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Report Details Need for Treatment Guidelines on Comorbid Migraine, Major Depressive Disorder


Treatment guidelines for comorbid depression and migraine are warranted to ensure optimal efficacy and avoid possible pitfalls in psychopharmacotherapy, according to study results.

Treatment guidelines for comorbid depression and migraine are warranted to ensure optimal efficacy and avoid possible pitfalls in psychopharmacotherapy, including serotonin syndrome, according to results of a multicenter study published in the International Journal od Neuropsychopharmacology.

Cross-sectional studies have found major depressive disorder (MDD) and headache disorders, such as migraine, routinely co-occur, while longitudinal studies indicate a reciprocal or bidirectional relationship between the disorders.

“Shared etiologic mechanisms include alterations in serotonergic and dopaminergic pathways that are partly reflected in treatment options for either disease as well as fluctuations in ovarian hormones and a dysregulation of the hypothalamic-pituitary-adrenal axis,” researchers wrote.

To better understand patients who suffer a comorbidity of the disorders, researchers conducted an international, multicenter, noninterventional, cross-sectional trial across 10 sites in Europe. Specifically, investigators hoped to increase knowledge on differences in sociodemographic, clinical, psychopharmacotherapuetic, and response characteristics between individuals with MDD with or without comorbid migraine.

Between November 2012 and February 2016, a total of 1419 patients with MDD representative of those encountered in clinical settings were enrolled in the study. Patients were recruited at both university/academic sites and at non-academic outpatient psychiatric service centers.

Depressive symptom severity was calculated via the Montgomery and Åsberg Depression Rating Scale (MADRS) and the Hamilton Rating Scale for Depression. Treatment response was defined as ≥50% MADRS total score reduction during application of 1 antidepressant agent for ≥4 weeks at an adequate dose, authors wrote, whereas “treatment resistance was defined by treatment failure of ≥2 consecutive adequate trials with antidepressants with or without agents for combination/augmentation.”

Detailed clinical interviews were carried out to gather sociodemographic information and clinical data. In addition, all participants exhibited physician-diagnosed migraine.

A total of 11.1% of 1410 participants exhibited comorbid migraine (95% CI: 9.4% to 12.7%), while the condition was found to be more common among females.

Analyses revealed:

  • Patients with MDD and migraine were significantly younger (mean age [SD] 46.5 years [11.5] vs 50.8 years [14.3], P < .001), heavier (mean weight 73.4 kg [18.2] vs 73.2 kg [16.6], P = .025) and more likely to be female (81.4% vs 65.1%, P < .001) and of other than Caucasian origin (8.3% vs 3.3%, P = .002) than those in the MDD without comorbid migraine group
  • A higher proportion of patients in the MDD with comorbid migraine group consisted of outpatients (77.6% vs 63.9%, P = .001) and suffered from comorbid asthma (10.9% vs 2.5%, P < .001)
  • MDD patients with comorbid migraine exhibited a significantly higher total score of the Sheehan Disability Scale (20.9 [6.4] vs 18.7 [7.6], P < .001) used to measure functional impairment
  • Monotherapy in patients with MDD and comorbid migraine was more likely than in MDD patients without comorbid migraine (50.0% vs 38.4%, P = .005)
  • The distribution of administered first-line antidepressants did not differ significantly between the 2 groups, but first-line antidepressant therapy depicted a trend towards the prescription of agomelatine
  • Augmentation of the ongoing antidepressant pharmacotherapy with at least 1 antipsychotic drug was less often established in MDD patients with comorbid migraine than in those without (16.0% vs 26.8%, P = .004)

Researchers also found quality of life was significantly reduced in MDD patients with comorbid migraine, and this cohort tended to exhibit worse responses to the administered antidepressant therapy.

“Given multiple probable etiologic links, the lack of current guidelines for treating patients with MDD and migraine as comorbid condition is surprising and may even be mirrored in our findings regarding treatment strategies in the patient groups,” authors wrote.

The impact of migraine on treatment response and disability in MDD appears plausible while a reverse effect in terms of worsening migraine by poorly treated depression is also a reasonable assumption.

“Consequently, both diseases need to be sufficiently treated, at best as early as possible in terms of a patient-centered approach as described previously in the literature,” researchers concluded.


Fugger G, Dold M, Bartova L, et al. Clinical correlates and outcome of major depressive disorder and comorbid migraine: a report of the European group for the study of resistant depression. Int J Neuropsychopharmacol. Published online September 4, 2020. doi:10.1093/ijnp/pyaa035

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