This article was published on June 20, 2022. It was last updated/ edited on August 4, 2022.
Please read this article carefully even if you don’t prescribe clozapine yourself.
All of us can help by referring patients with treatment-resistant schizophrenia for treatment with clozapine more often and earlier than is currently being done. And, this is really important.
On another page, we discussed the unique advantages of clozapine and why it needs to be prescribed more often. Please see the following article on this website:
Why we must refer more patients for clozapine treatment
But despite these advantages, clozapine is being greatly underutilized and, even when it is prescribed, this is typically done after long delays.
Underutilization and Delays
All over the world and in various types of treatment settings:
1. Only a small percentage of patients who should receive clozapine are being treated with it (Bogers et al., 2016; Warnez and Alessi-Severini, 2014).
2. The start of clozapine treatment is typically delayed for many years from the point when it should have been started (Farooq et al., 2019).
An inappropriate delay in starting clozapine is possibly related to worse outcomes of treatment even after clozapine is started (Shah et al., 2018
For example, in one case-control study, in patients with “treatment-resistant” schizophrenia whose illness did not respond to clozapine, there had been a longer delay before clozapine was started (Chan et al., 2021).
What about the potentially serious side effects of clozapine?
1. One of the main reasons for the underutilization of clozapine is concern about the potentially serious side effects of clozapine (Farooq et al., 2019).
That is a valid concern but here are some counterarguments:
– Clinicians experienced in using clozapine are usually able to prevent and manage most of the side effects of clozapine. For example, due to close monitoring, agranulocytosis is rarely seen in clinical practice (Baig et al., 2021).
– Also, the potential risks of clozapine should be balanced against the potential benefits in terms of efficacy and, possibly, lower mortality (Bogers et al., 2016).
– Clinicians tend to overestimate how common the side effects of clozapine are and how they affect patients (Baig et al., 2021). On the other hand, they underestimate how satisfied patients on clozapine are with the treatment (Baig et al., 2021).
Other barriers to clozapine use
2. Clinicians’ lack of knowledge and training about clozapine (Baig et al., 2021; Farooq et al., 2019).
3. Poor adherence to the medication and/or the required monitoring (Baig et al., 2021; Farooq et al., 2019). In several surveys, psychiatrists reported that many patients completely refuse to get the required blood tests (Farooq et al., 2019). But, are there ways in which patients can be engaged more effectively in accepting clozapine treatment?
Access to clozapine prescribers must be increased
1. Many more clinicians who regularly treat patients with schizophrenia and schizoaffective disorder should decide to get some additional training in using clozapine, including managing its potential side effects.
If you are interested in doing this, please email me at firstname.lastname@example.org and let me know. We will help you in doing this.
2. Those who don’t see patients with schizophrenia and schizoaffective disorder regularly or for some other reason don’t want to prescribe clozapine should identify clinicians in their area who prescribe clozapine and refer appropriate patients to them for clozapine treatment.
For how to locate a clozapine prescriber, please see the following article on this website: Where can I find someone who prescribes clozapine?
3. If you are a clozapine prescriber but have not yet registered with the CureSZ Foundation’s database of clozapine prescribers, please email me at email@example.com with your name, office address, and office phone number.
Clozapine prescribers must be supported
Clinicians with less experience in prescribing clozapine should seek out more experienced clozapine prescribers whom they can consult about any problems that may arise (Love et al., 2016).
Clinicians who regularly prescribe clozapine should consider establishing a relationship with a primary care practice to help with managing the side effects of clozapine (Love et al., 2016).
Fingerstick blood testing should be widely adopted
Given then getting blood draws as per the required schedule is a pain in the you-know-what, point-of-care, portable devices for measuring white blood cell and neutrophil counts using a fingerstick to obtain capillary blood are preferred by patients (Kamhi-Nesher et al., 2022; Kelly et al., 2021; Atkins et al., 2021; Taylor et al., 2021).
But, if the values are outside the normal range, confirmatory testing using a conventional venous blood draw should be done (Atkins et al., 2021).
In the United States, as of August 2022, a commercial device for fingerstick testing of the white blood cell and absolute neutrophil counts has been cleared by the FDA for clinical use and has been adopted in thousands of clinics. It is called Athelas One® (website).
Disclaimer: Simple and Practical Education has no relationship of any kind with the manufacturer of Athelas One and, since we have not independently evaluated the device, the information provided about the device is for general educational purposes only.
Patients receiving clozapine should be grouped together
1. Treatment facilities should strongly consider establishing a “clozapine clinic” so that practices related to clozapine prescribing and monitoring can be streamlined. Ideally, such clinics should be run by an interdisciplinary team. But, even if that is not possible, such a clinic must have at least one staff member who helps the prescribing clinician with the administrative tasks involved in prescribing clozapine.
2. Similarly, individual clinicians should consider having a fixed day of the week when they see all their patients who are on clozapine—a “clozapine day”.
Education and support must be provided to patients and their families
Clozapine groups should be offered to patients and families for providing education and support related to clozapine treatment (Love et al., 2016).
Clozapine (Clozaril®): Basic Information
Why we must refer more patients for clozapine treatment
What can we do about the underutilization of clozapine and delays in starting it?
Where can I find someone who prescribes clozapine?
Clozapine for schizophrenia in children?
Changes in rules about clozapine
How to check and interpret clozapine levels
Are the clozapine-norclozapine ratio and norclozapine level useful?
Can oral contraceptives affect clozapine levels?
Caffeine can significantly change serum clozapine levels
Potential side effects of clozapine (Clozaril®) handout
Key information about seizures with clozapine
Clozapine-induced hypersalivation (sialorrhea)
Clozapine-induced hypersalivation (sialorrhea): Treatment
Benign ethnic neutropenia (BEN)
Let’s explicitly identify patients with “treatment-resistant” schizophrenia
Atkins M, McGuire P, Balgobin B, Patel P, Taylor D. Using a fingerstick test for haematological monitoring in patients treated with clozapine. Ther Adv Psychopharmacol. 2021 Mar 25;11:20451253211000865. doi: 10.1177/20451253211000865. PMID: 33854764; PMCID: PMC8010800.
Baig AI, Bazargan-Hejazi S, Ebrahim G, Rodriguez-Lara J. Clozapine prescribing barriers in the management of treatment-resistant schizophrenia: A systematic review. Medicine (Baltimore). 2021 Nov 12;100(45):e27694. doi: 10.1097/MD.0000000000027694. PMID: 34766570.
Bogers JP, Schulte PF, Van Dijk D, Bakker B, Cohen D. Clozapine Underutilization in the Treatment of Schizophrenia: How Can Clozapine Prescription Rates Be Improved? J Clin Psychopharmacol. 2016 Apr;36(2):109-11. doi: 10.1097/JCP.0000000000000478. PMID: 26872120.
Farooq S, Choudry A, Cohen D, Naeem F, Ayub M. Barriers to using clozapine in treatment-resistant schizophrenia: systematic review. BJPsych Bull. 2019 Feb;43(1):8-16. doi: 10.1192/bjb.2018.67. Epub 2018 Sep 28. PMID: 30261942; PMCID: PMC6327301.
Kamhi-Nesher S, Taub S, Halimi S, Frenkel M, Azam M, Bormant G, Isakov H, Radzinsky D, Weizman A, Krivoy A. Clozapine blood level assessment using a point-of-care device: feasibility and reliability. Ther Adv Psychopharmacol. 2022 Jun 14;12:20451253221094435. doi: 10.1177/20451253221094435. PMID: 35720508; PMCID: PMC9201354.
Kelly DL, Freudenreich O, Sayer MA, Love RC. Addressing Barriers to Clozapine Underutilization: A National Effort. Psychiatr Serv. 2018 Feb 1;69(2):224-227. doi: 10.1176/appi.ps.201700162. Epub 2017 Oct 16. PMID: 29032704; PMCID: PMC8581998.
Kelly DL, Ponomareva OY, Mackowick M, Glassman M, Park J, Navarro-De La Vega M, Wehring HJ, Vyas G. Feasibility and patient-reported satisfaction using a novel point-of-care fingerstick method for monitoring absolute neutrophil count for clozapine. Ann Clin Psychiatry. 2021 May;33(2):116-123. doi: 10.12788/acp.0029. PMID: 33878286.
Love RC, Kelly DL, Freudenreich O, Sayer M; National Association of State Mental Health Program Directors. Clozapine Underutilization: Addressing the Barriers (2016). Available at THIS LINK. Webinar on this topic is available at THIS LINK. Both links were last accessed on August 4, 2022.
Rubio JM, Kane JM. How to Make an Effective Offer of Clozapine. J Clin Psychiatry. 2021 Nov 30;83(1):21ac14000. doi: 10.4088/JCP.21ac14000. PMID: 34851559.
Shah P, Iwata Y, Plitman E, Brown EE, Caravaggio F, Kim J, Nakajima S, Hahn M, Remington G, Gerretsen P, Graff-Guerrero A. The impact of delay in clozapine initiation on treatment outcomes in patients with treatment-resistant schizophrenia: A systematic review. Psychiatry Res. 2018 Oct;268:114-122. doi: 10.1016/j.psychres.2018.06.070. Epub 2018 Jul 9. PMID: 30015109.
Taylor D, Atkins M, Harland R, Baburina I, MacCabe JH, Salamone SJ, McGuire P. Point-of-care measurement of clozapine concentration using a finger-stick blood sample. J Psychopharmacol. 2021 Mar;35(3):279-283. doi: 10.1177/0269881121991567. Epub 2021 Feb 12. PMID: 33579175.
Verdoux H, Quiles C, Bachmann CJ, Siskind D. Prescriber and institutional barriers and facilitators of clozapine use: A systematic review. Schizophr Res. 2018 Nov;201:10-19. doi: 10.1016/j.schres.2018.05.046. Epub 2018 Jun 4. PMID: 29880453.
Warnez S, Alessi-Severini S. Clozapine: a review of clinical practice guidelines and prescribing trends. BMC Psychiatry. 2014 Apr 7;14:102. doi: 10.1186/1471-244X-14-102. PMID: 24708834; PMCID: PMC3999500.
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