also interested in determining whether having migraine along with anxiety or depression symptoms or disorders could affect headache-specific outcomes and whether such patients' conditions would be more refractory to treatment. However, these outcomes were "all over the place" in the 18 relevant studies, Orr reported.

"Some looked at headache frequency, some at disability, some at school functioning; so, we were not able to put them into a meta-analysis," she said.

Only two studies examined whether anxiety or depression earlier in childhood predisposes to subsequent migraine, and so that issue is still unresolved, Orr added.

The investigators also assessed whether outcomes with migraine are similar to those with other headache types, such as tension-type headaches. "We did not find a difference at the symptom or disorder level, but there were fewer of those studies" ― and these, too, were heterogeneous, said Orr.

The researchers did not find any studies of the association between migraine and trauma, which Orr said was "shocking."

"In the broader pediatric chronic-pain literature, there's research showing that having a trauma or stress-related disorder is associated with more chronic pain and worse chronic pain outcomes, but we could not find a study that specifically looked at that question in migraine," she added.

Emerging evidence suggests there may be a bidirectional relationship between migraine and anxiety/depression, at least in adults. Orr said having these symptoms appears to raise the risk for migraine, but whether that's environmental or driven by shared genetics isn't clear.

Experiencing chronic pain may also predispose individuals to anxiety and depression, "but we need more studies on this."

In addition to screening children with migraine for anxiety and depression, clinicians should advocate for better access to mental health resources for patients with these comorbidities, Orr noted.

She added that a limitation of the review was that 82.5% of the studies reported unadjusted associations and that 26.3% of the studies were of low quality.

High-Level Evidence

Commenting for Medscape Medical News, Sara Pavitt, MD, chief of the Pediatric Headache Program and assistant professor in the Department of Neurology, the University of Texas at Austin, said the investigators "should be applauded" for providing "high-level evidence" to better understand the relationship between migraine and anxiety and depression in pediatric patients.

Such information has been "lacking" for this patient population, said Pavitt, who was not involved with the research.

She noted that screening kids for mood disorders is challenging, given the relatively few pediatric mental health care providers. A referral for a psychiatric follow-up can mean a 9- to 12-month wait ― or even longer for children who do not have insurance or use Medicare.

"Providers need to have more incentives to care for patients with Medicare or lack of insurance ― these patients are often excluded from practices because reimbursement is so poor," Pavitt said.

Additional pediatric studies are needed to understand how other mental health disorders, such as panic disorder, phobias, and posttraumatic stress disorder, may be related to migraine, she added.

The study received no outside funding. Orr has received grants from the Canadian Institutes of Health Research and royalties from Cambridge University Press for book publication, and she is on editorial boards of Headache, Neurology, and the American Migraine Foundation. Pavitt serves on an advisory board for Theranica, which produces a neuromodulation device for acute migraine treatment, although this is not directly relevant to this review.

American Headache Society (AHS) Annual Meeting 2022: Abstract OR-19. Presented June 11, 2022.

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