Objective: The objective of this study was to test the superiority of multidisciplinary approach, that is, Short-Term Psychodynamic Psychotherapy (STPP) plus drug of choice, versus monotherapy, that is, OnabotulinumtoxinA (OnaBoNT-A). Method: We consecutively recorded data from chronic migraine (CM) patients, with or without medication overuse headache (MOH), who underwent STPP or OnaBoNT-A, with a 3-month follow-up schedule. Headache days and analgesics intake were monitored as primary outcome measures. Propensity score matching (PSM) was used to eliminate discrepancies between groups. Discriminant function analysis (DFA) was used to pinpoint predictive factors associated with the clinical response. Results: 96 patients with CM (64% with MOH) were treated with STPP and 54 (59% with MOH) with OnaBoNT-A. At baseline, OnaBoNT-A patients had more failed preventive therapies, more years of illness and chronicity, and were older; STPP patients were more depressed and had a higher HIT-6. Both STPP and OnaBoNT-A patients showed a significant reduction of headache days (STPP: −14 vs. OnaBoNT-A:−14.3) and analgesics intake (STPP: −12,3 vs. OnaBoNT-A −13.5 pills/month), respectively. MOH diminished more in STPP, adherence was higher in OnaBoNT-A. Results were confirmed after PSM balancing of the groups for those variables that resulted as different (but age). Conclusion: OnaBoNT-A monotherapy produced similar results to psychotherapy plus medication, after correcting for baseline differences.

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