Delay and reluctance to prescribe Clozapine: British Jl Psy.Dec.2012.


All clinical guidelines endorse  early use of clozapine in resistant schizophrenia. Do patients really get the benefits of this medication? Are clinicians reluctant to use clozapine?

Howes et al  reports that of the 149 patients who started  clozapine between 2006-2010, the  mean theoretical  delay for clozapine initiation was 48 months . One third of patients had antipsychotic polypharmacy and one third were on high dose antispychotics bofore starting clozapine.Patients received more than five different antipsychotic treatment episodes before clozapine initiation.

The retrospective design and the fact that the study excluded a third of eligible patients owing to missing clinical notes are notable limitations of this study. The clinical reasons for this theoretical delay are  missing. It might include the difficulties in achieving two adequate trials of  antipsychotics in terms of dose, duration and adherence.

Reluctance to start clozapine is reported  from elsewhere as well. Nielson et al (2010,Danish study)  reported that two-thirds of psychiatrists interviewed would rather combine two antipsychotics than use clozapine.

In the accompanying editorial Maxine.X.Patel asks the key question- Why are clinicians delaying clozapine initiation?  Clinician perception that clozapine is a dangerous medication (Farooq &Taylor 2011) is a key theme in this.In UK, clozapine was observed to be associated with increased risk of death and that pneumonia was the most common single cause (Taylor 2009).A large scale study from Finland  found that risk for all-cause mortality for antipsychotics was  lowest for clozapine, and this was attributed in particular to a lower risk of death from suicide(Tiihonen  2009).Other factors highlighted in this under utilisation include weight gain, hypersalivation and blood monitoring. Also of note is that a quarter of psychiatrists overestimated the risk of agranulocytosis.

What do we do?  Maxine’s editorial suggests various areas that could improve the use of clozapine.

1.Knowledge, attitudes, preferences- this is key to any change in prescribing behaviour. Particular focus should be around perception of side effects and knowledge of their management.The ambivalence regarding clozapine’s superior efficacy in resistant cases also needs to be addressed.

2. The worry about patient attitudes to and adherence with clozapine and the associated regular blood tests- is it part of a paternalistic attitude?

3. Access to a laboratory for drug plasma concentration levels and easy access to phlebotomy service

4. Ongoing experiential knowledge of prescribing clozapine.

5.Endorsement by members of the multi- disciplinary team.

Comment: One potential reason for under utilisation is patient refusal of clozapine. Suggesting clozapine is at times interpreted by patients and families as ‘ final option”.Educating patients and carers of the benefits of clozapine is also essential.

Summary of the articles:

Adherence to treatment guidelines in clinical practicestudy of antipsychotic treatment prior to clozapine initiation.

Howes OD, Vergunst F, Gee S, McGuire P, Kapur S, Taylor D. Br J Psychiatry. 2012 Dec;201:481-5.

Clinician hesitation prior to clozapine initiation: is it justifiable? Patel MX. Br J Psychiatry. 2012 Dec;201:425-7.

2 thoughts on “Delay and reluctance to prescribe Clozapine: British Jl Psy.Dec.2012.

  1. Yes, its true that clinicians do hesitate to start clozapine. The complex dosing system may be one of the reason apart from the concerns about potential fatal side effects. The availability of monitoring drug level is also a contributory factor.

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