Introduction
Schizophrenia affects approximately 1% of the population worldwide, is associated with impaired quality of life and accounts for approximately 13 million disability-adjusted life-years worldwide (Wang et al. Reference Wang, Chan, Yang, Huang, Ho and Hwang2024). Schizophrenia is strongly associated with physical multi-morbidity with affected individuals approximately twice as likely to suffer from multiple chronic conditions (Pizzol et al. Reference Pizzol, Trott, Butler, Barnett, Ford, Neufeld, Ragnhildstveit, Parris, Underwood, Sánchez, Fossey, Brayne, Fernandez-Egea, Fond, Boyer, Shin, Pardhan and Smith2023), have a shortened life expectancy of approximately 10–20 years compared to the general population noted (Pizzol et al. Reference Pizzol, Trott, Butler, Barnett, Ford, Neufeld, Ragnhildstveit, Parris, Underwood, Sánchez, Fossey, Brayne, Fernandez-Egea, Fond, Boyer, Shin, Pardhan and Smith2023), with metabolic syndrome highly prevalent (Quek et al. Reference Quek, See, Yee, Rekhi, Ng, Tang and Lee2022). Lifestyle factors, negative symptoms, functional impairments and second-generation antipsychotic medications contribute to this increased cardiometabolic risk (Lydon et al. Reference Lydon, Vallely, Tummon, Maher, Sabri, McLoughlin, Liew, McDonald and Hallahan2021; Şenormancı et al. Reference Şenormancı, Korkmaz, Şenormancı, Uğur, Topsaç and Gültekin2021; Launders et al. Reference Launders, Jackson, Hayes, John, Stewart, Iveson, Bramon, Guthrie, Mercer and Osborn2025). Clozapine, a second-generation antipsychotic medication with established efficacy for treatment-resistant schizophrenia, significantly adversely impacts metabolic parameters and dysregulates adipose tissue homeostasis (Kristóf et al. Reference Kristóf, Doan-Xuan, Sárvári, Klusóczki, Fischer-Posovszky, Wabitsch, Bacso, Bai, Balajthy and Fésüs2016).
The importance of implementing adjunctive non-pharmacological interventions such as aerobic exercise has been investigated in recent years. Structured aerobic interventions have been associated with promising findings in relation to psychosis prevention, negative symptoms, cognitive function, quality of life, physical health parameters (hypertension, dyslipidaemia, obesity and glucose intolerance, and reduced all-cause mortality), with minimal adverse effects and cost-effectiveness demonstrated (Firth et al. Reference Firth, Rosenbaum, Stubbs, Gorczynski, Yung and Vancampfort2016; Launders et al. Reference Launders, Jackson, Hayes, John, Stewart, Iveson, Bramon, Guthrie, Mercer and Osborn2025; Vancampfort et al. Reference Vancampfort, Firth, Stubbs, Schuch, Rosenbaum, Hallgren, Deenik, Ward, Mugisha, Van Damme and Werneck2025). To date, formalised exercise programmes have not been integrated into routine care for most patients with treatment-resistant schizophrenia (Koorts et al. Reference Koorts, Eakin, Estabrooks, Timperio, Salmon and Bauman2018). Unsupervised exercise interventions (i.e. brisk walking) whilst more affordable and easier to deliver, typically produce smaller increases in physical activity (Firth et al. Reference Firth, Rosenbaum, Stubbs, Gorczynski, Yung and Vancampfort2016; Vancampfort et al. Reference Vancampfort, Firth, Schuch, Rosenbaum, Mugisha, Hallgren, Probst, Ward, Gaughran, De Hert, Carvalho and Stubbs2017). There is limited information pertaining to which factors influence individuals with treatment-resistant schizophrenia to engage in structured aerobic exercise, with some evidence for lower levels of functioning impacting on engagement rates (Schwaiger et al. Reference Schwaiger, Maurus, Lembeck, Papazova, Greska, Muenz, Sykorova, Thieme, Vogel, Mohnke, Huppertz, Roeh, Keller-Varady, Malchow, Walter, Wolfarth, Wölwer, Henkel, Hirjak, Schmitt, Hasan, Meyer-Lindenberg, Falkai and Roell2024).
Diets incorporating high proportions of saturated fats and low rates of fruit, vegetables and fibre which potentially can adversely impact both physical health indices and have been associated with a deleterious impact on symptomatology perhaps related to increased oxidative stress and systemic inflammation (Marx et al. Reference Marx, Lane, Hockey, Aslam, Berk, Walder, Borsini, Firth, Pariante, Berding, Cryan, Clarke, Craig, Su, Mischoulon, Gomez-Pinilla, Foster, Cani, Thuret, Staudacher, Sánchez-Villegas, Arshad, Akbaraly, O’Neil, Segasby and Jacka2021). Dietary interventions have noted in some but not all studies to benefit negative symptoms, cognitive deficits and physical health comorbidities in schizophrenia (Falkai et al. Reference Falkai, Maurus, Schmitt, Malchow, Schneider-Axmann, Röll, Papiol, Wobrock, Hasan and Keeser2021, Tompkins et al. Reference Tompkins, Piacenza, Harrington, Murphy, O’Donoghue, Lyne and Föcking2025).
The primary aim of this study, in a cohort of participants treated with clozapine, is to examine preferences for engagement in a structured exercise programme. Secondary aims include establishing which exercise type and setting are preferred by patients and which demographic and clinical factors are associated with a willingness to engage in a structured exercise programme. The study will additionally explore current dietary patterns and ascertain what factors impact or support individuals engaging in a healthier diet. By including qualitative data, a clearer understanding of motivating factors and potential barriers to changing exercise and dietary patterns will be attained. Consequently, this study will inform the development of interventions that address the physical health disparities in this population.
Methods
Design
A descriptive questionnaire utilising individual lifestyle risk factors and attitudes towards physical health checks and exercise preferences in the clinic was designed by DA, JOD, and BH. Several meetings were held to discuss the design of the questionnaire, which was based on a recent questionnaire utilised in the same patient cohort (O’Donoghue et al. Reference O’Donoghue, Fahy, Tummon, McDonald and Hallahan2025). It was additionally informed by reviewing the International Physical Activity Questionnaire (Craig et al. Reference Craig, Marshall, Sjostrom, Bauman, Booth, Ainsworth, Pratt, Ekelund, Yngve, Sallis and Oja2023) and consultation with authors of a randomised controlled trial of aerobic exercise in schizophrenia (Maurus et al. Reference Maurus, Roell, Lembeck, Papazova, Greska, Muenz, Wagner, Campana, Schwaiger, Schneider-Axmann, Rosenberger, Hellmich, Sykorova, Thieme, Vogel, Harder, Mohnke, Huppertz, Roeh, Keller-Varady, Malchow, Walter, Wolfarth, Wölwer, Henkel, Hirjak, Schmitt, Hasan, Meyer-Lindenberg and Falkai2023). Three open-ended questions regarding exercise, diet, and lifestyle change in the past five years were additionally included. Non-medical terminology was used to ensure clarity and comprehension for all interviewees (See Appendix 1). Participants were provided with guidance on how to complete the questionnaire and were able to seek advice from the researcher (D.A.) if they had any queries or concerns regarding any of the questions.
The 30-item Positive and Negative Symptom Scale (PANSS; Kay et al. Reference Kay, Fiszbein and Opler1987) was used to ascertain the participants’ symptomatology at time of interview. The Personal and Social Performance (PSP) Scale, adapted from the Social and Occupational Functioning Assessment Scale (SOFAS), was used to assess functioning levels in individuals (Morosini et al. Reference Morosini, Magliano, Brambilla, Ugolini and Pioli2000). The PSP is a 100-point single item rating scale divided into ten equal intervals with the rating based on four aspects of functioning (socially useful activities including work and study, personal and social relationships, self-care, and disturbing and aggressive behaviours).
Participants
Patients who had previously participated in a metabolic awareness study five years earlier and were still attending (O’Donoghue et al. Reference O’Donoghue, Fahy, Tummon, McDonald and Hallahan2025) the dedicated clozapine clinic at University hospital Galway were invited to participate in this study. Inclusion criteria required patients to (1) be on clozapine treatment, (2) be over 18 years of age, and (3) have capacity to participate in the study. Participants were excluded if they fulfilled criteria for an intellectual disability (intelligence quotient <70) or had a confirmed diagnosis of dementia. All responses were anonymised, and all data were stored securely and handled in accordance with the Data Protection Act, 2018. All participants provided written informed consent prior to completion in the initial study, with assent attained for engagement in this follow-up study. Ethical approval was obtained prior to study’s commencement by Galway University Hospital’s Research Ethics Committee (C.A. 1462).
Procedures
For individuals who provided written informed consent, clinical case notes were reviewed to attain basic demographic and clinical data, with this data supplemented via discussions with study participants and clozapine nursing staff. 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. Research interviews were conducted by DA and JOD in person (n = 41) or by phone (n = 2). between May 1st and June 21st, 2025.
Statistical analysis
Statistical analysis was performed using Statistical Package for Social Sciences 27.0 for Windows (SPSS Inc., IBM, New York, USA). Descriptive analyses of key demographic and clinical data were performed for categorical and continuous variables as appropriate. We utilised the student t-test for parametric data and the Chi-Square (χ2) or Fisher’s Exact test for non-parametric data as appropriate. Regression analyses were conducted to ascertain associations between a preference to engage in exercise and key clinical (PANSS, PSP, gender, and age) variables. The PANSS was re-coded, with each item being scored from 0-6 rather than 1–7 (score range 0–180 rather than 30–210) ensuring a “true zero score” enabling correct ratio and percentage calculations (Obermeier et al. Reference Obermeier, Mayr, Schennach-Wolff, Seemuller, Moller and Riedel2009). All statistical tests were two-sided, and the level for statistical significance was 0.05.
Free-text data were analysed utilising thematic analyses as outlined by Braun and Clarke (Reference Braun and Clarke2006) in relation to data pertaining to willingness to engage in exercise regimes and dietary habits. Thematic analysis was structured across six core phases (familiarisation with data, coding, generating themes, reviewing themes, defining themes, and write-up). Deductive coding was utilised based on the three open-ended questions provided. Two of the researchers (D.A., B.H.) independently coded all free-text comments. Subsequent meetings were held to discuss themes generated. Consensus from the researchers was attained (D.A, J.D., B.H.) in relation to the emergent themes.
Results
Demographic and clinical data
There were 69 participants in the initial study. Of these, three participants had died, and ten participants were no longer treated with clozapine. Of the 56 eligible study participants, three participants were acutely medically or psychiatrically unwell and unable to participate and ten refused to participate, and consequently, 43 individuals out of 56 eligible participants (76.8%) engaged in this study (Figure 1). Demographic and clinical data for these participants are presented in Table 1. Of note, 35 participants (81.4%) had a diagnosis of schizophrenia, the mean age of participants was 46.8 (SD = 9.4) years, and the mean daily clozapine dose was 330.2 mg (SD = 120.7).
Figure 1. Study flow of participants.
Table 1. Demographic and clinical data
PANSS = Positive and Negative Syndrome Scale; PSP = Personal and Social Performance.
Exercise and dietary patterns
Current exercise and dietary patterns for participants are detailed in Table 2. At the time of interview 19 participants (44.2%) perceived themselves as moderately and 29 participants (53.5%) perceived themselves as lightly active. Six participants (14.0%) reported always eating five portions of fruit or vegetables daily whilst 12 participants (27.9%) reported never meeting these recommended guidelines. Twenty-four participants (55.8%) reported never eating fast-food meals while one fast-food meal per week was reported in 12 participants (27.9%), and two fast food meals per week were reported in 7 participants (16.3%).
Table 2. Exercise and dietary patterns
Exercise preferences
Twenty-nine individuals (67.4%) stated that they would be willing to engage in an exercise programme (see Table 3). Of exercise activities suggested, brisk walking was identified as most popular (n = 25, 58.1%), followed by dancing (n = 12, 27.9%) and utilisation of a stationary bicycle (n = 11, 25.6%). There was no association between age (t = 0.25, p = 0.81), gender (χ2 = 2/38, p = 0.23), smoking status (p = 0.37), PANSS score (β = 0.003, p = 0.74) or PSP score (β = −0.001, p = 0.92) and a preference to engage in an exercise programme. Individuals who currently engaged in less exercise (inactive or lightly active) demonstrated a stronger preference for engagement in an exercise programme compared to individuals who engaged in at least moderate levels of exercise (χ2 = 6.38, p = 0.041).
Table 3. Preferences for engagement in and location of an exercise intervention
Includes football (n = 4), tennis (n = 2), aqua-aerobics, yoga and gym work (n = 1 each).
Qualitative data
Qualitative data related to both exercise and diet with 7 themes (Exercise = 5, Diet = 2) emerging.
Twenty-eight free text comments were provided relating to views on exercise (Box 1). The most common theme pertained to current self-motivation to engage in exercise (n = 8). A wish to engage in exercise was evident from concerns regarding physical appearance and weight motivating individuals to engage in exercise (n = 5), with physical health concerns both a motivator to engage in exercise but also a barrier for some due to their health precluding them from engaging in certain exercise (n = 5). Two themes reflected a reluctance to engage in aerobic exercise including environmental or practical issues (i.e. that made engagement in exercise more difficult (n = 6) including a discontinuation of some organised exercise programmes, and psychological barriers including amotivation, anergia or depressive symptoms impacting individuals’ ability to engage in an exercise programme (n = 4).
Box 1: Summary of thematic analysis of exercise behaviours
Two themes emerged from the 22 comments relating to diet and nutrition (Box 2) and included: (1) a willingness to change dietary intake for health reasons (weight loss, management of diabetes, and hypercholesterolaemia) including a willingness to eat specific foods that could ameliorate physical health including vegetables, reduce unhealthy dietary habits, and take vitamins or medications such as semaglutide, or reduce nicotine intake, (n = 21) and (2) amotivation impacting changing dietary pattern (n = 2).
Box 2: Summary of thematic analysis relating to diet and nutrition
Discussion
This study demonstrates that many individuals (approximately two-thirds) with treatment resistant schizophrenia/schizoaffective disorder are willing to engage in an aerobic exercise programme as part of their management plan, with different options acceptable. The most favoured option was brisk walking, with a preference for engaging in this programme outside of a group setting. Several group activities were also acceptable including walking or jogging groups, dancing, utilisation of a stationary bicycle and football. Few demographic and clinical factors were associated with engagement in an aerobic exercise programme; however, individuals who already engaged in at least moderate exercise stated a lower preference for engagement in an aerobic exercise regime programme. Reasons for engagement in exercise programmes and improved dietary intake included awareness of physical health and appearance benefits.
Almost half of the study participants engaged in at least moderate levels of exercise weekly, with some noting self-motivation, and others stating physical health or weight-related issues as motivational factors. Some of these participants described no need for further engagement in additional aerobic exercise activities (“I have good habits, now”). Given that a range of demographic and clinical variables including age, gender, diagnosis, smoking status, presence of metabolic syndrome, social and occupational functioning scores (PSP), and symptom severity ratings (PANSS) were not significantly associated with willingness to engage in an exercise intervention, this suggests that the inclusion of an aerobic exercise programme within Irish mental health services would have broad acceptability. In addition, this data suggests that individuals who currently engage in less exercise expressed a preference for the provision of a structured exercise programme. This finding is supported by qualitative data which for example noted that four of the six participants who reported environmental barriers impacting their current ability to engage in exercise programmes (discontinuation of previous exercise or soccer programmes) were engaged in less than 1.5 hours of activity per week.
Whilst a previous study noted that lower functioning (but no other clinical variables) was associated with reduced adherence with an aerobic exercise programme (Schwaiger et al. Reference Schwaiger, Maurus, Lembeck, Papazova, Greska, Muenz, Sykorova, Thieme, Vogel, Mohnke, Huppertz, Roeh, Keller-Varady, Malchow, Walter, Wolfarth, Wölwer, Henkel, Hirjak, Schmitt, Hasan, Meyer-Lindenberg, Falkai and Roell2024), this was not evident for all of the functioning scales utilised (Functional Remission of Schizophrenia but not Social and Occupational Functioning Scale or Global Assessment of Functioning) and previous data has shown no association with levels of overall functioning (Stubbs et al. Reference Stubbs, Vancampfort, Rosenbaum, Ward, Richards, Soundy, Veronese, Solmi and Schuch2016).
These findings provide a rationale for integrating structured aerobic activity programmes into the routine care of individuals with enduring mental health disorders (Mallorquí et al. Reference Mallorquí, Oliveira, Rios, Isla-Pera, Gil-Badenes, Amoretti, Bernardo, Vieta, Parellada, Garriga and García-Rizo2023). Such programmes should be designed to be simple, accessible, and flexible, offering participants choice (Vancampfort et al. Reference Vancampfort, Firth, Stubbs, Schuch, Rosenbaum, Hallgren, Deenik, Ward, Mugisha, Van Damme and Werneck2025), given that some activities are more suited to a group setting (i.e. dance Vancampfort et al. Reference Vancampfort, Firth, Stubbs, Schuch, Rosenbaum, Hallgren, Deenik, Ward, Mugisha, Van Damme and Werneck2025), whilst others can be either individual or group based (i.e. cycling, brisk walking). Given the European Medicines Agency recent regulatory revisions resulting in less frequent haematological monitoring after 18 weeks treatment with clozapine for patients in Ireland (EMA, 2025), an opportunity exists to utilise the time saved in haematological monitoring to offer these structured aerobic activity programmes.
The metabolic side effects of clozapine, particularly weight gain, emerged as a consistent concern across qualitative analyses and was noted to be a motivating factor for increased physical activity among this cohort, a finding consistent with other studies (Rojo et al. Reference Rojo, Gaspar, Silva, Risco, Arena, Cubillos-Robles and Jara2015; Silas et al. Reference Silas, Musso and Dolber2025). The awareness of- and preference to manage adverse sequelae of psychotropic medications including clozapine has previously been demonstrated with a similar previous cohort of participants demonstrating a high awareness of many of the components of metabolic syndrome and wish for regular physical health testing (O’Donoghue et al. Reference O’Donoghue, Fahy, Tummon, McDonald and Hallahan2025). Participants described a desire to change diet due to health-related concerns such as diabetes or weight management issues. Participants also alluded to a willingness to take supplements to improve their physical well-being including to improve cognition. Given emerging evidence for the benefit of glucagon-like-peptide-1 receptor agonists including semaglutide for weight management, this finding might be significant, particularly given recent evidence for weight loss secondary to semaglutide in a recent randomised placebo-controlled trial (Siskind et al. Reference Siskind, Baker, Arnautovska, Warren, Russell, DeMonte, Halstead, Iyer, Korman, McKeon, Medland, Parker, Stedman and Trott2025). Such therapeutic options could potentially be facilitated through clozapine clinics in the future given the time saving from reduced haematological monitoring.
This study has a number of limitations. The relatively small sample size suggests caution regarding the generalisability of the results, particularly to other cohorts of patients with major mental disorders and to findings of multivariate regression. The cross-sectional design limits the ability to evaluate whether intention and willingness is associated with the necessary follow-through which would lead to meaningful results (Ziliak and McCloskey Reference Ziliak and McCloskey2008). Additionally, social desirability bias relating to self-reported data on diet and physical activity may not accurately fully reflect true behaviour (Teh et al. Reference Teh, Abdin, P.V., Siva Kumar, Roystonn, Wang, Shafie, Chang, Jeyagurunathan, Vaingankar, Sum, Lee, van Dam and Subramaniam2023), albeit the addition of qualitative data supports the findings presented. The questionnaire utilised for lifestyle risk factors and attitudes towards physical health checks and exercise preferences is not validated.
Conclusion
Individuals with schizophrenia are willing to engage in aerobic exercise and dietary modification programmes. Tailored, interventions integrated into routine psychiatric care, such as clozapine clinics, may offer an effective strategy for improving both physical and mental health outcomes, with additional trials suggested to clearly evaluate potential benefits across functioning, quality of life, physical and mental health domains.
Acknowledgements
We wish to acknowledge and thank all participants for their time committed to this study and to the clozapine clinic at University hospital Galway for all their support and guidance.
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 attained prior to study commencement from the Galway University Hospitals Research Ethics Committee (C.A. 1,462). 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.
Appendix 1. Diet and Exercise Questionnaire
Please complete the following questions by circling the answer you feel is most appropriate to you.
Demographics
1. Your age in years:
2. Your gender
(3a) Are you a smoker?
If YES to the above:
(3b) How many cigarettes do you smoke per day?
If YES to the above two:
(3c) How many years have you been smoking for?
Thoughts about own current physical health
A “healthy diet” is a balanced diet containing the various different food groups including at least five portions of a variety of fruit and vegetables daily, high fibre starchy foods, some dairy or non-dairy alternatives and protein.
4. Would you describe your diet as healthy?
5. Do you eat 5 portions of fruit and vegetables daily?
6. On average, how many times do you eat fast food in a week?
“Exercise” is any physical activity that enhances or maintains physical fitness and overall health and wellness. Adults should do at least 2 and a half hours of moderate intensity activity a week. Examples of moderate activity include brisk walking, riding a bike, swimming leisurely, dancing and hiking.
7. How would you describe your current activity levels?
8. How much time, on average, do you spend participating in moderate activity a week?
9. Which of the following exercise regimes would you potentially be interested in
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• Stationary Bicycle Yes No
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• Jogging/Running Yes No
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• Brisk Walking Yes No
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• Dancing Yes No
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• Other __________________
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Your comments: Please provide your comments on the questions below – consider factors that might help or not-help you with making changes.
10. Have you changed your diet in the last 5 years and what are your views on changing your diet?
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11. Have you changed your exercise regime in the last 5 years and what are your views on changing your exercise patterns?
______________________________________________
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12. Have you changed your lifestyle in the last 5 years and what are your views on changing your lifestyle?
______________________________________________
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