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Patients with medication overuse headache (MOH) experience decreased quality of life (QoL) and increased psychiatric comorbidity. We performed an observational study in patients with MOH to assess whether QoL (primary outcome parameter), depression, and anxiety (secondary outcome parameters) improve after inpatient withdrawal therapy.Forty-two patients undergoing the usual regimen established for inpatient withdrawal therapy at our department completed a structured questionnaires (the Short Form-36 health survey, Self-Rating Depression Scale, and Self-Rating Anxiety Scale) immediately before inpatient withdrawal. Six months after withdrawal, they were examined again with the same questionnaires.Thirty-two patients (27 female) aged 46.8±9.4 years could be interviewed twice. At baseline, QoL was decreased compared with normative data (z-scores ranging from −1.2 to −2.0). Depression was present in 65.6% and anxiety disorder in 71.9% of the patients. At follow-up, physical QoL (P<0.001) and mental QoL (P=0.019) had improved, but QoL was still impaired (z-scores ranging from −0.3 to −1.3). Depression and anxiety scores had decreased significantly. Poor mental QoL and high scores of depression and anxiety at baseline correlated with frequent headaches at follow-up (P=0.013, P=0.024, and P=0.008, respectively).QoL is impaired in patients with MOH, and many patients are depressed and anxious. Inpatient withdrawal therapy lead to a statistically significant improvement of QoL, depression, and anxiety. Poor baseline mental QoL as well as depression and anxiety are associated with poor outcome in terms of headache frequency.