["Psycho-Oncology, Volume 35, Issue 5, May 2026. ", "\nABSTRACT\n\nBackground\nHead and neck cancer (HNC) survivors have a high burden of depression, yet real‐world antidepressant adherence and the role of patient out‐of‐pocket (OOP) costs in this population remain poorly characterized.\n\n\nMethods\nWe analyzed a retrospective cohort of US adults with HNC and a new antidepressant prescription in Merative MarketScan databases (2016–2023). We measured 180‐day adherence using the medication possession ratio (MPR; adherent if MPR ≥ 80%) and 180‐day persistence as no pharmacy‐claims gap > 15 days. We summarized antidepressant cost‐sharing and used multivariable logistic regression to evaluate associations between index‐fill OOP cost and adherence; Kaplan–Meier and Cox models assessed time to first therapy gap by antidepressant class.\n\n\nResults\nAmong 9267 HNC survivors (median age 61 years; 61% male), 42% were adherent and 80% were persistent over 180 days. Six‐month antidepressant OOP spending was low (median $10; mean $18). Higher index‐fill OOP cost was statistically associated with adherence (adjusted OR 1.02, 95% CI 1.02–1.03), but the magnitude was small over the observed cost range and was not clinically meaningful. Persistence did not differ by single antidepressant class; however, use of multiple antidepressant classes was associated with higher discontinuation risk (HR 2.08, 95% CI 1.84–2.34) relative to SSRI monotherapy.\n\n\nConclusions\nIn this claims‐based cohort of HNC survivors, antidepressant OOP costs were modest and did not appear to be a major barrier to adherence. Adherence remained suboptimal, and discontinuation risk was concentrated among patients receiving multiple antidepressant classes, suggesting the need to focus on nonfinancial and clinical drivers of medication continuity.\n\n"]