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doi: 10.1097/01.NT.0000446550.66560.84
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Stress Plays a Role in Headaches, But Two New Studies Find It Has Different Effects

Rukovets, Olga

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ARTICLE IN BRIEF

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Two new studies focused on stress and headache. One found that higher stress levels increased headache frequency, while the other found that reduction in stress from one day to the next was associated with migraine onset.

What role does stress play in headache frequency? In particular, is the period of high stress a headache trigger, or the period after stress is abated? Two new reports shed some light on these important questions.

The first paper, published in the March 26 online edition of Neurology, analyzed electronic diary entries from migraineurs to see if the time after high stress, or “letdown,” affects headache status. Authors Richard B. Lipton, MD, FAAN; Dawn C. Buse, PhD; and Sheryl R. Haut, MD, of the Albert Einstein College of Medicine in the Bronx, NY; and colleagues found that reduction in stress from one day to the next was associated with migraine onset.

The second report, an early released abstract which will be presented at the AAN Annual Meeting this month, analyzed how perceived stress levels corresponded with headache onset in individuals with migraine or tension-type headache (TTH); the authors found that higher stress levels increased headache frequency.

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Neurology author Dr. Buse, associate professor of neurology at Albert Einstein College of Medicine and director of behavioral medicine at the Montefiore Headache Center in the Bronx, said it is important to understand the link between stress and headache because “trigger management, and particularly stress management, are mainstays of migraine management.” These findings, she added, can create opportunities for headache prevention and reduction.

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THE ‘WEEKEND’ HEADACHE

For the Neurology paper, Dr. Lipton and colleagues examined the relationship between perceptions of stress and relaxation after stress with increased probability of a migraine attack, which is sometimes known as a “weekend” headache.

Migraine patients from a tertiary headache center recorded data multiple times daily into an electronic diary about migraine attack experience and subjective stress for three months. The diary included stress levels with two measures: the Perceived Stress Scale (PSS), and the Self-Reported Stress Scale (SRSS). [For the PSS, the authors used an adapted 4-item version to assess the experience of stress over the day. The SRSS, created for this study, was a single-item question: “Overall, how stressful was today?” to be ranked from 0 (“not at all”) to 10 (“extremely stressful”).]

Seventeen participants, mostly women (16) who were about 44 years old on average, completed at least 30 days of diaries. They experienced about five migraine attacks during this time, or 110 in total. About half of the participants were using prophylactic migraine medication during the study duration, including nortriptyline (an antidepressant) and other psychotropic medications including quetiapine for bipolar disorder and citalopram for depression.

The researchers found that heightened stress levels were not usually associated with migraine onset, but the decline in stress from one evening to the next was associated with increased migraine onset within 6,12, or 18 hours (odds ratio 1.5–1.9; all p-values <0.05) for the PSS. Similar results were reported using the SRSS. “We found that a reduction in stress from one day to the next was associated with a nearly five-fold increased risk of migraine onset within six hours,” said Dr. Lipton.

The time-stamped electronic diaries ensured accurate and timely data and reduced any recall bias, she said. But there were some limitations to their study, the authors said, including the relatively small number of enrollees. Additionally, not all of the variables or questions used had been validated, and most subjects were missing some diary entries and data.

The biology of stress is complex and includes activation of both neuroendocrine and sympathetic mechanisms. “Cortisol rises during times of stress and has an anti-nociceptive effect. If cortisol falls in periods of relaxation after stress that may contribute to the triggering of headache,” lead author Dr. Lipton, co-director of the Montefiore Headache Center and professor of neurology at Albert Einstein College of Medicine, observed. The next steps include combining electronic diary data with measures of stress biology, he said.

The study was supported by an investigator-initiated grant from ENDO Pharmaceuticals in Chadds Ford, PA.

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MORE STRESS, MORE HEADACHES?

In a related study to be presented at the AAN annual meeting this month, Sara H. Schramm, PhD, of the University of Duisburg-Essen in Germany, and colleagues, examined self-reported stress levels and headache frequency using data from the population-based German Headache Consortium Study. The study included 5,159 participants aged 21–71 years who were screened quarterly from 2010–2012 with validated questionnaires.

The authors identified tension-type headache in 31 percent of study participants, migraine in 14 percent, coexisting migraine and TTH in 10.6 percent, and unclassifiable headache in 17.3 percent. To measure stress intensity and its effect on headache frequency, the researchers used a visual analogue scale (VAS), ranging from 0 to 100.

Dr. Schramm and colleagues found that an increase of 10 points on the VAS in stress intensity was associated with a 6.3 percent (95% CI: 4.3-8.3 percent) increase in headache days/month for individuals with TTH, a 4.3 percent (2.4-6.2 percent) increase for those individuals with migraine, and a 4 (1.8-6.3 percent) percent increase in individuals with migraine with coexisting TTH. All results were adjusted for sex, age, acute pain medication intake, drinking, smoking, body mass index, and education.

Overall, Dr. Schramm told Neurology Today, individuals who experience headaches — especially migraines — reported higher levels of stress than those who never reported headache. “Increasing stress resulted in increasing headache frequency for all headache subtypes, which was particularly pronounced in participants with tension-type headache. Women and men reported almost the same mean stress levels,” she said.

One potential limitation here was the possible incorrect classification of headache subtypes, Dr. Schramm said, which was detected once retrospectively. The classifications were based on the International Headache Society criteria.

“Our findings are important to support the tailoring of stress-management approaches in patients with different headaches subtypes. The benefit from psychological interventions for stress might be slightly higher in patients with TTH than in migraine patients,” Dr. Schramm said. She added that there need to be further clinical studies which distinguish between headache subtypes,

The study was supported by the German Federal Ministry of Education and Research.

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EXPERT COMMENTARY

Deborah I. Friedman, MD, MPH, FAAN, professor of neurology & neurotherapeutics and ophthalmology at University of Texas Southwestern Medical Center, who was not involved with either study, said that the Neurology paper had several important strengths, including the use of electronic diaries that decrease reliance on recall, use of structured instruments, recording of menstrual status in women, and a fairly large number of diary days. Still, she said, the study had a relatively small number of participants with relatively high education levels that might affect generalizability, as noted by the authors.

“Participants were selected because they had a feeling of impending migraine, which makes one wonder if they had already realized the association with let-down, or whether the let-down was part of the migraine prodrome,” Dr. Friedman said.

The findings emphasize the utility of keeping a headache diary in order to observe patterns and potential triggers for migraines, she said. “If let-down from stress emerges as a trigger, bio-behavioral interventions may be useful.”

In an editorial accompanying the Neurology study, Peter J. Goadsby, MD, PhD, a neurologist at the University of California-San Francisco, wrote: “I think we can say to patients there is an emerging consensus that the migraine brain is vulnerable to change, such as sleep and stress, and therefore best kept stable. We can say there is good clinical evidence — the new study — and both electrophysiological and imaging evidence, to seek advice, when required, to learn to cope with stress.”

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On the surface, the abstract by Dr. Schramm et al., said Dr. Friedman, may suggest opposite results from the Neurology study. However, on closer inspection, she said, there are reasons why they may have come to that conclusion. Since this is only an abstract, it does not tell the whole story. For example, it is not clear which participants had episodic versus chronic headaches, she noted. Also, “participants were evaluated quarterly and there is no mention of headache diaries,” so it is possible that there may have been recall bias, explained Dr. Friedman, thus the exact “timing of the stress in relationship to the headache is uncertain.”

It is also possible that many of the migraine patients were experiencing let-down headaches as reported in the Neurology paper, she said. Neurology author Dr. Lipton agreed that these two sets of findings — though seemingly contradictory — may indeed be complementary. “These two studies asked very different questions on very different time scales. To map these results more precisely would require studies that combine diary methods with 3 month survey methods.”

“Larger studies may help clarify these important findings; inclusion of factors such as serum cortisol levels may give us greater insight into the process,” said Dr. Friedman.

Importantly, both papers point to the “importance of stress management training and practice for patients with migraine,” Dr. Buse said, such as cognitive behavioral therapy (CBT), biofeedback, and relaxation therapies. These techniques, which are relatively low cost and without side effects, should be considered by headache specialists when designing treatment plans for patients, she said.

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LINK UP FOR MORE INFORMATION:

•. AAN Annual Meeting press release: “Does More Stress Equal More Headaches?” http://bit.ly/1jg7IQv

•. Goadsby PJ. Editorial: Reduction in perceived stress as a migraine trigger. Neurology. 2014; 82:1–2. E-pub 2014: March 26.

•. Lipton RB, Buse DC, Hall CB, et al. Reduction in perceived stress as a migraine trigger: Testing the “let-down headache” hypothesis. Neurology. 2014; 82:1–7. E-pub 2014 March 26.

Wolters Kluwer Health | Lippincott Williams & Wilkins

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