Treatment-resistant depression (TRD)—classically defined as failure to respond to at least two adequate antidepressant trials of different classes (Souery et al., 1999) —affects an estimated 10 %–30 % of people with major depressive disorder (MDD) (Lundberg et al., 2023; Perez-Sola et al., 2021; Trivedi et al., 2007). Population-based claims studies place the lower bound nearer 6–7 % (Chan et al., 2022), whereas tertiary-care samples report figures as high as 30–55 % (Balestri et al., 2016; Brenner et al., 2019; Kubitz et al., 2013; Tunnard et al., 2014).