The authors conducted a systematic review and used a grading system to classify the articles. Most of the studies received a grade of moderate, all of which were retrospective case control studies and case series. A total of 2602 patients with PFO were included in the study, with prevalence rates of migraine ranging from 16% to 64%. Most studies did not report odds ratios, but those that did had wide confidence intervals. Studies that looked at the prevalence of PFO in migraineurs had similar rates to the control group.

The authors also looked at a total of 20 studies with 1194 migraine patients who underwent PFO closure. Resolution of migraine was reported in 10% to 83%, with improvement in 14% to 83%, no change in 1% to 54%, and worsening in about 4% to 8% of patients. Of the few complications noted, most were atrial fibrillation and inguinal hematoma, with late complications of ischemic attacks or stroke and infective endocarditis also observed. Most of these studies received a low to moderate grade. There have been 3 randomized controlled trials of PFO closure, including the MIST, PRIMA, and PREMIUM trials; however none of these trials reached their primary end point, which included a variation of a decrease in either headache frequency or intensity.

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There are a few theories for the link between PFO and migraine. Some of these include subclinical emboli or higher concentrations of serotonin that bypasses the lungs, which could then activate the trigeminal nerve. This systematic review shows that there is inconsistent evidence between migraine and PFO. There is also poor evidence that closing a PFO leads to decreased migraine frequency or intensity. According to the authors, there is not enough evidence to refer patients for closure of PFO in an attempt to help their migraines.

Impact of depression and anxiety on burden and management of episodic and chronic headaches – a cross-sectional multicentre study in eight Austrian headache centres – Zebenholzer K et al

The final study in my review was a prospective look at the impact of anxiety and depression on headache.3 Depression and anxiety are both significant comorbidities in headache patients and can lead to an additional burden in terms of productivity and health care costs.

The study, published in The Journal of Headache and Pain, included a total of 392 patients of which almost 80% were female. About 60% had episodic headaches and the rest were deemed to have chronic headaches. The rates of depression and anxiety were found to be significantly more elevated in those with chronic headaches (64% vs 40% in episodic headache). All patients with headache reported worse quality of life if they also reported depression and/or anxiety. These patients also reported higher rates of unemployment, did not feel understood by colleagues or employers, and were more likely to lose productive days and avoided speaking to others about their headaches.

The study determined that having comorbid psychiatric issues can lead to an even greater reduced quality of life in those patients with headaches. Patients with depression and/or anxiety also had a higher risk of having chronic headaches or probable medication overuse headaches.

Although some of the findings may seem intuitive, this is a large study that highlights the need for better identification and treatment of psychiatric illnesses that impact headache. Chronic headaches and psychiatric comorbidities have a complex interaction and each impact the other; therefore it is important to approach these patients in a holistic manner with a focus on treating all of their pain and psychiatric conditions.


  1. Patniyot IR, Gelfand AA. Acute Treatment Therapies for Pediatric Migraine: A Qualitative Systematic Review. Headache. 2016;56(1):49-70.
  2. Tariq N, Tepper SJ, Kriegler JS. Patent Foramen Ovale and Migraine: Closing the Debate-A Review. Headache. 2016;56(3):462-78.
  3. Zebenholzer K, Lechner A, Broessner G, et al. Impact of depression and anxiety on burden and management of episodic and chronic headaches – a cross-sectional multicentre study in eight Austrian headache centres. J Headache Pain. 2016;17(1):15.