Agranulocytosis is generally defined as when a full blood counts shows neutrophils are less than 0.5 x109/L.
Agranulocytosis is listed as an uncommon side effect4 (≥1/1,000 to <1/100) in patients on clozapine treatment and should not be a barrier to prescribing it for patients with TRS who may benefit significantly from it.
In two clinical studies with a total of 250 patients treated with clozapine, four patients developed agranulocytosis (1.6%), all of whom recovered after treatment discontinuation.1,2
Viatris offer several support services including the UK Clozaril® Patient Monitoring Service (CPMS). The CPMS monitors patients’ white blood cell counts and absolute neutrophil counts (ANC) and is a vital resource for maintaining patient safety while on Clozaril®. Although mortality rates due to agranulocytosis are low (estimated at 0.3%)3 when a monitoring service is not used, regular blood monitoring by the CPMS can markedly reduce mortality risk due to agranulocytosis to 0.01%,4 an absolute risk reduction of 0.29%.
Weight gain
Weight gain with Clozaril® is listed as a common side effect4 (≥1/100 to <1/10) but this should not be a barrier to prescribing it.
Two systematic reviews – one comparing clozapine with typical antipsychotics and one comparing clozapine with typical and atypical antipsychotics – found that weight gain occurred at a similar frequency in patients on clozapine and on typical/atypical antipsychotics.5, 6
In a clinical study, weight gain while on clozapine therapy has been shown to be less than, or similar to, that for patients on the atypical antipsychotics olanzapine, risperidone, and quetiapine.2
Other adverse events (AEs)
Adverse events with Clozaril® are similar to those experienced on other antipsychotics
Clinical studies and meta-analyses indicate that adverse events (AEs) associated with Clozaril® are generally similar to those of other typical and atypical antipsychotics including chlorpromazine, haloperidol, risperidone and olanzapine. These include hypotension, seizures, sedation, and weight gain.5, 7, 8
Dizziness, salivation, and nausea have been noted more frequently for clozapine compared with the typical antipsychotics haloperidol and chlorpromazine, whereas dry mouth and extrapyramidal symptoms have been reported more frequently with the latter.8-11
A summary of the main AE findings in clinical studies and meta-analyses is given in Table 2.
Table 2. Adverse events findings in clinical studies and meta-analyses comparing Clozaril® and other antipsychotics
Study
Clozaril® comparator
Main AEs findings
Kane, et al. 2001
Clinical, 71 patients
Haloperidol
At week 5, no differences between treatments were observed for occurrence of 12 of the 17 AEs
listed under the Treatment Emergent Symptoms Scale.
Azorin, et al. 2001
Clinical, 273 patients
Risperidone
Of the 15 different AEs occurring in at least 5% of patients, no difference in incidence was observed
between treatments were observed for eight of them.
The proportion of patients experiencing any moderate or severe AEs was not significantly different
between treatments.
Of the 10 categories of AE identified, no significant differences in incidence between treatments were
observed for seven of them
Wahlbeck, et al. 1999
Meta-analysis
Typical antipsychotics
No difference was found between treatments for hypotension/dizziness, seizures, or weight gain.
Clozaril® caused more hypersalivation, temperature increase, and sedation but less dry mouth and
extrapyramidal symptoms.
Essali, et al. 2009
Cochrane meta-analysis
Typical antipsychotics
No significant differences between treatments were found in the incidences of low blood pressure/dizziness.
Dry mouth occurred more frequently in the typical antipsychotic group.
Clozaril® caused more salivation and weight gain.
Chakos, et al. 2001
Meta-analysis
Olanzapine
Risperidone
Haloperidol
Chlorpromazine
Clozaril® was associated with similar frequencies of hypotension to olanzapine and risperidone;
sedation to haloperidol and olanzapine, and concentration problems to chlorpromazine.
If patients are not given adequate information about their condition and their medication, they may fail to see the real value in adhering to their treatment. Poor adherence to therapy may lead to suboptimal outcomes.
Only 4 in 10 (41%) schizophrenia patients feel adequately involved in decisions regarding their drug prescriptions (NAS, 2014)12
Only 4 in 10 (39%) schizophrenia patients are given information about their medication in a form they can easily understand (NAS, 2014)12
Solution Giving patients more information about their schizophrenia and their drug prescriptions in an accessible form can help to build trust between the patient and the HCP. Greater trust in the doctor/patient relationship may improve adherence to therapy and hence outcomes.
Lack of access to point-of care testing
In the past, access to a point-of-care (POC) testing device was linked to a number of Clozaril® patients for blood monitoring while on treatment.
Solution As part of Viatris's endeavour to improve access to Clozapine for TRS patients, Viatris can provide a POC device and training to any sites with the required resources, enabling patients' bloods to be tested locally.
HCP and patient information on Clozaril®
You may be concerned that you do not have adequate information on Clozaril® for healthcare professionals (HCP) and patients.
SolutionViatris has two websites - one for healthcare professionals and one for patients.
Rosenheck R, Cramer J, Xu W, Thomas J, Henderson W, Frisman L, et al for the Department of Veterans Affairs Cooperative Study Group on Clozapine in Refractory Schizophrenia. A comparison of clozapine and haloperidol in hospitalized patients with refractory schizophrenia. N Engl J Med 1997; 337: 809-15.
McEvoy JP, Lieberman JA, Stroup TS, Davis SM, Meltzer HY, Rosenheck RA, et al. Effectiveness of clozapine versus olanzapine, quetiapine, and risperidone in patients with chronic schizophrenia who did not respond to prior atypical antipsychotic treatment. Am J Psychiatry 2006; 163: 600-10.
de la Chapelle A, Kari C, Nurminen M, Hernberg S. Clozapine-induced agranulocytosis. A genetic and epidemiologic study. Hum Genet 1977; 37: 183-94.
Wahlbeck K, Cheine M, Essali A, Adams C. Evidence of clozapine’s effectiveness in schizophrenia: a systematic review and meta-analysis of randomized trials. Am J Psychiatry 1999; 156: 990-9.
Siskind D, McCartney L, Goldschlager R, Kisely S. Clozapine v. first- and second-generation antipsychotics in treatment-refractory schizophrenia: systematic review and meta-analysis. Br J Psychiatry 2016; 209: 385-92.
Chakos M, Lieberman J, Hoffman E, Bradford D, Sheitman B. Effectiveness of second-generation antipsychotics in patients with treatment-resistant schizophrenia: a review and meta-analysis of randomized trials. Am J Psychiatry 2001; 158: 518-26.
Essali A, Al-Haj Haasan N, Li C, Rathbone J. Clozapine versus typical neuroleptic medication for schizophrenia. Cochrane Database Syst Rev. 2009 Jan 21; (1): CD000059.pub2.
Kane J, Marder S, Schooler N, Wirshing W, Umbricht D, Baker R, et al. Clozapine and haloperidol in moderately refractory schizophrenia: a 6-month randomized double-blind comparison. Arch Gen Psychiatry 2001; 58: 965-72.
Azorin JM, Spiegel R, Remington G, Vanelle JM, Pere JJ, Giguere M, et al. A double-blind comparative study of clozapine and risperidone in the management of severe chronic schizophrenia. Am J Psychiatry 2001; 158: 1305-13.
Buchanan RW, Breier A, Kirkpatrick B, Ball P, Carpenter WT. Positive and negative symptom response to clozapine in schizophrenic patients with and without the deficit syndrome. Am J Psychiatry 1998; 155: 751-60.
National Audit of Schizophrenia (NAS). Second National Audit of Schizophrenia: What you need to know. The Royal College of Psychiatrists, 2014.
UK-CLZ-2025-00015 March 2026
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