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Treatment-Resistant Depression — MRCPsych Paper B MCQ

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HardMood DisordersTreatment-Resistant DepressionMRCPsych Paper B

A 42-year-old man is reviewed in a specialist mental health service for severe unipolar depression. The diagnosis, adherence, physical health and possible comorbid conditions have been reviewed, with no remediable cause of non-response identified. He had no clinically significant response to adequate trials of sertraline and citalopram. He has now taken venlafaxine 225 mg daily for 8 weeks, with a limited but meaningful response and good tolerability. He declines psychological treatment and, after discussion of the increased side-effect burden, wishes to continue venlafaxine and try pharmacological augmentation. Renal and thyroid function, serum calcium and other baseline investigations are satisfactory, and he takes no interacting medication. According to NICE, which is the most appropriate next step?

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Correct answer: E — Augment venlafaxine with lithium

The correct answer is E. NICE includes lithium augmentation among specialist further-line options when antidepressant treatment has produced no or limited response and the person prefers combination pharmacotherapy despite its additional adverse-effect burden. This patient has obtained some benefit from well-tolerated venlafaxine and specifically wishes to retain it, favouring augmentation over switching to mirtazapine or a TCA. Lithium requires baseline renal and thyroid function and calcium assessment, serum-level monitoring and ongoing toxicity surveillance. Sodium valproate is not a recommended augmentation treatment for unipolar depression. Esketamine with an SSRI or SNRI is not recommended by NICE TA854. Importantly, second-generation antipsychotic augmentation would also normally be a NICE-listed option; its presence in the original options made the unrepaired question non-unique.

Reference: National Institute for Health and Care Excellence. Depression in adults: treatment and management (NG222), sections 1.9.8–1.9.9 and 1.4.25–1.4.32. 2022, reviewed 2026. https://www.nice.org.uk/guidance/ng222/chapter/recommendations