Introduction
Individuals diagnosed with schizophrenia experience substantial excess medical morbidity and mortality, with an estimated 10- to 20-year shorter life expectancy compared to the general population (Chesney et al. Reference Chesney, Goodwin and Fazel2014, Westman et al. Reference Westman, Eriksson, Gissler, Hällgren, Prieto, Bobo, Frye, Erlinge, Alfredsson and Ösby2018, Ali et al. Reference Ali, Santomauro, Ferrari and Charlson2023). Cardiovascular and metabolic issues are contributing factors to this phenomenon and research demonstrates that the relative risk of developing metabolic syndrome is 58% higher in individuals with severe mental illness in comparison to the general population (Vancampfort et al. Reference Vancampfort, Stubbs, Mitchell, De Hert, Wampers, Ward, Rosenbaum and Correll2015).
Metabolic syndrome, previously known as syndrome X, is a cluster of medical disorders including elevated blood pressure, obesity, dyslipidaemia and alterations in glucose metabolism (Alberti et al. Reference Alberti, Zimmet and Shaw2006). Metabolic syndrome and its components can lead to the development of cardiovascular disease, hepatic steatosis and type 2 diabetes mellitus (Tariq et al. Reference Tariq, Nayudu, Akella, Glandt and Chilimuri2016). The increased cardio-metabolic risk in service users with severe mental illness is multifactorial (Firth et al. Reference Firth, Siddiqi, Koyanagi, Siskind, Rosenbaum, Galletly, Allan, Caneo, Carney, Carvalho, Chatterton, Correll, Curtis, Gaughran, Heald, Hoare, Jackson, Kisely, Lovell, Maj, McGorry, Mihalopoulos, Myles, O’Donoghue, Pillinger, Sarris, Schuch, Shiers, Smith, Solmi, Suetani, Taylor, Teasdale, Thornicroft, Torous, Usherwood, Vancampfort, Veronese, Ward, Yung, Killackey and Stubbs2019). Genetic and lifestyle factors play a role, but additionally, over the past 20 to 25 years, it has become increasingly recognised that antipsychotic medications are associated with an increased risk of being diagnosed with metabolic syndrome (Holt et al. Reference Holt, Peveler and Byrne2004).
Second-generation antipsychotic medications in particular have been shown to cause weight gain, abdominal obesity, lipid and glucose metabolism alterations, and insulin resistance (Rojo et al. Reference Rojo, Gaspar, Silva, Risco, Arena, Cubillos-Robles and Jara2015). Clozapine, a second-generation antipsychotic medication with established efficacy for treatment-resistant schizophrenia, typically initiated after two other antipsychotics have been ineffective, is associated with a particularly significant adverse impact on metabolic parameters and dysregulation of adipose tissue homeostasis (Ahmed et al. Reference Ahmed, Hussain, O’Brien, Dineen, Griffin and McDonald2008, Rummel-Kluge et al. Reference Rummel-Kluge, Komossa, Schwarz, Hunger, Schmid, Lobos, Kissling, Davis and Leucht2010, Kristóf et al. Reference Kristóf, Doan-Xuan, Sárvári, Klusóczki, Fischer-Posovszky, Wabitsch, Bacso, Bai, Balajthy and Fésüs2016). However, clozapine has the lowest risk of treatment failure and is associated with the most beneficial mortality outcome in terms of all-cause mortality, including cardiovascular and suicide mortality, when compared to other antipsychotic medications (Tiihonen et al. Reference Tiihonen, Mittendorfer-Rutz, Majak, Mehtälä, Hoti, Jedenius, Enkusson, Leval, Sermon, Tanskanen and Taipale2017, Taipale et al. Reference Taipale, Tanskanen, Mehtälä, Vattulainen, Correll and Tiihonen2020).
Service users treated with clozapine have frequent contact with mental health staff due to the mandatory requirement of full blood count monitoring to screen for neutropenia. Dedicated nurse-led clozapine clinics in Ireland provide a forum to facilitate learning around healthy exercise and dietary habits, two modifiable lifestyle factors that contribute to the development of metabolic syndrome (Pitsavos et al. Reference Pitsavos, Panagiotakos, Weinem and Stefanadis2006, Firth et al. Reference Firth, Siddiqi, Koyanagi, Siskind, Rosenbaum, Galletly, Allan, Caneo, Carney, Carvalho, Chatterton, Correll, Curtis, Gaughran, Heald, Hoare, Jackson, Kisely, Lovell, Maj, McGorry, Mihalopoulos, Myles, O’Donoghue, Pillinger, Sarris, Schuch, Shiers, Smith, Solmi, Suetani, Taylor, Teasdale, Thornicroft, Torous, Usherwood, Vancampfort, Veronese, Ward, Yung, Killackey and Stubbs2019). People with severe mental illness have been found to consume diets higher in calories with previous research noting that individuals with schizophrenia engaged in less physical activity than approximately 80% of the general population (Firth et al. Reference Firth, Stubbs, Teasdale, Ward, Veronese, Shivappa, Hebert, Berk, Yung and Sarris2018a, Firth et al. Reference Firth, Stubbs, Vancampfort, Schuch, Rosenbaum, Ward, Firth, Sarris and Yung2018b, Teasdale et al. Reference Teasdale, Ward, Samaras, Firth, Stubbs, Tripodi and Burrows2019). There is an opportunity in clozapine clinics to offer consistent support and feedback in relation to physical health and dietary habits amongst other lifestyle factors including restorative sleep and social relationships (Noordsy et al. Reference Noordsy, Abbott-Freg and Chawla2024). Indeed, a recent study, albeit not in a cohort of individuals with severe mental illness, has demonstrated that knowledge around metabolic syndrome can directly influence dietary behaviour, whilst perceived social support can directly influence dietary behaviour and indirectly influence exercise behaviour (Chen et al. Reference Chen, Zhang, Shao, Tang, Cui, Wang, Wu, Wang and Ye2023). To date, there is a paucity of research examining the awareness of metabolic syndrome in schizophrenia. One recent qualitative study which included 20 individuals prescribed second-generation antipsychotic medication, 12 of whom were diagnosed with schizophrenia, reported a limited awareness of the need for metabolic monitoring (Poojari et al. Reference Poojari, Mey, Khan, SHenoy, Pai, Shetty, Bhat, Bhandary, Acharya, Bose and Thunga2025).
The aim of this study was to evaluate awareness of metabolic syndrome, measure lifestyle habits and assess attitudes towards physical health screening in a cohort of service users attending a dedicated clozapine clinic.
Methods
This was a cross-sectional study of service users attending a clozapine clinic, utilising chart reviews and surveys with assistance provided to support participants.
Questionnaire design
A descriptive questionnaire utilising Likert scales to measure awareness and understanding of metabolic syndrome, current dietary and exercise habits, and attitudes towards physical health checks was utilised in this study. The study questionnaire was developed by a multidisciplinary team including two experienced psychiatrists (significant clinical and research experience with this research cohort, CMcD,BH), a medical doctor (YF) and three nurses working in the clozapine clinic with wider discussions initially held with members of a multidisciplinary community mental health team including community mental health nurses, occupational therapist, social worker, addiction counsellor and psychologist. World Health Organisation (2005) and Health Service Executive (2018) guidelines on healthy eating and exercise regimes helped inform the development of the questionnaire. Three subsequent meetings were held after the initial questionnaire was developed with any disputes regarding specific questions resolved by consensus. The final disseminated questionnaire consisted of 18 items (demographic details = 2, awareness of metabolic syndrome = 2, dietary patterns = 3, exercise patterns = 2, smoking patterns = 1, attitudes towards metabolic monitoring = 8). An effort was made to use non-medical terminology to ensure that participants had a clear understanding of what was being addressed in each section (see supplementary material).
Participants
All service users invited to participate in this study attended a dedicated clozapine clinic at University Hospital Galway. Inclusion criteria for the study required participants to 1) be on clozapine treatment, 2) be over 18 years of age and 3) have capacity to provide written informed consent for study participation. Participants were excluded if they fulfilled criteria for an intellectual disability (intelligence quotient < 70) or had a confirmed diagnosis of dementia. Research interviews were undertaken by one clinician (YF). All responses were anonymised and all data was stored securely and handled in accordance with the Data Protection Act, 2018. Ethical approval was granted prior to study’s commencement by the Galway University Hospitals Research Ethics Committee (C.A. 1462).
Procedures
For individuals who provided written informed consent, clinical case notes were reviewed to obtain basic demographic and clinical data. Demographic data included age, gender, marital, domiciliary and employment or vocational status. Clinical data included psychiatric diagnosis, dose of clozapine, duration of clozapine treatment, co-morbid mental health disorder, physical illness, other prescribed psychotropic medications including first- or second-generation antipsychotic medication (FGA/SGA), alcohol, tobacco and psychoactive substance use.
Medications for physical health conditions associated with metabolic syndrome (anti-hypertensives, lipid-lowering medications, diabetic medications) were recorded. Data pertaining to body mass index (BMI), abdominal waist circumference, blood pressure, and lipid profile data including cholesterol, triglyceride, high-lipid density (HDL), low-lipid density (LDL), and glucose or HbA1C over the previous year was also recorded. A diagnosis of metabolic syndrome was based on the International Diabetes Federation (IDF) criteria (Alberti et al. Reference Alberti, Zimmet and Shaw2006).
The diagnostic parameters of waist circumference and fasting blood glucose were used in the first instance in accordance with the IDF criteria. However, if waist circumference or fasting blood glucose measurements were not available, proxy measures of central obesity (weight in kilograms or Body Mass Index) or impaired glucose tolerance (HbA1c ≥ 42mmol/mol) were used. All laboratory data examined was analysed at the biochemistry laboratory at University Hospital Galway.
Assessments
A semi-structured interview was conducted either in person (n = 48) or by telephone (n = 21) with participants between June 1st and August 15th 2020. Where required, when not available in the clinical notes, information pertaining to physical health, current domiciliary status, employment or vocational status was also collected during these interviews.
Statistical analysis
Statistical analysis was performed using the Statistical Package for Social Sciences 26.0 for Windows (SPSS Inc., IBM, New York, USA). Descriptive analyses of key demographic and clinical data were performed for both categorical and continuous variables, as appropriate. The prevalence of metabolic syndrome and its individual components within the previous year was calculated. We utilised the student t-test for parametric data and the Chi square (x2) test for non-parametric data when comparing demographic data between respondents and non-respondents. All statistical tests were two-sided and the level for statistical significance was 0.05.
Results
Demographic and clinical data
Of the 142 participants attending or supported by the dedicated clozapine clinic, 12 did not meet inclusion criteria (dementia = 4, lacked capacity to consent to participate = 8), and thus 130 were invited to participate. Of these, 61 declined to participate, resulting in 69 study participants (53.1% response rate). Data for the 69 study participants is presented in Table 1. Of note, the majority (n = 50, 72.5%) of participants were male and the mean age of participants was 45.2 ± 10.6 years. Sixty-five (94.2%) participants had a diagnosis of schizophrenia and the mean duration of clozapine treatment was 12.2 ± 7.4 years. Seven individuals had a co-morbid mental health disorder, most commonly an anxiety disorder (n = 6) (see Table 1).
Table 1. Demographics and clinical data
COAD = Chronic Obstructive Airway Disease.
* Includes Parkinson’s disease with psychosis.
** Includes obsessive–compulsive disorder (OCD) (n = 3).
*** Includes neurological and musculoskeletal disorders.
Presence of metabolic syndrome and associated parameters
Twenty-three (33.3%) participants met criteria for a diagnosis of metabolic syndrome in the previous year. Regarding individual metabolic parameters, 43 (62.3%) met the criteria for obesity, 36 (52.2%) fulfilled criteria or were receiving treatment for dyslipidaemia, 6 (8.7%) fulfilled criteria or were receiving treatment for hypertension and 10 (14.5%) fulfilled criteria for glucose intolerance or were receiving insulin treatment due to a diagnosis of diabetes mellitus.
Metabolic syndrome questionnaire
i) Awareness of metabolic syndrome
Of the 69 participants, 58 (84.1%) disagreed with the statement that they had heard of the term “metabolic syndrome” in the past. Seven participants “agreed” and two “strongly agreed” that they had heard of the term “metabolic syndrome”, with six (8.7%) participants agreeing that they understood what was meant by the term.
ii) Thoughts about own current physical health
Forty-seven (68.1%) participants agreed that they would describe their diet as healthy, with six (8.7%) disagreeing and 16 (23.2%) undecided. Seventeen (24.6%) participants in total reported consuming five portions of fruit or vegetables on a regular (often or always) basis (see Table 2). Fourteen (29.8%) of the 47 participants that agreed that they would describe their diet as healthy reported consuming five portions of fruit or vegetables on a regular basis. The mean consumption of fruit and vegetables reported by these 47 participants was 2.1 portions and 1.7 portions per day respectively and 20 (42.6%) of these participants reported at least weekly fast-food consumption. Regarding the six individuals that disagreed when asked if they would describe their diet as healthy, the mean consumption of fruit and vegetables reported was 0.3 portions daily respectively. Three of these six participants reported consuming fast-food at least twice weekly.
Table 2. Dietary and exercise habits
Thirty-five (50.7%) participants reported that they were moderately or extremely active (see Table 2). Thirty-eight (55.1%) participants reported that they engaged in an average of 2.5 hours or more of moderate-intensity activity on a weekly basis with 31 (81.6%) of these participants describing their activity levels as at least moderately active. Twenty-four (34.8%) participants reported that they were “smokers” and 21 (30.4%) reported that they were “ex-smokers” with 18 (85.7%) of these participants citing concerns for physical health and three (14.3%) citing mental health as the rationale for smoking cessation.
iii) Attitudes to physical health check-ups and appropriate frequency
Participants were asked about their attitudes towards individual components of physical health monitoring. The majority agreed that it was important to regularly check their bloods for diabetes mellitus (n = 50, 72.5%) and cholesterol levels (n = 55, 79.7%), to check their weight (n = 63, 91.3%) waist circumference (n = 63, 91.3%) and blood pressure (n = 66, 95.7%) (see Table 3). The most common response for how frequently physical health testing should occur was monthly (n = 46, 66.7%).
Table 3. Attitudes towards the importance of monitoring physical health parameters (Agree = strongly agree or agree, Disagree = strongly disagree or disagree)
There were no statistical differences between individuals who were interviewed in person compared to by phone consultation in relation to demographic or clinical data, awareness of metabolic syndrome, views of current physical health or in attitudes to physical health reviews.
Discussion
Summary of main findings
To our knowledge, this is the first study to evaluate awareness and understanding of “metabolic syndrome” in an exclusive cohort of participants prescribed clozapine. It is also the first study, to our knowledge, to evaluate attitudes towards physical health monitoring when prescribed clozapine in an Irish context. Several studies in Ireland and internationally have described the increased risk of metabolic syndrome and cardiovascular disease in individuals with schizophrenia (Vancampfort et al. Reference Vancampfort, Stubbs, Mitchell, De Hert, Wampers, Ward, Rosenbaum and Correll2015, Lydon et al. Reference Lydon, Vallely, Tummon, Maher, Sabri, McLoughlin, Liew, McDonald and Hallahan2021, Firth et al. Reference Firth, Siddiqi, Koyanagi, Siskind, Rosenbaum, Galletly, Allan, Caneo, Carney, Carvalho, Chatterton, Correll, Curtis, Gaughran, Heald, Hoare, Jackson, Kisely, Lovell, Maj, McGorry, Mihalopoulos, Myles, O’Donoghue, Pillinger, Sarris, Schuch, Shiers, Smith, Solmi, Suetani, Taylor, Teasdale, Thornicroft, Torous, Usherwood, Vancampfort, Veronese, Ward, Yung, Killackey and Stubbs2019). Analysing service user perspectives and attitudes towards metabolic syndrome and physical health monitoring highlights areas where interventions can potentially be introduced to reduce morbidity and premature mortality.
This study demonstrated a limited awareness and understanding of the term “metabolic syndrome” in service users attending a clozapine clinic. A recent qualitative study which included twelve participants with schizophrenia and eight participants with bipolar disorder noted a lack of awareness of the requirement for regular monitoring for metabolic syndrome or its components, with testing undertaken for example at times of physical ill-health rather than on a routine basis (Poojari et al. Reference Poojari, Mey, Khan, SHenoy, Pai, Shetty, Bhat, Bhandary, Acharya, Bose and Thunga2025). The components of metabolic syndrome, elevated blood pressure, obesity, lipid/cholesterol dysregulation and alterations in glucose metabolism, arguably feature more prominently in our lexicon and their perceived significance is shown in the vast majority of participants agreeing that it is important to monitor the associated physical parameters regularly (Table 3).
Over two-thirds of the participants in this study described their diet as healthy; however, less than a quarter (n = 17, 24.6%) of participants reported often or always meeting the World Health Organisation’s advice of consuming at least five portions (400g) of fruit and vegetables daily (WHO 2005). Although not the only aspect of healthy eating, this finding calls into question what the participants define as a healthy diet. With regards to physical activity, 55.1% of the participants in our study reported meeting the recommended 2.5 hours or more of moderate-intensity activity per week (HSE, Reference Hse2018). In addition to its well documented cardio-metabolic benefits, exercise has been shown to reduce clinical symptoms of schizophrenia (Dauwan et al. Reference Dauwan, Begemann, Heringa and Sommer2016). The dietary and exercise habits described in our study are consistent with those reported in a recent Australian study of 114 participants attending a community mental health team for the management of psychotic disorders, with similar figures reported for engagement in physical activity and dietary consumption of fruit and vegetables (Happell et al. Reference Happell, Platania-Phung, Furness, Scholz, Niyonsenga, Watkins, Curtis, Wang, Khanijou and Stanton2025). Our data is, however, in contrast with a previous Irish study involving individuals attending a rehabilitation and recovery mental health team with only 28% of participants (n = 29) in that study reporting at least 150 minutes of moderate-intensity exercise weekly (Matthews et al. Reference Matthews, Cowman, Brannigan, Sloan, Ward and Denieffe2018). It is possible that the participant cohort in our study had higher levels of functioning and less severe illness with only 11 study participants (16%) residing in a group home or hostel setting.
Approximately two-thirds of participants reported that they were “smokers” at one point. Of note, most individuals who no longer smoked cited physical health reasons as the rationale for smoking cessation. Findings in this study are consistent with the reported high prevalence rates of smoking in people with schizophrenia in Ireland and internationally, with various reasons for the phenomenon suggested (i.e. perceived positive effects on anxiety, attention, memory, negative affect and extra-pyramidal side effects) (Feeney & Hallahan, Reference Feeney and Hallahan2011, Dickerson et al. Reference Dickerson, Schroeder, Katsafanas, Khushalani, Origoni, Savage, Schweinfurth, Stallings, Sweeney and Yolken2018, Ding & Hu, Reference Ding, Hu and Faden2021). Smoking is significantly associated with metabolic syndrome with a stronger correlation with heavier smoking, and it is proposed that smoking may directly contribute to insulin resistance (Chiolero et al. Reference Chiolero, Faeh, Paccaud and Cornuz2008, Sun et al. Reference Sun, Liu, Ning and Barengo2012). It is important to monitor service users’ smoking status due to its physical health impact as well as its effect on clozapine levels, with smoking cessation often necessitating a reduction in the dose of clozapine prescribed (Feeney & Hallahan, Reference Feeney and Hallahan2011).
Strengths and limitations
Strengths of this study include the sample size of a defined service user population and the surveys were completed with the participant allowing any queries or uncertainties to be clarified. In terms of limitations, almost half of potential participants did not engage with this study so our study cohort may not be entirely representative of service users receiving clozapine treatment. It is possible that service users more open to interacting with the health service and health monitoring were more likely to engage with this study. The questionnaire utilised, predominately answered on a Likert scale, was not validated but was informed by international guidelines (WHO, 2005, HSE, Reference Hse2018), and subject to significant review prior to introduction. Thus, whilst the questionnaire was designed to elicit information in the multiple domains studied, it is associated with the potentially reduced reliability and comparability of using non-validated tools. Participants self-reported their dietary and exercise habits, which can lead to retrospective bias, however, completing the survey with a researcher (not involved in provision of clinical care to participants) who is in a position to describe and explain all questions and potential answers would potentially limit this. A risk of response bias must be acknowledged, with Firth et al highlighting over-reporting of activity levels by individuals with schizophrenia, although self-report data remained valuable (Reference Firth, Stubbs, Vancampfort, Schuch, Rosenbaum, Ward, Firth, Sarris and Yung2018b), and it is reassuring that our data is consistent with recent findings in a similar cohort (Happell et al. Reference Happell, Platania-Phung, Furness, Scholz, Niyonsenga, Watkins, Curtis, Wang, Khanijou and Stanton2025). Fruit and vegetable consumption guidelines and frequency of eating “fast food” were focused on in this study but are not the only components of a healthy diet. Approximate measures of impaired glucose tolerance (HbA1c) and central obesity (weight in kilograms or BMI) were utilised for some participants due to the lack of available data pertaining to fasting blood glucose levels or abdominal waist circumference.
Implications
Prescribing clozapine in Ireland requires monthly monitoring of service users’ full blood counts. This regular contact provides an ideal opportunity to monitor metabolic parameters as well as to facilitate learning for service users around physical health and the potential impact of lifestyle habits. Therapeutic relationships can provide a foundation to motivate service users towards healthier lifestyles and to work through challenges that may arise at an individual level. The feasibility and potential effectiveness of nutrition and exercise interventions for metabolic syndrome in persons with schizophrenia has been highlighted by systematic reviews (Gurusamy et al. Reference Gurusamy, Gandhi, Damodharan, Ganesan and Palaniappan2018, Korman et al. Reference Korman, Stanton, Vecchio, Chapman, Parker, Martland, Siskind and Firth2023, Yang et al. Reference Yang, Yuan, Zhang, Fu, Wang, Wang and Fang2024), with successful nurse-led interventions resulting in a reduced risk of developing metabolic syndrome in participants with mental illness described (Fraser et al. Reference Fraser, Brown, Whiteford and Burton2018, Fernández Guijarro et al. Reference Fernández Guijarro, Pomarol‐Clotet, Rubio Muñoz, Miguel García, Egea López, Fernández Guijarro, Castán Pérez and Rigol Cuadra2019, Çelik İnce & Partlak Günüşen, Reference Çelik İnce and Partlak Günüşen2021).
The need for early intervention for the prevention of metabolic syndrome has recently been emphasised in guidelines for the use of metformin in preventing antipsychotic-induced weight gain (Carolan et al. 2024). Our study highlights, in a cohort of service users prescribed clozapine, a limited awareness and understanding of the term metabolic syndrome and a differing view of what constitutes a healthy diet. The authors propose that early dietary and exercise interventions could be provided in clozapine clinics in Ireland.
Conclusion
In summary, this study found, in a cohort of service users prescribed clozapine in Ireland, a limited awareness and understanding of the medical term “metabolic syndrome”, although the majority of participants agreed that it was important to monitor weight, waist circumference, blood pressure, cholesterol and diabetes mellitus bloods. There was an inconsistency in the reported amount of fruit and vegetables being consumed by those that described their diet as healthy and the World Health Organization’s guidelines. The authors propose that early dietary and exercise interventions should be offered to this service user cohort.
Supplementary material
The supplementary material for this article can be found at https://doi.org/10.1017/ipm.2025.10117.
Acknowledgements
The authors would like to acknowledge the support from the clozapine clinic at University Hospital Galway and all study participants.
Author contributions
YF, CMcD and BH participated in the design of the study. YF engaged in data collection. JOD and YF engaged in study write-up. JOD, CMcD and BH engaged in critical review of the manuscript.
Funding statement
This research received no specific grant from any funding agency, commercial or not-for-profit sectors.
Competing interests
None.
Ethical standards
Ethical approval was obtained from the Galway University Hospitals Research Ethics Committee (C.A. 1462). The authors assert that all procedures contributing to this work comply with the ethical standards of the relevant national and institutional committee on human experimentation with the Helsinki Declaration of 1975, as revised in 2008.
Disclosure statement
The authors confirm that they have no conflict of interest to declare.
