Clinical recommendations and treatment algorithm for treatment-resistant depression in Saudi Arabia: an expert Delphi consensus

Background Major depressive disorder (MDD) is a leading cause of disability worldwide, and a substantial proportion of patients fail to respond adequately to standard antidepressant treatments, resulting in treatment-resistant depression (TRD). TRD is associated with increased morbidity, suicide risk, healthcare utilization, and socioeconomic burden. While international guidelines for TRD management exist, their applicability to Saudi Arabia is limited by differences in healthcare infrastructure, treatment availability, and access to specialized services. In addition, existing national guidance does not incorporate recent advances in TRD treatment. Objectives To establish expert consensus on the definition and management of treatment-resistant depression in Saudi Arabia and to develop a practical, evidence-informed treatment algorithm to guide local clinical practice. Methods A modified Delphi methodology was employed, consisting of three anonymous survey rounds conducted among consultant psychiatrists practicing in Saudi Arabia with expertise in MDD and TRD. Delphi statements were developed based on a review of the literature, international guidelines, and regional clinical experience. Panelists rated their agreement using a 5-point Likert scale. Consensus was predefined as ≥ 75% agreement (“agree” or “strongly agree”). Results Nineteen experts participated in the first two Delphi rounds, with sixteen completing the third round. A total of 15 statements were evaluated. Thirteen statements achieved consensus in the first round, one additional statement achieved consensus in the second round, and one statement did not achieve consensus after three rounds. Consensus recommendations addressed the definition of TRD, diagnostic reassessment to exclude pseudo-resistance, individualized treatment selection, strategies for inadequate response, use of adjunctive pharmacological therapies, intranasal esketamine, neuromodulation approaches, psychological interventions, and measurement-based and collaborative care. A treatment algorithm for TRD was developed based on the consensus outcomes. Conclusions This Delphi consensus provides locally relevant, evidence-based recommendations for the management of treatment-resistant depression in Saudi Arabia. The proposed treatment algorithm offers a practical framework to support standardized, individualized, and measurement-based care, facilitating timely access to adjunctive and specialized treatments for patients with TRD.