Delay in Starting Clozapine in Treatment Resistant Schizophrenia – Why it Matters

Posted on April 13, 2017

Schizophrenia is a severe mental illness that is characterised by psychotic symptoms such as delusions, hallucinations, social withdrawal and cognitive impairment. Schizophrenia has a high morbidity and mortality rate. A recent systematic review and meta-analysis showed that Schizophrenia was associated with a weighted average of 14·5 years of potential life lost and was higher for men than women. The overall weighted average life expectancy was 64·7 years and was lower for men than women. [1]

Treatment-resistant schizophrenia (TRS) describes patients who fail to respond to pharmacotherapy and the widely accepted definition is a non or inadequate response to at least two antipsychotics of adequate dose for an adequate duration.  It is estimated that anywhere between 20 – 45 % of patients are partial responders to treatment with 5 – 10 % of patients receiving no apparent benefit [2]. Clozapine is an atypical antipsychotic that is considered first line in TRS [3].

A recently published paper at the Okayama Psychiatric Medical Center in Japan attempted to understand the critical nature of the clozapine treatment window in TRS. Their aim was to determine the symptomatic outcomes of TRS and the delay in initiating clozapine treatment.


1. Schizophrenia Life Expectancy

Hjorthøj, C., Stürup, A. E., McGrath, J. J., & Nordentoft, M. (2017). Years of potential life lost and life expectancy in schizophrenia: a systematic review and meta-analysis. The Lancet Psychiatry.

2. Treatment Resistant Schizophrenia - Prevalence
Pantelis, C., & Lambert, T. J. (2003). Managing patients with” treatment-resistant” schizophrenia. Medical Journal of Australia, 178(9), S62.
3. Treatment Resistant Schizophrenia

Chakos M, et al., Effectiveness of second-generation antipsychotics in patients with treatment-resistant schizophrenia: a review and meta-analysis of randomized trials. American Journal of Psychiatry. 2001

4. Clozapine: dangerous orphan or neglected friend?
Farooq, S., & Taylor, M. (2011). Clozapine: dangerous orphan or neglected friend?. The British Journal of Psychiatry, 198(4), 247-249.
5. The Critical Period for Initiation of Clozapine

Yoshimura BY, et al. The critical treatment window of clozapine in treatment-resistant schizophrenia: secondary analysis of an observational study. Psychiatry Research. 2017

6. Do clinicians choose Polypharmacy over Clozapine?

Howes OD, et al. Adherence to treatment guidelines in clinical practice: study of antyipsychotic treatment prior to clozapine initiation. British Journal of Psychiatry. 2012

7. Delay in clozapine and Outcome

Üçok A, et al. Delayed initiation of clozapine may be related to poor response in treatment-resistant schizophrenia. International Clinical Psychopharmacology. 2015