Olfaction in migraine and its psychiatric comorbidities: a narrative review

Author:Ciro De Luca, Martina Cafalli, Alessandra Della Vecchia, Sara Gori, Alessandro Tessitore, Marcello Silvestro, Antonio Russo & Filippo Baldacci
Volume Info:Volume 6 January 2021
Article Information

Volume 6 January 2021, pages 38-49
Received: 28th September 2020; Accepted 12th October 2020

Ciro De Luca, Sara Gori & Filippo Baldacci
Neurology Unit, Department of Clinical and Experimental Medicine, University of Pisa, 56126 Pisa, Italy.

Martina Cafalli
Unit of Neurorehabilitation, Department of Medical Specialties, University Hospital of Pisa, 56126 Pisa, Italy

Alessandra Della Vecchia
Unit of Psychiatry, Department of Clinical and Experimental Medicine, University of Pisa, 56126 Pisa, Italy.

Alessandro Tessitore, Marcello Silvestro, Antonio Russo & Filippo Baldacci
Department of Advanced Medical and Surgery Sciences, Headache Center, I Clinic of Neurology and Neurophysiopathology, University of Campania “Luigi Vanvitelli”, Naples, Italy

Author Contributions: Conceptualization, C.D.L., M.C. and F.B.; writing—original draft preparation, C.D.L., M.C.; writing—review and editing, F.B., C.D.L., A.D.V., M.S., A.T. and A.R.; supervision S.G. All authors have read and agreed to the published version of the manuscript.

Conflicts of Interest: C.D.L received honoraria from Lilly and research funding from Novartis. A.T. has received speaker honoraria from Novartis, Schwarz Pharma/UCB, Lundbeck, Abbvie and Glaxo. A.R. has received speaker honoraria from Allergan, Novartis, Lilly and Teva and serves as an associate editor of Frontiers in Neurology (Headache Medicine and Facial Pain session).

Funding: This research received no specific grant from any funding agency in the public, commercial, or not for-profit sectors.


Migraine is a primary headache with a constellation of neurovegetative and sensory-related symptoms, comprehending auditory, visual, somatosensorial and olfactory dysfunctions, in both ictal and interictal phases. Olfactory phenomena in migraine patients consist in ictal osmophobia, interictal olfactory hypersensitivity and an increased sensitivity to olfactory trigger factors. However, osmophobia is not listed as an associated symptom for migraine diagnosis in ICHD-3.

We reviewed the literature about the anatomical circuits and the clinical characteristics of olfactory phenomena in migraine patients, and highlighted also the common comorbidities with psychiatric disorders.

The evidence suggests a potential role of the olfactory dysfunctions as diagnostic, prognostic and risk biomarker of migraine in clinical practice. Olfactory assessment could be useful in reducing the overlap between migraine and other primary headaches – especially the tension type one – or secondary headaches (ictal osmophobia, olfactory trigger factors), and in predicting migraine onset and its chronic transformation (ictal osmophobia). Furthermore, ictal osmophobia and olfactory hypersensitivity showed to be related with an increased risk of psychiatric comorbidities and suicidality, probably beacause of the sharing of anatomical circuits (in particular the limbic system).

In conclusion, the assessment during clinical interviews of olfactory phenomena, with the validation of scales or scores to measure olfactory dysfunctions, surpassing the binary presence/absence paradigm, could improve the diagnostic and prognostic possibilities, especially in tertiary headache centers.


Osmophobia, Olfactory Hypersensivity, Migraine, Psychiatric Disorders, Somatosensory Hypersensitivity



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