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Failure to respond to treatment

Last reviewed dd mmm yyyy. Last edited dd mmm yyyy

Authoring team

30% of patients will fail to respond to adequate dopamine D2 receptor blockade with conventional antipsychotics such as haloperidol.

NICE suggest that (1):

  • if symptoms have not responded adequately to treatment:  
    • review the diagnosis
    • check that there has been adherence to antipsychotic medication, prescribed at an adequate dose and for the correct duration
    • check that psychological treatments have been offered and review engagement with these
      • offer CBT if family intervention has been undertaken; if CBT has been undertaken, suggest family intervention for those in close contact with their family
    • consider other causes of non-response, for example comorbid substance or alcohol misuse, concurrent use of other prescribed medication, or physical illness
    • clozapine should be offered if symptoms have not responded adequately despite sequential use of at least two different antipsychotics, one of which should be a non-clozapine second-generation antipsychotic
      • if symptoms have not responded adequately to an optimised dose of clozapine, review the diagnosis, adherence to treatment, engagement with and use of psychological treatments, other possible causes of non-response and measure therapeutic drug levels before offering a second antipsychotic to augment clozapine
        • second drug should not compound the common side effects of clozapine. An adequate trial of augmentation may need to be up to 8-10 weeks

Notes:

  • clozapine:
    • the first of the new generation antipsychotics
    • thought to block a range of dopamine receptors (D1, D2 and D4) and the serotonin receptor
    • there is a 1% risk of agranulocytosis
    • fewer extra-pyramidal side-effects
    • reduces hospitalisation in resistant schizophrenia

Reference:


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