Treatment-resistant schizophrenia
Up to 40% of patients with schizophrenia experience residual symptoms even when clinically stable and adherent with optimal antipsychotic therapy. If residual symptoms are experienced, look for reasons for treatment resistance—see Key questions to assess nonresponse to an antipsychotic.
A patient is considered to have treatment-resistant schizophrenia if they meet all the following criteria1:
- moderate or severe positive, negative or cognitive symptoms of psychosis for 12 weeks or longer
- moderate or severe functional impairment
- monotherapy with 2 antipsychotics given at adequate doses (ie a dose equivalent to 600 mg per day of chlorpromazine) for at least 6 weeks each
- adherent to antipsychotic therapy—ie taken at least 80% of the time, as demonstrated by 2 sources (eg pill counts, checking antipsychotic blood concentration23); ideally, a long-acting injectable antipsychotic should be used for at least 4 months to confirm adherence and achieve steady-state antipsychotic concentration.
If a patient has treatment-resistant schizophrenia, refer to a psychiatrist for review; clozapine may be indicated. If a patient has persistent negative symptoms, see here for targeted treatment.
It is rarely appropriate to increase the antipsychotic dose above the recommended maximum dose to try to overcome treatment resistance. Dosing above the recommended range is associated with increased adverse effects but rarely improves symptoms. In some cases, a psychiatrist may exceed the recommended maximum dose range (eg if drug metabolism is increased by patient pharmacogenetics or drug interactions).
Although individual studies support adding various drugs (eg minocycline, estrogen, N-acetylcysteine) to antipsychotic therapy for treatment-resistant schizophrenia, this evidence is limited—no specific combination can be recommended except for patients with clozapine-resistant schizophrenia.