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Clinical Atlas Prestige · Evidence-first

Psych VivasGeneral adult psychiatry — psychosis

Psych Vivas · General adult psychiatry — psychosis

Treatment-resistant schizophrenia — structured clinical viva

Fellowship viva on established TRS after two adequate trials: TRRIP, clozapine core, InterSePT, LAI context, ultra-TRS and ECT augmentation.

clinical
On this page & tools

Target exams

FRANZCPMRCPsychABPNMD-DNB

Target exams

FRANZCPMRCPsychABPNMD-DNB
Prompt
You are the psychiatry registrar in a community psychosis clinic. A 32-year-old man with schizophrenia has completed two documented adequate antipsychotic trials (risperidone 6 mg for 8 weeks with plasma level in range; olanzapine 20 mg for 8 weeks with verified supervised dosing) with persistent positive symptoms. Bipolar screen is negative; urine drug screen is negative; TSH and B12 are normal. He asks why you are 'pushing the dangerous blood drug', whether shock treatment is next, and whether a 'monthly injection will fix resistance'. Discuss TRRIP definition, clozapine offer with monitoring, InterSePT, LAI role, and ultra-TRS/ECT logic.

Interpretation

Reveal interpretation

This is true TRS by TRRIP-style criteria: two adequate antipsychotic trials failed with adherence reasonably confirmed, pseudo-resistance reasonably excluded. Confirm ongoing risk, residual symptoms, smoking status, and psychosocial package. Measurement-based care continues.[1][6]

Clozapine is the evidence-based next step — Kane established superiority in defined TRS. Consent must cover benefits (unique efficacy; InterSePT suicide signal in high-risk schizophrenia) and risks (neutropenia monitoring, early myocarditis vigilance, constipation/ileus, metabolic effects, seizures, sedation). Monitoring infrastructure is non-negotiable: no bloods, no drug; slow titration; smoking/CYP1A2 education.[2][3][5][6]

LAI is not the primary next step here because adherence was already verified on the failed trials — explain that monthly injections address adherence-related pseudo-resistance, not true pharmacological TRS. LAI remains useful later for other reasons but does not replace clozapine once TRRIP is met.[1][6]

ECT is not automatic next before clozapine; it becomes highly relevant if clozapine later fails adequately (ultra-TRS) — Petrides supports ECT augmentation of clozapine for persistent positives. Discuss consent, cognitive risks, and anaesthetic pathway calmly.[4]

Key points

Two adequate failures change the algorithm

Re-check diagnosis once more, then offer clozapine with real monitoring — do not restart random incomplete SGA cycles.

InterSePT is examiner gold

Clozapine reduces suicidal behaviour versus olanzapine in high-risk schizophrenia/schizoaffective disorder.

Ultra-TRS needs a proven clozapine trial

Dose, duration, plasma level, adherence — then augmentation/ECT.
[1] [2] [3] [4]

References

  1. [1]Howes OD, McCutcheon R, Agid O, et al. Treatment-Resistant Schizophrenia: Treatment Response and Resistance in Psychosis (TRRIP) Working Group Consensus Guidelines on Diagnosis and Terminology Am J Psychiatry, 2017.PMID 27919182
  2. [2]Kane J, Honigfeld G, Singer J, et al. Clozapine for the treatment-resistant schizophrenic. A double-blind comparison with chlorpromazine Arch Gen Psychiatry, 1988.PMID 3046553
  3. [3]Meltzer HY, Alphs L, Green AI, et al. Clozapine treatment for suicidality in schizophrenia: International Suicide Prevention Trial (InterSePT) Arch Gen Psychiatry, 2003.PMID 12511175
  4. [4]Petrides G, Malur C, Braga RJ, et al. Electroconvulsive therapy augmentation in clozapine-resistant schizophrenia: a prospective, randomized study Am J Psychiatry, 2015.PMID 25157964
  5. [5]Galletly C, Castle D, Dark F, et al. Royal Australian and New Zealand College of Psychiatrists clinical practice guidelines for the management of schizophrenia and related disorders Aust N Z J Psychiatry, 2016.PMID 27106681
  6. [6]Kane JM, Agid O, Baldwin ML, et al. Clinical Guidance on the Identification and Management of Treatment-Resistant Schizophrenia J Clin Psychiatry, 2019.PMID 30840788