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Fatigue Common in Migraine, More Severe in Chronic vs Episodic Disease

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Individuals with chronic migraine report a significantly greater incidence of fatigue and related comorbid disorders than those with episodic migraine, according to findings of a recent study published in the Journal of Neurosciences in Rural Practice.

Specifically, investigators from India reported that severe fatigue affected 60% of participants with chronic migraine compared with just 20% of those with episodic disease. Further, they identified pathological fatigue among more than 80% affected by chronic migraine vs approximately 60% of those with episodic migraine. Of particular note, nearly one quarter of participants with chronic migraine met the criteria for chronic fatigue syndrome (CFS).

Investigators cite research on the prevalence of migraine-associated fatigue, noting it is observed in approximately 70% of cases. The risk of CFS, “characterized by debilitating fatigue and other physical symptoms not relieved by rest,” is estimated to be 1.5 times higher among persons with migraine, they add. Similarly, data show that headaches may occur in up to 59% of persons diagnosed with CFS.

With their cross-sectional observational study, the team was interested in refining current understanding of the prevalence and severity of both fatigue and CFS in patients with episodic vs chronic migraine—the study’s primary objective. The secondary objectives were to explore the relationship of fatigue with conditions that are often comorbid with migraine, including fibromyalgia, depression, and anxiety.

Migraine-associated fatigue is observed in ~70% of cases. The risk of chronic fatigue syndrome is estimated to be 1.5 times higher among persons with migraine. Similarly, data show that headaches may occur in up to 59% of persons diagnosed with CFS.

Adults aged at least 18 years were recruited from the Neurology Outpatient Department, GIPMER, a tertiary neurology referral center in New Delhi, India, between February 2019 to July 2020. The final cohort numbered 60 participants, 30 each with episodic and chronic migraine. Average age was approximately 31 years, the majority (83%) were women.

Headache severity was assessed using the Headache Impact Test-6 (HIT-6) score; measures of fatigue were evaluated using the Fatigue Severity Scale (FSS), the Chalder Fatigue Scale, and the Centers for Disease Control and Prevention’s diagnostic criteria for chronic fatigue syndrome. Comorbid conditions of interest were assessed using the American College of Rheumatology’s diagnostic criteria for fibromyalgia, the Generalized Anxiety Disorder 7-Item Scale, the Hamilton Depression Scale, and the Epworth Sleepiness Scale (ESS).


Cohort characteristics. Although the demographics between migraine groups were comparable, other factors notably differed, according to the study findings. Mean total duration of migraines was higher in patients with chronic migraine compared with episodic migraine (10.1 ± 7.59 vs 6.97 ± 4.74 years, respectively; P = .06). In addition, mean headache frequency was significantly higher in the chronic migraine cohort compared with the episodic group (23.02 days/month, range 15–30 days vs 7.76 days/month, range: 2–15 days, respectively; P <.001).

Of interest, more than half of participants with episodic migraine (53.3%) had a positive family history of migraine vs 33.3% of those with chronic migraine, although the difference did not reach significance.

Disability, QoL. As had been expected, the authors write, the mean HIT-6 score was significantly higher in patients with chronic migraine ((59.43 ± 6.74) compared with episodic migraine (53.2 ± 8.41) (P = .002).

Fatigue. When researchers compared the 2 groups on measures of fatigue, they found those with chronic migraine had a higher mean FSS score (47.87 vs 37.3, respectively; P = .004). A severe FSS score was recorded in 60% of the chronic vs 20% of the episodic migraineurs (P = .004). The chronic migraine group also had a higher percentage of participants with pathological fatigue (83.3% vs 63.3%, respectively; P = .04). Approximately one-quarter (23.33%) of those with chronic migraine met the criteria for CFS compared with 13.33% of the episodic group (P = .038).

Migraine with/without fatigue. A comparison of migraine with and without fatigue and CFS found that total mean duration of headache disorder was significantly higher among those with fatigue (9.62 ± 6.52 years) versus without fatigue (5.25 ± 5.24 years) (P = .022). The team also found that mean scores for headache severity and mean HIT-6 score were significantly higher among those with vs without fatigue. They reported no significant difference, however, with regard to the presence of fibromyalgia, depression, or anxiety between the groups.

Correlation. The investigators reported a positive correlation between fatigue and frequency, duration, severity, and chronicity of migraine episodes, as well as excessive daytime sleepiness. CFS was associated with fibromyalgia, depression, and anxiety.

Among study limitations, the authors point to the observational design which reduces the ability to generalize findings. They also note limitations of using the FSS for evaluating fatigue, given its designed to determine fatigue within a last 1-week period vs during distinct phases of and in between migraines. Further, assessment of fatigue may have been influenced by the prevalence of psychiatric comorbidities. Selection bias also may have affected findings as participants were recruited from a clinic-based, tertiary center.

“Migraineurs need to be assessed and treated for their headache and associated co-morbid disorders which may account for the poor response to treatment,” investigators concluded. “Awareness of migraine related fatigue will help formulate the optimal treatment strategy in an otherwise chronic disabling disorder that requires not only medical therapy for headache but also targeted management of fatigue and its related comorbidities besides psychosocial intervention and support for best results.”

Source: Kumar H, Dhamija K, Duggal A, Khwaja GA, Roshan S. Fatigue, chronic fatigue syndrome and migraine: Intersecting the lines through a cross-sectional study in patients with episodic and chronic migraine. J Neurosci Rural Pract. 2023;14(3):424-431. doi:10.25259/JNRP_63_2022

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