Pharmacological Treatment Algorithm for Treatment-Refractory Depression These recommendations are based on the Maudsley Prescribing Guidelines 2018, according to which, depression is treatment refractory when it does not respond to sequential trials of three different antidepressants as recommended in their algorithms. In the first three steps below, we have enlisted the recommended pharmacological treatment options for an episode of depression. subsequently, we list the options for treatment-refractory depression. Maudsley Prescribing Guidelines focus on the pharmacological treatment options and algorithms, never nevertheless, they acknowledge the important role of non-pharmacological interventions in its treatment and recommend considering one of the appropriate options like cognitive behaviour therapy and/or behavioural activation and other factors identified as being responsible for resistance. Step 1: Recommend an SSRI or mirtazapine. monitor for signs and effects for 3- to 4 w