Original Paper
11
Authors
F. A. Mustafa, J. G. Burke, S. S. Abukmeil, J. J. Scanlon, M. Cox
Affiliation
Northamptonshire Healthcare NHS Foundation Trust, Northampton, Northamptonshire, UK
Key words ▶ schizophrenia past clozapine ● ▶ clozapine discontinuation ● ▶ clozapine mortality ● ▶ alternative to clozapine ● ▶ olanzapine ●
Abstract
received 25.06.2014 revised 10.08.2014 accepted 29.09.2014 Bibliography DOI http://dx.doi.org/ 10.1055/s-0034-1394397 Published online: November 6, 2014 Pharmacopsychiatry 2015; 48: 11–14 © Georg Thieme Verlag KG Stuttgart · New York ISSN 0176-3679 Correspondence Dr. F. A. Mustafa Campbell House Campbell Square Northampton NN1 3EB United Kingdom [email protected]
▼
Introduction: The clinical records of 190 patients with schizophrenia who discontinued clozapine between 1990 and 2012 in the county of Northamptonshire were examined, in an attempt to answer the following questions. Why do patients stop clozapine? What do physicians prescribe as an alternative? What is the mortality in this patient group? Methods: Patients’ data were extracted using their electronic records, then analysed using descriptive statistical methods. Results: Non-compliance with treatment, or with the mandatory white blood cell monitoring, was the most common reason (55.3 %) for clozapine cessation, followed by neutropaenia and other adverse effects (25.2 %). Death (mean age 48 years) was the third most common reason (10 %), with respiratory infections accounting for more
Introduction
▼
The superiority of clozapine over other antipsychotic drugs in treating refractory schizophrenia has long been established [1, 2]. However, its utilisation has been hampered by its troublesome and potentially serious adverse effects [3]. Due to a lack of effective alternatives, pharmacological management of patients who discontinue clozapine therapy represents a significant clinical challenge [4]. Establishing the factors leading to treatment cessation is necessary for ensuring continuity, safety and optimisation of clozapine treatment. A number of previous studies have shown that noncompliance was the main reason for clozapine discontinuation, followed by adverse effects [5– 7]. Whilst Pai and Vella reported no deaths on clozapine [6], the other 2 studies by Davis et al. [5] and Taylor et al. [7] found that death accounted
than a quarter of the deaths. 13 % of the patients had died (mean age 49 years) at some point following clozapine discontinuation. In terms of the alternative antipsychotic prescribing, olanzapine was the most commonly prescribed (37.1 %) drug in patients who were still under the care of the local psychiatric service (n = 121), at the time of data extraction. Clozapine had been reinstated in 19 % of these patients. Discussion: Our findings are generally consistent with previous studies, and they demonstrate the need for physicians to address their patients’ concerns regarding clozapine treatment, and to effectively manage any adverse effects. Sialorrhea and constipation seem to be particularly of concern, as they may be linked to clozapine – related mortality. Olanzapine was the most commonly prescribed alternative to clozapine, which suggests that it may possibly have a role in refractory schizophrenia.
for 13 % of all cases of clozapine cessation (mean age at death was 55.1 years and 49.2 years, respectively). Furthermore, a recent review [4] indicated that solid evidence regarding treatment for patients with schizophrenia who discontinue clozapine was lacking. Nonetheless, this review suggested that there was modest evidence to support a trial of olanzapine in such cases, especially in patients with less severe illness, and those who discontinue clozapine for reasons other than poor therapeutic response [4]. In the present study, we aim to establish the reasons for clozapine discontinuation as well as the subsequent alternative antipsychotic prescribing, and to explore the mortality in past clozapine patients, in a clinical setting in the county of Northamptonshire, England.
Mustafa FA et al. “Schizophrenia past Clozapine”: Reasons … Pharmacopsychiatry 2015; 48: 11–14
This document was downloaded for personal use only. Unauthorized distribution is strictly prohibited.
“Schizophrenia past Clozapine”: Reasons for Clozapine Discontinuation, Mortality, and Alternative Antipsychotic Prescribing
12 Original Paper
▼
A list of patients who discontinued clozapine treatment at least once, up to December 2012 was obtained through the pharmacy department. Patients’ electronic records were then used in a cross-sectional fashion, to obtain data on diagnosis, age, gender, current service status, reason for clozapine discontinuation as well as the current antipsychotic treatment, as of 1st December 2012. For deceased patients, the cause of death was obtained when available. Reasons for clozapine discontinuation were arbitrarily divided into the following 5 categories: non-compliance with treatment or with mandatory white blood cell (WBC) monitoring, neutropaenia, other adverse effects, physician’s decision, and death. Pearson’s chi-square test and Fisher’s exact test were utilised to examine the relationship between variables. Statistical significance was conventionally set at p
11
Authors
F. A. Mustafa, J. G. Burke, S. S. Abukmeil, J. J. Scanlon, M. Cox
Affiliation
Northamptonshire Healthcare NHS Foundation Trust, Northampton, Northamptonshire, UK
Key words ▶ schizophrenia past clozapine ● ▶ clozapine discontinuation ● ▶ clozapine mortality ● ▶ alternative to clozapine ● ▶ olanzapine ●
Abstract
received 25.06.2014 revised 10.08.2014 accepted 29.09.2014 Bibliography DOI http://dx.doi.org/ 10.1055/s-0034-1394397 Published online: November 6, 2014 Pharmacopsychiatry 2015; 48: 11–14 © Georg Thieme Verlag KG Stuttgart · New York ISSN 0176-3679 Correspondence Dr. F. A. Mustafa Campbell House Campbell Square Northampton NN1 3EB United Kingdom [email protected]
▼
Introduction: The clinical records of 190 patients with schizophrenia who discontinued clozapine between 1990 and 2012 in the county of Northamptonshire were examined, in an attempt to answer the following questions. Why do patients stop clozapine? What do physicians prescribe as an alternative? What is the mortality in this patient group? Methods: Patients’ data were extracted using their electronic records, then analysed using descriptive statistical methods. Results: Non-compliance with treatment, or with the mandatory white blood cell monitoring, was the most common reason (55.3 %) for clozapine cessation, followed by neutropaenia and other adverse effects (25.2 %). Death (mean age 48 years) was the third most common reason (10 %), with respiratory infections accounting for more
Introduction
▼
The superiority of clozapine over other antipsychotic drugs in treating refractory schizophrenia has long been established [1, 2]. However, its utilisation has been hampered by its troublesome and potentially serious adverse effects [3]. Due to a lack of effective alternatives, pharmacological management of patients who discontinue clozapine therapy represents a significant clinical challenge [4]. Establishing the factors leading to treatment cessation is necessary for ensuring continuity, safety and optimisation of clozapine treatment. A number of previous studies have shown that noncompliance was the main reason for clozapine discontinuation, followed by adverse effects [5– 7]. Whilst Pai and Vella reported no deaths on clozapine [6], the other 2 studies by Davis et al. [5] and Taylor et al. [7] found that death accounted
than a quarter of the deaths. 13 % of the patients had died (mean age 49 years) at some point following clozapine discontinuation. In terms of the alternative antipsychotic prescribing, olanzapine was the most commonly prescribed (37.1 %) drug in patients who were still under the care of the local psychiatric service (n = 121), at the time of data extraction. Clozapine had been reinstated in 19 % of these patients. Discussion: Our findings are generally consistent with previous studies, and they demonstrate the need for physicians to address their patients’ concerns regarding clozapine treatment, and to effectively manage any adverse effects. Sialorrhea and constipation seem to be particularly of concern, as they may be linked to clozapine – related mortality. Olanzapine was the most commonly prescribed alternative to clozapine, which suggests that it may possibly have a role in refractory schizophrenia.
for 13 % of all cases of clozapine cessation (mean age at death was 55.1 years and 49.2 years, respectively). Furthermore, a recent review [4] indicated that solid evidence regarding treatment for patients with schizophrenia who discontinue clozapine was lacking. Nonetheless, this review suggested that there was modest evidence to support a trial of olanzapine in such cases, especially in patients with less severe illness, and those who discontinue clozapine for reasons other than poor therapeutic response [4]. In the present study, we aim to establish the reasons for clozapine discontinuation as well as the subsequent alternative antipsychotic prescribing, and to explore the mortality in past clozapine patients, in a clinical setting in the county of Northamptonshire, England.
Mustafa FA et al. “Schizophrenia past Clozapine”: Reasons … Pharmacopsychiatry 2015; 48: 11–14
This document was downloaded for personal use only. Unauthorized distribution is strictly prohibited.
“Schizophrenia past Clozapine”: Reasons for Clozapine Discontinuation, Mortality, and Alternative Antipsychotic Prescribing
12 Original Paper
▼
A list of patients who discontinued clozapine treatment at least once, up to December 2012 was obtained through the pharmacy department. Patients’ electronic records were then used in a cross-sectional fashion, to obtain data on diagnosis, age, gender, current service status, reason for clozapine discontinuation as well as the current antipsychotic treatment, as of 1st December 2012. For deceased patients, the cause of death was obtained when available. Reasons for clozapine discontinuation were arbitrarily divided into the following 5 categories: non-compliance with treatment or with mandatory white blood cell (WBC) monitoring, neutropaenia, other adverse effects, physician’s decision, and death. Pearson’s chi-square test and Fisher’s exact test were utilised to examine the relationship between variables. Statistical significance was conventionally set at p
