What aspects of clinical uncertainty are addressed by published competencies in evidence-based medicine? A scoping review.

Our findings suggested that SGA augmentation showed a robust response benefit supported by trial sequential analysis (TSA), whereas lithium’s apparent benefit in conventional meta-analysis was not supported by TSA and became non-significant after small-study/publication-bias adjustments. T3 augmentation was not associated with a significantly higher response than placebo, and only aripiprazole, quetiapine, brexpiprazole and cariprazine had TSA-supported efficacy among individual SGAs. Clinically, these findings support prioritising SGAs with TSA-confirmed benefits while interpreting lithium augmentation effects cautiously when evidence is drawn mainly from small, older placebo-controlled trials. For research and guidelines, the results highlight the need for larger, contemporary placebo-controlled trials to clarify the efficacy of lithium and less-studied SGAs and to strengthen the evidence base for augmentation decisions. Major depressive disorder (MDD) is a widespread chronic and recurrent condition with an estimated annual prevalence of 6% and a lifetime prevalence of 15%. It is recognised as the leading cause of global disability, imposing substantial social and economic costs. Despite the availability of antidepressant treatment, up to one-third of patients failed to achieve remission after at least two adequate trials of antidepressant therapy. This subgroup is often operationalised as treatment-resistant depression (TRD); however, definitions vary across studies. Individuals with inadequate antidepressant response tend to have greater functional impairment, higher healthcare utilisation and increased psychiatric/medical comorbidity than those who respond to first-line treatment.