Treatment-Resistant Schizophrenia: Assessment and Management

  • Sandeep Grover
  • Harsh Garekar
  • Anisha Agarwal


The concept of treatment resistance in schizophrenia (TRS) grew out of the seminal work of Kane and his coworkers, who for the first time demonstrated the efficacy of clozapine in patients who were previously thought to be treatment unresponsive. Since then the concept of TRS has been refined and elaborated, but it is still used as a primary indicator to initiate clozapine. Clozapine has been conclusively shown to be more effective in TRS for both positive and negative symptoms. In addition to psychotic symptoms, clozapine has been specifically useful in the symptom domains of aggression and suicidality. It has been safely and effectively used in diverse patient groups such as the elderly, children and adolescents, pregnant or postpartum women, and patients with tardive syndromes. Despite good evidence, clozapine has been underutilized in clinical practice worldwide due to its side effects and the apprehension related to its serious side effects such as agranulocytosis, seizures, and myocarditis. In patients who have been on clozapine, despite the significant side effect burden of metabolic syndrome it poses, clozapine has had a positive impact on the quality of life. Around one third of patients with schizophrenia fail to respond adequately to clozapine. For such patients, clozapine augmentation with other agents is a common strategy with a continually growing evidence base. Current knowledge about these augmentation strategies does not support an evidence-based treatment algorithm, but it can aid clinicians in selecting the best treatment based on psychopathology and side effect profile. Among the various augmentation strategies, the best level of evidence is for electroconvulsive therapy.


Clozapine Schizophrenia Treatment resistance Electroconvulsive therapy Drug resistance Antipsychotic agents 


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Copyright information

© Springer Nature Singapore Pte Ltd. 2019

Authors and Affiliations

  • Sandeep Grover
    • 1
  • Harsh Garekar
    • 1
  • Anisha Agarwal
    • 1
  1. 1.Department of PsychiatryPostgraduate Institute of Medical Education and ResearchChandigarhIndia

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