Fatigue, Depression More Common in Patients with Chronic Migraine

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Fatigue was positively correlated with the frequency, duration, severity, and chronicity of migraine episodes, as well as excessive daytime sleepiness.

The incidence of fatigue and related comorbid disorders are more commonly reported in patients with chronic migraine compared with episodic migraine, according to a study published in the Journal of Neurosciences in Rural Practice.1 Investigators believe these findings underscore the need to address these symptoms when creating a holistic treatment plan.

Migraine is characterized by a multitude of triggers, associated illnesses, and manifestations. Episodic migraine evolves into chronic migraine, a more difficult to manage condition linked to lowered quality of life and increased disability, at a rate of 3 – 14% per year. Chronic migraine also accounts for a substantial portion of headache cases addressed in specialized clinics (40 – 65%) and affects approximately 1.4 – 2.2% of the general population.2

“Fatigue is a common accompaniment of migraine being encountered in around 70% of cases,” wrote a group of Indian investigators. “Chronic fatigue syndrome is characterized by debilitating fatigue and other physical symptoms not relieved by rest. The risk of chronic fatigue syndrome is 1.5 times higher in migraine, while headaches have been reported in up to 59% of cases with chronic fatigue syndrome.”

However, the details of the occurrence and severity of fatigue and chronic fatigue syndrome are underreported.

To explore these factors, 60 adult patients with migraine (30 with episodic migraine and 30 with chronic migraine) were enrolled from the Neurology Outpatient Department, GIPMER, a tertiary referral center in New Delhi, India, between February 2019 to July 2020. The primary objective was to analyze the occurrence and severity of fatigue and chronic fatigue syndrome in this patient population. Other objectives were to understand their relationship with other common comorbidities, such as fibromyalgia, anxiety, and depression.

Headache severity was assessed using the Headache Impact Test-6 (HIT-6) score, while fatigue and other migraine-related symptoms were evaluated using the Fatigue Severity Scale (FSS), the American College of Rheumatology’s diagnostic criteria for fibromyalgia, the Generalized Anxiety Disorder 7-Item Scale, the Chalder Fatigue Scale, the Centers for Disease Control and Prevention’s diagnostic criteria for chronic fatigue syndrome, the Epworth Sleepiness Scale (ESS), and the Hamilton Depression Scale. A comparative analysis assessed patients with migraine with and without fatigue and chronic fatigue syndrome.

Although the demographics between migraine groups were comparable, the 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). Additionally, the 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).

The mean HIT-6 score was significantly higher in patients with chronic migraine compared with episodic migraine. Those in the chronic migraine cohort also had a higher mean FSS score (47.87 vs 37.3, respectively; P = .004), as well as a higher percentage of patients with pathological fatigue (83.3% vs 63.3%, respectively; P = .04). Approximately one-fourth (23.33%) of patients with chronic migraine met the criteria of chronic fatigue syndrome.

Fatigue was positively correlated with the frequency, duration, severity, and chronicity of migraine episodes, as well as excessive daytime sleepiness. Chronic fatigue syndrome was associated with fibromyalgia, depression, and anxiety.

Investigators noted using FSS for evaluating fatigue may have limited the findings, as it is designed to determine fatigue within the last 1-week period as opposed to evaluating it during the different phases and in between migraines. Further, a significant number of patients had psychiatric comorbidities, which influenced fatigue assessment. Another limitation was the possibility of selection bias, as the study was performed in a clinic-based, tertiary center where more severe cases are treated. Lastly, the study lacked a control group as the primary objective was determining the characteristics of migraine with and without fatigue. Larger, population-based studies are necessary for future research.

“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.”


  1. 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
  2. Natoli JL, Manack A, Dean B, Butler Q, Turkel CC, Stovner L, et al. Global prevalence of chronic migraine: A systematic review. Cephalalgia. 2010;30:599-609.