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BackgroundHeadache is a common manifestation of post-coronavirus disease (COVID) condition. We aimed to describe the need and effectiveness of acute and preventive medications in a series of 100 consecutive patients evaluated in a headache unit. MethodsObservational descriptive study with a series of cases design. Patients with confirmed COVID diagnosis that were referred due to headache following COVID were included. Patients were evaluated and treated by headache experts. The study included patients infected between March 1, 2020, and January 31, 2022. Demographic variables and clinical information at the moment of the treatment use were gathered. Response to treatment was evaluated according to pain freedom response two hours after the use of the acute medication, and in the case of the preventive medication, the 50%, 30% and 75% responder rates were calculated. ResultsPatients were aged 48.0 (standard deviation (SD): 12.4), were female (84%) and had prior history of headache (56%), anxiety (42%), sleep disorders (37%), and depression (26%). The mean time between the infection and the evaluation was 7.2 (SD: 4.0) months. The most common headache phenotype was holocranial (63%), frontal (48%), pressing (75%), of moderate intensity (7 out of 10), and accompanied by photophobia (58%). Acute medication was required by 93%, being paracetamol (46%) the most frequently used drug, followed by ibuprofen (44%). The drugs with the higher proportion of 2-hour pain-freedom response were dexketoprofen (58.8%), triptans (57.7%), ibuprofen (54.3%) and paracetamol (43.1%).Preventive treatment was required by 75% of patients. The most frequently used drugs were amitriptyline (66%), anesthetic blockades (18%) and onabotulinumtoxinA (11%). The drugs with the higher 50% responder rate were amitriptyline (45.5%), mirtazapine (50%) and anesthetic blockades (38.9%). The higher 75% responder rate was experienced following onabotulinutoxinA (18.2%) and the higher 30% responder rate was obtained following amitriptyline and onabotulinumtoxinA (72.7%). ConclusionsThe majority of patients required acute medication, with triptans and non-steroidal anti-inflammatory drugs being the therapies with the best results. Three quarters of patients required preventive medication. The most frequently used drug was amitriptyline, which obtained the best results. In some treatment-resistant patients, anesthetic blockades and onabotulinumtoxinA were also beneficial.