How to manage Treatment Resistant Schizophrenia? WFSBP guidelines:2012-2013.


10–30% of individuals with schizophrenia show little or no response to antipsychotic medications.Treatment resistance ie  lack of significant improvement of psychopathology and/or other target symptoms despite treatment with two different antipsychotics from at least two different chemical classes (at least one should be an atypical antipsychotic) in the previous five years at the recommended antipsychotic dosages for a treatment period of at least 2–8 weeks per drug, occurs in up to 65% of individuals with schizophrenia when functional impairments are also considered.

ALKOMIET HASAN et al reports the  World Federation of Societies of Biological Psychiatry (WFSBP) Guidelines for Biological Treatment of Schizophrenia in this issue. It covers acute treatment as well as treatment resistant schizophrenia (TRS). (Recommendations regarding TRS  alone is summarised here).

In suspected TRS , Suboptimal dose, ongoing substance abuse, neurobiological factors (e.g., morphological brain abnormalities), environmental factors (e.g., unfavourable familial atmosphere, high expressed emotions) and pharmacodynamic reasons should be explored as causing or contributing to resistance.The target symptoms should be precisely defined. Compliance should be ensured, if necessary by checking drug concentrations.


  • A switch from an initially unsuccessful FGA to another FGA seems to be ineffective and a switch to an SGA should instead be taken into consideration. Changing from one FGA to another FGA resulted in fewer than 5% of the patients achieving a satisfying therapeutic response .Doses higher than 400 CPZ  do not lead to more efficacy. A meta-analysis of 12 controlled trials showed that SGAs exhibit superiority in the management of TRS compared to FGAs. The results, except for clozapine, are inconclusive.
  • Clozapine should be considered as first-line treatment in TRS. A dosage range of 100–900 mg  (mean 400mg/day) or a blood level of more than 350 ng/ml should be aimed. CUtLASS 2 trial showed an advantage of clozapine in reducing positive and negative symptoms in TRS  compared to four established SGAs (ziprasidone, olanzapine, quetiapine, amisulpride). Phase II of the CATIE-study  showed that clozapine is more effective than  quetiapine and risperidone, but not to olanzapine  in patients who failed to respond to one SGA.
  • In cases of clozapine intolerance a switch to another SGA, preferentially olanzapine or risperidone, should be performed. There are few data to support amisulpride, aripiprazole and quetiapine being effective as monotherapy in TRS.
  • There is no evidence for the efficacy of asenapine, iloperidone, lurasidone and paliperidone in TRS.
  • Dose escalation, unless side effects lead to an earlier drug switching, was previously recommended  but recent studies do not support this statement.
  • When patients show a partial response to treatment, extend the duration of the trial  to 4–10 weeks for the initial antipsychotic and 5–11 weeks for the second antipsychotic prescribed.Sometimes symptoms can continue to improve over the course of 6 months.Waiting of 3-6 weeks is good enough to stop the medication if there is no response at all.

    Summary of the article:

    World Federation of Societies of Biological Psychiatry (WFSBPGuidelines for Biological Treatment of Schizophreniapart 1:update 2012 on the acute treatment of schizophrenia and the management of treatment resistance.

    Hasan A, Falkai P, Wobrock T, Lieberman J, Glenthoj B, Gattaz WF, Thibaut F, Möller HJ; World Federation of Societies of BiologicalPsychiatry (WFSBP) Task Force on Treatment Guidelines for SchizophreniaWorld J Biol Psychiatry2012

    The 2013 Feb  article :WFSB guidelines on longterm management of schizophrenia/ management of side effects will be summarised on 13.02.2013.

One thought on “How to manage Treatment Resistant Schizophrenia? WFSBP guidelines:2012-2013.

  1. I am surprise to see absence of mention of ECT..second about compination of clozapine and amisulpride third role of lamotrigine

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