When Clozapine Doesn’t Work – Quick Look

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  • Treating schizophrenia can be challenging
  • The last resort medication, clozapine, doesn’t always work.
  • New study from the Treatment Response and Resistance in Psychosis Working Group on next steps for clozapine failure, or “clozapine-resistant schizophrenia”.
  • #1 – Try a higher dose of clozapine for at least three months. Track clozapine with blood levels.
  • #2 – Keeping the dose of clozapine the same, add either amisulpride or oral aripiprazole.
  • #3 – Keeping the dose of clozapine the same, add a 12 session course of ECT (electroconvulsive therapy).
  • #4 – Keeping the dose of clozapine the same, start a course of at least 15 sessions of Cognitive-Behavioral Therapy.
  • #5 – Keeping the dose of clozapine the same, try adding a set of psychosocial interventions.
  • #6 – Keeping the dose of clozapine the same, add a course of Repetitive Transcranial Magnetic Stimulation (rTMS) treatments.
  • If none of the above work it is time to give up on the clozapine, taper it down to a lower dose and then discontinue it, and try using other medications or treatments.
  • Other suggestions about what to do when clozapine doesn’t work probably have little merit at this time.

See our page When Even Clozapine Doesn’t Work in Schizophrenia for the full report.

Elias Wagner, John M Kane, Christoph U Correl, Oliver Howes, Dan Siskind, William G Honer, Jimmy Lee, Peter Falkai, Thomas Schneider-Axmann, Alkomiet Hasan; TRRIP Working Group. Clozapine Combination and Augmentation Strategies in Patients With Schizophrenia —Recommendations From an International Expert Survey Among the Treatment Response and Resistance in Psychosis (TRRIP) Working Group. Schizophrenia Bulletin Vol. 46 No. 6, Dec 1 2020, pp. 1459 – 1470.