DOI: 10.1002/ejp.2270 ISSN: 1090-3801

Effects of chronic daily headache with subclinical depression on brain volume: A systematic review and meta‐analysis

Chih‐Lung Lin, Hsien‐Yuan Lane, Cheuk‐Kwan Sun, Meng‐Hsiang Chen, Chiao‐Yu Lee, Lin Li, Jia‐Jie Lee, Pin‐Yang Yeh
  • Anesthesiology and Pain Medicine


Background and Objective

The relationship between chronic daily headache (CDH), depression symptoms, and brain volume remains unclear.


To investigate the effects of CDH on brain volume and the impact of depressive symptoms (DSs) as well as the effects of demography and medication overuse, PubMed, Embase, and Web of Science databases were systematically searched using appropriate keyword strings to retrieve observational studies from inception to May 2023.


Two distinct comparisons were made in CDH patients: (1) those with DSs versus their pain‐free counterparts and (2) those without DSs versus pain‐free controls. The first comprised nine studies enrolling 225 CDH patients with DSs and 234 controls. Beck depression inventory, Hamilton depression scale, and Hospital anxiety/depression scale were used to assess DSs, revealing significantly more DSs in CDH patients with DSs compared to their controls (all p < 0.05). Besides, the second analysed four studies involving 117 CDH patients without DSs and 155 comparators. Compared to CDH patients without DSs, those with DSs had a smaller brain volume than controls (p = 0.03). Furthermore, CDH patients with DSs who did not overuse medications showed a smaller right cerebral cortical volume than overusers (p = 0.003). A significant inverse correlation between female prevalence and brain volume (p = 0.02) was revealed using regression analysis.


Pain‐induced persistent depressive symptoms not only incur structural alterations but also encompass affective‐motivational changes, involving medication use and gender‐specific health concerns.


This study highlighted the importance of an integrated CDH treatment, emphasizing psychological interventions for the affective‐motivational component alongside pain management.

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