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Addressing physical health in mental illness: the urgent need to translate evidence-based interventions into routine clinical practice

Published online by Cambridge University Press:  15 March 2021

B. O’Donoghue*
Affiliation:
Orygen, Parkville, VIC, Australia Centre for Youth Mental Health, University of Melbourne, Parkville, VIC, Australia Department of Psychiatry, St Vincents University Hospital, Dublin South East Mental Health Services, Dublin, Ireland
*
*Address for correspondence: Associate Professor B. O’Donoghue, Department of Psychiatry, Elm Mount Unit, St Vincent’s University Hospital, Elm Park, Dublin 4, Ireland. (Email: brian.odonoghue@orygen.org.au)
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Abstract

People affected by severe mental health disorders have a greatly reduced life expectancy compared to their non-affected peers. Cardiovascular disease is the main contributor to this early mortality, caused by higher rates of smoking, physical inactivity, unhealthy diet, sleep disturbance, excessive alcohol use or substance abuse and medication side effects. Therefore, we need to take a preventative approach and translate effective interventions for physical health into routine clinical practice. These interventions should be delivered across all stages of mental health disorders and could also have the added benefit of leading to improvements in mental health. Furthermore, we need to advocate to ensure that people affected by severe mental health disorders receive the appropriate medical assessments and treatments when indicated. This themed issue highlights that physical health is now an urgent priority for funding and development in mental health services. The widespread implementation of evidence-based interventions into routine clinical practice is an essential need for consideration by clinicians and policymakers.

Type
Editorial
Copyright
© The Author(s), 2021. Published by Cambridge University Press on behalf of The College of Psychiatrists of Ireland

Introduction

Over the last decade, there has been a paradigm shift in mental health services addressing the physical health of people affected by severe mental disorders. This response is appropriate as there is a wealth of research, amounting to nearly a 100 systematic review or meta-analyses, demonstrating that individuals affected by severe and enduring mental health disorders have more physical health comorbidities and a significantly reduced life expectancy compared to their peers (Firth et al. Reference Firth, Siddiqi, Koyanagi, Siskind, Rosenbaum and Galletly2019). Early studies revealed that it was those with a diagnosis of schizophrenia who died approximately 20 years younger (Hjorthøj et al. Reference Hjorthøj, Stürup, Mcgrath and Nordentoft2017). However, we now know that this earlier mortality is associated with all of the severe and enduring mental health disorders, including depression and personality disorders (Walker et al. Reference Walker, Mcgee and Druss2015). Tragically, this mortality gap is widening and has been described as ‘at best a failure to act on evidence and at worse a form of lethal discrimination’ (Thornicroft, Reference Thornicroft2013). Of late, there has been a shift in practice with mental health services beginning to assume some responsibility for addressing or advocating for the physical health of service users. However, while there is now sufficient knowledge that we need to address this issue, the most effective approach is not yet known. This themed issue on physical health aims to emphasise this critical issue and describe potential interventions to address the physical health of individuals affected by mental health disorders.

Translation of evidence-based interventions into routine clinical practice

This themed issue is timely, as, in the current circumstances of the COVID-19 pandemic, a significant proportion of the work of mental health services is being conducted via telehealth (Torous & Wykes, Reference Torous and Wykes2020). While telehealth has its advantages, there may be some drawbacks in addressing physical health, as individuals are attending the clinic in person less frequently. Therefore, there is a risk that the progress made by mental health services in addressing physical health over the last decade could inadvertently be reversed. Furthermore, people are less active due to restrictions of the pandemic and practices that previously occurred at clinics, such as metabolic monitoring, are now more challenging. There are many facets to this challenge; the first is that we need to identify interventions that are effective for either preventing or reversing the poorer physical health associated with severe mental health disorders. At this point, there is sufficient evidence supporting specific interventions that are detailed in resources such as the recent Lancet Commission: ‘A blueprint for protecting physical health in people with mental illness’ (Firth et al. Reference Firth, Siddiqi, Koyanagi, Siskind, Rosenbaum and Galletly2019) and also the ‘Maudsley Practice guidelines for Physical Health Conditions in Psychiatry’ (Taylor and Pillinger, Reference Taylor and Pillinger2020). The review on interventions to improve the physical health of people with a first episode of psychosis (FEP) by Fouhy et al. (Reference Fouhy, Cullen and O’connor2020) in this themed issue also highlights the limited, but effective interventions for this population (Fouhy et al. Reference Fouhy, Cullen and O’connor2020).

Therefore, this issue does not just focus on determining what works, but rather how we could translate these evidence-based interventions into routine clinical practice – which is likely to be the greatest challenge in addressing physical health in mental health disorders. For example, at Orygen, a youth mental health service in Melbourne, we established an exercise physiology service that provided treatment to young people with a FEP, those with an at-risk mental state, severe personality disorders or depression (Pearce et al. Reference Pearce, Foote, Brown and O’donoghue2020). The exercise physiologists provided individual and group programme sessions; however, we found that not all of the young people in need of the service were referred and there was suboptimal attendance and engagement for those who were referred (Pearce et al. Reference Pearce, Foote, Brown and O’donoghue2020). Hence, an urgent focus is needed to translate what we know works from controlled, well-funded research settings into routine practice. Matthews et al. (Reference Matthews, Cowman and Denieffe2018) argue that this translation could be achieved by integrating specialised exercise practitioners into mental health multidisciplinary teams and providing training on physical activity and sedentary behaviour interventions to mental health clinicians (Matthews et al. Reference Matthews, Cowman and Denieffe2018).

Physical health interventions across the continuum of mental health disorders

A staging model has been proposed in psychiatry in which the early stages are characterised by mild mental health symptoms to the more severe, relapsing disorders in the later stages (McGorry et al. Reference Mcgorry, Hickie, Yung, Pantelis and Jackson2006). It is proposed that treatments would differ at each point along this continuum, with interventions with lower risk–benefit ratios being provided in the early stages and more complex medical therapies in the later stages (Hickie et al. Reference Hickie, Scott and Mcgorry2013). Physical health interventions for people with mental health disorders map neatly onto this proposed staging model, as physical health interventions could have different roles across this continuum. In the early stages, a focus on modifiable risk factors could derive multiple benefits. First, interventions focusing early on smoking, physical inactivity, unhealthy diet, sleep disturbance, and excessive alcohol use or substance abuse could lead to a positive contribution to the long-term physical health of the individual. These interventions could also have a preventative effect, as all of the above-mentioned lifestyle factors can contribute to the onset of mental health disorders (Firth et al. Reference Firth, Solmi, Wootton, Vancampfort, Schuch and Hoare2020). Therefore, it is possible that if we intervene early with lifestyle interventions, then progression to a further stage on the continuum could be prevented. In the later parts of the staging model, while preventative measures are still necessary, more assertive and targeted approaches are required. An example of this is in the management of treatment-resistant schizophrenia, for which clozapine is the most effective treatment (Leucht et al. Reference Leucht, Cipriani, Spineli, Mavridis, Orey, Richter, Samara, Barbui, Engel, Geddes, Kissling, Stapf, Lassig, Salanti and Davis2013) but can have severe adverse effects on physical health (Tek et al. Reference Tek, Kucukgoncu, Guloksuz, Woods, Srihari and Annamalai2016). It is likely that lifestyle interventions alone would not be sufficient to counteract these adverse effects, and therefore, early use of interventions such as metformin are indicated (Siskind et al. Reference Siskind, Leung, Russell, Wysoczanski and Kisely2016). Targeting these lifestyle factors in those who are prescribed clozapine could derive multiple benefits, for example, employing strategies to reduce the prevalence of smoking (Siskind et al. Reference Siskind, Wu, Wong, Firth and Kisely2020), could result in achieving a therapeutic response with lower doses (Wagner et al. Reference Wagner, Mcmahon, Falkai, Hasan and Siskind2020), which in turn could lead to less metabolic side effects. Additionally, addressing obstructive sleep apnea, which is highly prevalent in this population, as demonstrated in this issue (Myles et al. Reference Myles, Myles, Vincent, Wittert, Adams, Chandratilleke, Liu, Mercer, Vakulin, Chai-Coetzer and Galletly2020), could potentially lead to better mental health and physical outcomes.

Effective reform will require attention to all stages of this continuum, with services such as the physical health monitoring service for people prescribed long-acting injectable medication described in this issue (Gill et al. Reference Gill, Mckenna, Mccauley and Gulzar2016; Lydon et al. Reference Lydon, Vallely, Tummon, Maher, Sabri, Mcloughlin, Liew, Mcdonald and Hallahan2020). However, it needs to be ensured that there are effective interventions in place for people identified in the screening process. To achieve this holistic care, a suite of physical health interventions would need to be available, including dietetics, physical activity programmes to reduce sedentary behaviour, tobacco smoking cessation and substance use interventions. Addressing just one factor in isolation is unlikely to have a substantial impact. For example, while there would be significant health benefits by increasing physical activity and improving diet, it would be unlikely to achieve a substantial change in life expectancy if the individual continued to smoke tobacco (Tam et al. Reference Tam, Warner and Meza2016). Hence, this calls for multiple, additional, resource-intensive interventions in mental health services that are already under-resourced. This leads to the next dilemma, who will provide these services?

Advocacy and the interface between psychiatry and other medical specialities

With the charge to address the physical health of people affected by mental health disorders, there has been less debate about who should deliver these services. Physical health is a broad term, and in addition to cardiovascular, respiratory and endocrine disorders, individuals with severe and enduring mental health disorders also have poorer sexual and reproductive health (Adan Sanchez et al. Reference Adan Sanchez, Mcmillan, Bhaduri, Pehlivan, Monson, Badcock, Thompson, Killackey, Chanen and O’donoghue2019) and dental health (Kisely, Reference Kisely2016). There is a limit to what is feasible and appropriate to be addressed by the mental health services based on resources, funding and expertise. Mental health services already take a collaborative approach to the care of people affected by mental health disorders by involving the affected individual, their caregivers, general practitioners and other health professionals. The same process should be taken in addressing physical health. A minimum standard could be determined by governing bodies and incorporated into the training of mental healthcare professionals. For anything beyond this, mental health services could negotiate with other health providers, such as general practitioners. The move towards establishing primary care centres in Ireland (Mental Health Reform, 2013), in which mental health and primary care are co-located, would make this a seamless process for the service user and their caregivers. The review by Fogarty et al. (Reference Fogarty, Mccombe, Brown, Van Amelsvoort, Clarke and Cullen2020) examines this issue and details the physical health issues of people affected by mental health disorders presenting to primary care (Fogarty et al. Reference Fogarty, Mccombe, Brown, Van Amelsvoort, Clarke and Cullen2020).

Advocacy is another required role for the mental health services to undertake in addressing the physical health of people affected by mental health disorders. People with severe mental health disorders are less likely to receive the indicated investigations and interventions and this is referred to as ‘diagnostic overshadowing’, in which there is a misattribution of physical symptoms to mental illness. It can occur most often in Emergency Departments, particularly those that are crowded and busy or when the patient presents with challenging behaviour (Shefer et al. Reference Shefer, Henderson, Howard, Murray and Thornicroft2014). However, it also occurs in medical and surgical specialities, for example, in Western Australia people with severe mental health disorders and ischemic heart disease were less likely to undergo life-saving revascularisation procedures compared to those without mental health disorders (Lawrence et al. Reference Lawrence, Hancock and Kisely2013). It is not surprising then that the mortality attributable to ischaemic heart disease had reduced in the general population in Western Australia, but this was not the case for people with severe mental health disorders (Lawrence et al. Reference Lawrence, Hancock and Kisely2013). Diagnostic overshadowing is less common in Emergency Departments that have liaison psychiatry services (Shefer et al. Reference Shefer, Henderson, Howard, Murray and Thornicroft2014), indicating that advocacy from mental health professionals is effective in addressing this practice. However, this stigma and discrimination against people with mental health disorders need to be addressed at a systemic level. Considering the high prevalence of mental health disorders in the general population and their high rates of physical health comorbidities, knowledge of mental health disorders should be a component of all medical and surgical specialities training. For some of these specialties, the only exposure to psychiatry will have been a relatively brief placement in medical training.

Mandating physical health monitoring

There are some intriguing puzzles relating to physical health. The early mortality outcomes are superior for individuals treated with clozapine compared to individuals treated with other antipsychotic medication (Tiihonen et al. Reference Tiihonen, Lonnqvist, Wahlbeck, Klaukka, Niskanen, Tanskanen and Haukka2009). This is hard to fathom, considering that clozapine is associated with the greatest risk for weight gain (Leucht et al. Reference Leucht, Cipriani, Spineli, Mavridis, Orey, Richter, Samara, Barbui, Engel, Geddes, Kissling, Stapf, Lassig, Salanti and Davis2013), diabetes in younger people (Lund et al. Reference Lund, Perry, Brooks and Arndt2001), myocarditis (Bellissima et al. Reference Bellissima, Tingle, Cicović, Alawami and Kenedi2018) and blood dyscrasia (Latif et al. Reference Latif, Jabbar and Kelly2011). Yet, the finding of superior morbidity and mortality has been replicated many times (Cho et al. Reference Cho, Hayes, Jewell, Kadra, Shetty, Maccabe and Downs2019; Wimberley et al. Reference Wimberley, Maccabe, Laursen, Sørensen, Astrup, Horsdal, Gasse and Støvring2017). One of the leading theories is that physical health monitoring is mandatory for the ongoing prescribing of the medication, thereby ensuring that individuals taking clozapine attend the mental health service monthly, thereby facilitating regular contact with their treating team. Pharmacists cannot dispense the prescribed clozapine until a neutrophil count is known, and this mechanism ensures 100% compliance. This procedure is accepted as being part of the process of prescribing clozapine. However, it needs to be asked why this process is only applied to a rare side effect (albeit potentially fatal) but not to the more common side effects, specifically metabolic side effects that strongly contribute to the early mortality in this population. Therefore, a drastic but potentially effective intervention could be to mandate regular anthropometric measurements, fasting glucose and lipids as a requirement for the ongoing prescription of all antipsychotic medication. This would ensure compliance with physical health screening and assist in the provision of interventions when indicated.

Ambitious and achievable targets

We need ambitious but achievable targets to bring about change. For example, the Healthy Active Lives (HeAL) declaration sets out a 5-year target for young people experiencing a FEP (International Physical Health in Youth (IPHYS) Working Group, 2013). It stipulates that young people with an FEP should have the same life expectancy as their non-affected peers, in that clinically significant weight gain should occur in less than 25% and that less than 30% smoke tobacco. It also sets out the target that more than half of people with an FEP engage in levels of physical activity appropriate for their age. These targets are ambitious and should be commended; however, they also need tiriso be supported by resources and training. To adequately manage the physical health of people with severe mental health disorders, clinicians will need to adapt their regular practice, which will require education and training. Many governing bodies have developed training modules on addressing physical health that have been incorporated into the training requirements for psychiatrists in some jurisdictions, such as Australia with the Royal Australian and New Zealand College of Psychiatrist (Lambert et al. Reference Lambert, Reavley, Jorm and Oakley Browne2017). The recent report on the ‘Physical Health of People with severe mental illness’ by the Mental Health Commission highlighted that specialist training in mental health should not be at the cost of treating the ‘whole’ patient (Finnerty, Reference Finnerty2019).

Conclusion

Despite early mortality in severe mental health disorders being established for decades, the gap in life expectancy between those with and without severe and enduring mental health disorders continues to widen (Lawrence et al. Reference Lawrence, Hancock and Kisely2013). The vast majority of this early mortality is attributable to preventable causes such as cardiovascular disease. Therefore, we need to take a preventative approach and translate effective interventions for physical health into routine clinical practice. Furthermore, we need to advocate to ensure that people affected by mental health disorders receive the appropriate medical assessments and treatments when indicated. Concurrently, we need to develop more effective, safe and acceptable interventions that can be delivered across the continuum of mental health disorders. This themed issue highlights that physical health is now an urgent priority for funding and development in mental health services and the widespread implementation of evidence-based interventions in routine clinical practice is an essential need for consideration by clinicians and policymakers.

Financial support

This article received no specific grant from any funding agency, commercial or not-for-profit sectors (or declare financial support if appropriate). Associate Professor Brian O’Donoghue is supported by the National Health and Medical Research Council (NHMRC) research fellowship.

Conflict of interest

The author has no conflict of interest to disclose.

Ethical standards

The author asserts 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. The author asserts that ethical approval was not required for the publication of this manuscript.

References

Adan Sanchez, AY, Mcmillan, E, Bhaduri, A, Pehlivan, N, Monson, K, Badcock, P, Thompson, K, Killackey, E, Chanen, A, O’donoghue, B (2019). High-risk sexual behaviour in young people with mental health disorders. Early Intervention in Psychiatry 13, 867873.CrossRefGoogle ScholarPubMed
Bellissima, BL, Tingle, MD, Cicović, A, Alawami, M, Kenedi, C (2018). A systematic review of clozapine-induced myocarditis. International Journal of Cardiology 259, 122129.CrossRefGoogle ScholarPubMed
Cho, J, Hayes, RD, Jewell, A, Kadra, G, Shetty, H, Maccabe, JH, Downs, J (2019) Clozapine and all-cause mortality in treatment-resistant schizophrenia: a historical cohort study. Acta Psychiatrica Scandinavica 139, 237247.Google ScholarPubMed
Finnerty, S (2019). Physical Health of People with Severe Mental Illness. Mental Health Commission: Ireland.Google Scholar
Firth, J, Siddiqi, N, Koyanagi, A, Siskind, D, Rosenbaum, S, Galletly, C, et al. (2019). The Lancet psychiatry commission: a blueprint for protecting physical health in people with mental illness. Lancet Psychiatry 6, 675712.CrossRefGoogle ScholarPubMed
Firth, J, Solmi, M, Wootton, RE, Vancampfort, D, Schuch, FB, Hoare, E, et al. (2020). A meta-review of “lifestyle psychiatry”: the role of exercise, smoking, diet and sleep in the prevention and treatment of mental disorders. World Psychiatry 19, 360380.CrossRefGoogle Scholar
Fogarty, F, Mccombe, G, Brown, K, Van Amelsvoort, T, Clarke, M, Cullen, W (2020). Physical health among patients with common mental health disorders in primary care in Europe: a scoping review. Irish Journal of Psychological Medicine, 117. Published online ahead of print.CrossRefGoogle ScholarPubMed
Fouhy, F, Cullen, W, O’connor, K (2020). Physical health interventions for patients who have experienced a first episode of psychosis: a narrative review. Irish Journal of Psychological Medicine, 114. Published online ahead of print.CrossRefGoogle ScholarPubMed
Gill, M, Mckenna, K, Mccauley, M, Gulzar, M (2016). Establishing a physical health monitoring service for patients on depot antipsychotic medication. Irish Journal of Psychological Medicine, 17. Published online ahead of print.CrossRefGoogle Scholar
Hickie, IB, Scott, J, Mcgorry, PD (2013). Clinical staging for mental disorders: a new development in diagnostic practice in mental health. Medical Journal of Australia 198, 461462.CrossRefGoogle ScholarPubMed
Hjorthøj, C, Stürup, AE, Mcgrath, JJ, Nordentoft, M (2017). Years of potential life lost and life expectancy in schizophrenia: a systematic review and meta-analysis. Lancet Psychiatry 4, 295301.CrossRefGoogle ScholarPubMed
International Physical Health in Youth (IPHYS) Working Group (2013). Healthy Active Lives (HeAL) Consensus Statement (https://www.iphys.org.au/). Accessed 25 January 2021.Google Scholar
Kisely, S (2016). No mental health without oral health. Canadian Journal of Psychiatry 61, 277282.CrossRefGoogle ScholarPubMed
Lambert, TJ, Reavley, NJ, Jorm, AF, Oakley Browne, MA (2017). Royal Australian and New Zealand college of psychiatrists expert consensus statement for the treatment, management and monitoring of the physical health of people with an enduring psychotic illness. Australian and New Zealand Journal of Psychiatry 51, 322337.CrossRefGoogle ScholarPubMed
Latif, Z, Jabbar, F, Kelly, BD (2011). Clozapine and blood dyscrasia. The Psychiatrist 35, 2729.CrossRefGoogle Scholar
Lawrence, D, Hancock, KJ, Kisely, S (2013). The gap in life expectancy from preventable physical illness in psychiatric patients in Western Australia: retrospective analysis of population based registers. BMJ 346, f2539.CrossRefGoogle ScholarPubMed
Leucht, S, Cipriani, A, Spineli, L, Mavridis, D, Orey, D, Richter, F, Samara, M, Barbui, C, Engel, RR, Geddes, JR, Kissling, W, Stapf, MP, Lassig, B, Salanti, G, Davis, JM (2013). Comparative efficacy and tolerability of 15 antipsychotic drugs in schizophrenia: a multiple-treatments meta-analysis. Lancet 382, 951962.CrossRefGoogle ScholarPubMed
Lund, BC, Perry, PJ, Brooks, JM, Arndt, S (2001). Clozapine use in patients with schizophrenia and the risk of diabetes, hyperlipidemia, and hypertension: a claims-based approach. Archives of General Psychiatry 58, 11721176.CrossRefGoogle ScholarPubMed
Lydon, A, Vallely, J, Tummon, A, Maher, S, Sabri, S, Mcloughlin, J, Liew, A, Mcdonald, C, Hallahan, B (2020). Routine screening and rates of metabolic syndrome in patients treated with clozapine and long-acting injectable antipsychotic medications: a cross-sectional study. Irish Journal of Psychological Medicine, 19. Published online ahead of print.CrossRefGoogle ScholarPubMed
Matthews, E, Cowman, M, Denieffe, S (2018). The next step: a strategic focus on physical activity and sedentary behaviour in Irish mental health care. Irish Journal of Psychological Medicine, 13. Published online ahead of print.CrossRefGoogle Scholar
Mcgorry, PD, Hickie, IB, Yung, AR, Pantelis, C, Jackson, HJ (2006). Clinical staging of psychiatric disorders: a heuristic framework for choosing earlier, safer and more effective interventions. Australian and New Zealand Journal of Psychiatry 40, 616622.CrossRefGoogle ScholarPubMed
Mental Health Reform (2013). Mental Health in Primary Care in Ireland: A briefing paper (www.mentalhealthreform.ie). Accessed 25 January 2021.Google Scholar
Myles, H, Myles, N, Vincent, AD, Wittert, G, Adams, R, Chandratilleke, M, Liu, D, Mercer, J, Vakulin, A, Chai-Coetzer, CL, Galletly, C (2020). Pilot cohort study of obstructive sleep apnoea in community-dwelling people with schizophrenia. Irish Journal of Psychological Medicine, 17. Published online ahead of print.CrossRefGoogle ScholarPubMed
Pearce, M, Foote, L, Brown, E, O’donoghue, B (2020). Evaluation of an exercise physiology service in a youth mental health service. Irish Journal of Psychological Medicine, 16. Published online ahead of print.CrossRefGoogle Scholar
Shefer, G, Henderson, C, Howard, LM, Murray, J, Thornicroft, G (2014). Diagnostic overshadowing and other challenges involved in the diagnostic process of patients with mental illness who present in emergency departments with physical symptoms--a qualitative study. PloS One 9, e111682e111682.CrossRefGoogle ScholarPubMed
Siskind, DJ, Leung, J, Russell, AW, Wysoczanski, D, Kisely, S (2016). Metformin for clozapine associated obesity: a systematic review and meta-analysis. PloS One 11, e0156208e0156208.CrossRefGoogle ScholarPubMed
Siskind, DJ, Wu, BT, Wong, TT, Firth, J, Kisely, S (2020). Pharmacological interventions for smoking cessation among people with schizophrenia spectrum disorders: a systematic review, meta-analysis, and network meta-analysis. Lancet Psychiatry 7, 762774.CrossRefGoogle ScholarPubMed
Tam, J, Warner, KE, Meza, R (2016). Smoking and the reduced life expectancy of individuals with serious mental illness. American Journal of Preventative Medicine 51, 958966.CrossRefGoogle ScholarPubMed
Taylor, DGF, Pillinger, T (2020). The Maudsley Practice Guidelines for Physical Health Conditions in Psychiatry. John Wiley & Sons Inc: West Sussex, UK.Google Scholar
Tek, C, Kucukgoncu, S, Guloksuz, S, Woods, SW, Srihari, VH, Annamalai, A (2016). Antipsychotic-induced weight gain in first-episode psychosis patients: a meta-analysis of differential effects of antipsychotic medications. Early Intervention in Psychiatry 10, 193202.CrossRefGoogle ScholarPubMed
Thornicroft, G (2013). Premature death among people with mental illness. BMJ 346, f2969.CrossRefGoogle ScholarPubMed
Tiihonen, J, Lonnqvist, J, Wahlbeck, K, Klaukka, T, Niskanen, L, Tanskanen, A, Haukka, J (2009). 11-year follow-up of mortality in patients with schizophrenia: a population-based cohort study (FIN11 study). Lancet 374, 620627.CrossRefGoogle Scholar
Torous, J, Wykes, T (2020). Opportunities from the coronavirus disease 2019 pandemic for transforming psychiatric care with telehealth. JAMA Psychiatry 77, 12051206.CrossRefGoogle Scholar
Wagner, E, Mcmahon, L, Falkai, P, Hasan, A, Siskind, D (2020). Impact of smoking behavior on clozapine blood levels - a systematic review and meta-analysis. Acta Psychiatrica Scandinavica 142, 456466.CrossRefGoogle Scholar
Walker, ER, Mcgee, RE, Druss, BG (2015). Mortality in mental disorders and global disease burden implications: a systematic review and meta-analysis. JAMA Psychiatry 72, 334341.CrossRefGoogle ScholarPubMed
Wimberley, T, Maccabe, JH, Laursen, TM, Sørensen, HJ, Astrup, A, Horsdal, HT, Gasse, C, Støvring, H (2017). Mortality and self-harm in association with clozapine in treatment-resistant schizophrenia. American Journal of Psychiatry 174, 990998.CrossRefGoogle ScholarPubMed