Failure to respond to treatment

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:

• 1. NICE (March 2009). Schizophrenia Core interventions in the treatment and management of schizophrenia in adults in primary and secondary care