The Lancet Psychiatry Commission

The Lancet Psychiatry Commission: a blueprint for protecting

physical health in people with mental illness
Joseph Firth, Najma Siddiqi*, Ai Koyanagi*, Dan Siskind*, Simon Rosenbaum*, Cherrie Galletly*, Stephanie Allan, Constanza Caneo,
Rebekah Carney, Andre F Carvalho, Mary Lou Chatterton, Christoph U Correll, Jackie Curtis, Fiona Gaughran, Adrian Heald, Erin Hoare,
Sarah E Jackson, Steve Kisely, Karina Lovell, Mario Maj, Patrick D McGorry, Cathrine Mihalopoulos, Hannah Myles, Brian O’Donoghue, Toby Pillinger,
Jerome Sarris, Felipe B Schuch, David Shiers, Lee Smith, Marco Solmi, Shuichi Suetani, Johanna Taylor, Scott B Teasdale, Graham Thornicroft,
John Torous, Tim Usherwood, Davy Vancampfort, Nicola Veronese, Philip B Ward, Alison R Yung, Eoin Killackey†, Brendon Stubbs†

Executive summary and cardiovascular diseases that is 1·4–2·0 times higher Lancet Psychiatry 2019;
Background than in the general population. Although cardio­ 6: 675–712

The poor physical health of people with mental illness is metabolic diseases have mostly been studied in patients Published Online
July 16, 2019
a multifaceted, transdiagnostic, and global problem. with severe mental illness (particularly psychotic
http://dx.doi.org/10.1016/
People with mental illness have an increased risk of disorders), the prevalence of cardiometabolic disease is S2215-0366(19)30132-4
physical disease, as well as reduced access to adequate also increased in individuals with a broad range of other See Comment pages 636 and
health care. As a result, physical health disparities are diagnoses, including substance use disorders and so- 638
observed across the entire spectrum of mental illnesses called common mental disorders (such as depression *Section lead authors
in low-income, middle-income, and high-income and anxiety). †Contributed equally
countries. The high rate of physical comorbidity, which NICM Health Research
often has poor clinical management, drastically reduces Part 2: Key modifiable factors in health-related Institute, Western Sydney
life expectancy for people with mental illness, and also behaviours and health services University, Westmead, NSW,
Australia (J Firth PhD,
increases the personal, social, and economic burden of Part 2 presents a hierarchical model of evidence synthesis
Prof J Sarris PhD); Division of
mental illness across the lifespan. to evaluate modifiable risk factors for physical diseases in Psychology and Mental Health,
This Commission summarises advances in under­ mental illness. Most top-tier evidence has identified School of Health Sciences
standing on the topic of physical health in people with that smoking, excessive alcohol consump­ tion, sleep (J Firth, R Carney PhD,
D Shiers MBChB,
mental illness, and presents clear directions for health disturbance, physical inactivity, and dietary risks are
Prof A R Yung MD), Division of
promotion, clinical care, and future research. The wide increased for a broad range of diagnoses, across various Diabetes, Endocrinology and
range and multifactorial nature of physical health economic settings, and from illness onset. Additionally, Gastroenterology (A Heald DM),
disparities across the range of mental health diagnoses parts 1 and 2 identify a scarcity of meta-research on the and Division of Nursing,
Midwifery and Social Work
generate a vast number of potential considerations. prevalence or risk factors of infectious diseases and (Prof K Lovell PhD), Faculty of
Therefore, rather than attempting to discuss all possible physical multi­ morbidity in mental illness. We also Biology, Medicine and Health,
combinations of physical and mental comorbidities highlight that increased attention on these areas will be University of Manchester,
individually, the aims of this Commission are to: particularly important in addressing the physical and Manchester, UK; Centre for
Youth Mental Health (J Firth,
(1) establish highly pertinent aspects of physical health- mental comorbidities observed in low-income and Prof P D McGorry MD,
related morbidity and mortality that have transdiagnostic middle-income settings. B O’Donoghue PhD,
applications; (2) highlight the common modifiable Prof A R Yung,
factors that drive disparities in physical health; Part 3: Interplay between psychiatric medications and Prof E Killackey DPsych), Orygen,
The National Centre of
(3) present actions and initiatives for health policy and physical health Excellence in Youth Mental
clinical services to address these issues; and (4) identify Part 3 examines the interactions between psychotropic Health (Prof P D McGorry,
promising areas for future research that could identify medications and physical health across a range of B O’Donoghue, Prof A R Yung,
novel solutions. These aims are addressed across the conditions. Antipsychotics remain the best evidence- Prof E Killackey), and
Department of Psychiatry
five parts of the Commission: in Parts 1 and 2 we based treatments for psychotic disorders and reduce (Prof J Sarris), University of
describe the scope, priorities, and key targets for mortality rates compared with no treatment, but they Melbourne, Melbourne, VIC,
physical health improvement across multiple mental have adverse effects on many aspects of physical health. Australia; Department of
illnesses; in Parts 3, 4, and 5, we highlight emerging Although drugs for depression have a less immediate Health Sciences, University of
York, Hull York Medical School
strategies and present recommen­dations for improving effect on cardiometabolic health than drugs for (N Siddiqi PhD, J Taylor PhD);
physical health out­comes in people with mental illness. psychosis per individual, drugs for depression are Bradford District Care NHS
prescribed much more commonly, and the number of Foundation Trust, Bradford, UK
(N Siddiqi); Research and
Part 1: Physical health disparities for people with prescriptions is increasing over time. Therefore, further
Development Unit,
mental illness research is required to establish the population Parc Sanitari Sant Joan de Déu,
Part 1 summarises the findings of almost 100 systematic burden of the cardiometabolic side-effects of drugs Universitat de Barcelona,
reviews and meta-analyses on the prevalence of physical for depression, particularly from long-term use. Part 3 Fundació Sant Joan de Déu,
Barcelona, Spain
comorbidities among people with mental illness. also discusses emerging pharmacological strategies
(A Koyanagi MD); Instituto de
Around 70% of the meta-research focuses on cardio­ for attenuating and managing physical health risks, and Salud Carlos III, Centro de
metabolic diseases, and consistently reports that mental provides recommendations for improving prescribing Investigación Biomédica en
illnesses are associated with a risk of obesity, diabetes, practices. Red de Salud Mental, Madrid,

www.thelancet.com/psychiatry Vol 6 August 2019 675

 The Lancet Psychiatry Commission

Spain (A Koyanagi); Institució Part 4: Multidisciplinary approaches to Part 1: Physical health disparities for people
Catalana de Recerca i Estudis multimorbidity with mental illness
Avançats, Barcelona, Spain
(A Koyanagi); Metro South
Part 4 discusses multidisciplinary lifestyle interventions Introduction
Addiction and Mental Health in mental health care. The Diabetes Prevention The premature mortality of people with mental illness
Service, Brisbane, QLD, Program (DPP) is an example of a gold-standard has been recognised by the medical community for more
Australia (D Siskind PhD, lifestyle intervention that has broadly been successful than half a century.1,2 Although premature mortality was
S Suetani MD); School of
Medicine (D Siskind,
in the general population. However, people with mental initially shown in patients with severe mental illnesses
Prof S Kisely DMedRes) and illness rarely have access to programmes based on the such as schizophrenia and bipolar disorder,3–5 there is
Queensland Brain Institute principles of the DPP, through either primary care or now evidence that individuals who have diagnoses across
(S Suetani), University of secondary care services. Based on the findings of large- the entire spectrum of mental disorders have a
Queensland, Brisbane, QLD,
Australia; School of Psychiatry,
scale clinical trials, we propose that future lifestyle substantially reduced life expectancy compared with the
Faculty of Medicine interventions in mental health care must adopt the core general population.3–11 Although suicide contributes to a
(S Rosenbaum PhD, principles of the DPP by partnering with appropriately consider­able proportion of these premature deaths (with
Prof J Curtis MBBS, trained physical health professionals, and by providing approxi­mately 17% of mortality in people with mental
S B Teasdale PhD,
Prof P B Ward PhD) and The
sufficient access to supervised exercise services. illness attributed to unnatural causes),12,13 the majority of
George Institute for Global Prevention is a key focus of the DPP. Similarly, lifestyle years of life lost in people with mental illness relate to
Health (Prof T Usherwood MD), interventions for people with mental illness should be poor physical health, specifically due to comorbid non-
University of New South Wales,
available pre-emptively to protect metabolic health communicable and infectious diseases.11,14–19 The
Sydney, NSW, Australia;
Ramsay Health Care Mental from the point of the first presentation of illness. consequent poor physical health out­ comes of people
Health, Adelaide, SA, Australia Priorities for future initiatives and research include with mental illness have been alluded to as a human
(Prof C Galletly MD); Northern translating the principles of the DPP into interventions rights issue,20 and the amount of research on this topic
Adelaide Local Health Network,
for people with mental illness across primary care, has increased substantially over the past two decades
Adelaide, SA, Australia
(Prof C Galletly); Institute of secondary services, and low-income and middle-income (appendix p 2).
Health and Wellbeing, settings, and using implementation science and cost- Despite the increasing amount of research in this area
University of Glasgow, effectiveness evaluations to develop a business case for and more general advancements in health care and
Glasgow, UK (S Allan MA);
integrating DPP-based interventions as the standard of medicine, the poor physical health outcomes (and the
Departamento de Psiquiatría,
Pontificia Universidad Católica care in mental health care. associated decrease in life expectancy) of people with
de Chile, Santiago, Chile mental illness have not improved.3,12,21 In fact, the number
(C Caneo MD); Youth Mental Part 5: Innovations in integrating physical and mental of years of life lost due to physical health conditions in
Health Research Unit (R Carney)
and Psychosis Research Unit
health care people with mental illness might be increasing.3,21–23 The
(D Shiers), Greater Manchester Part 5 focuses on the availability, content, and context of premature mortality of people with mental illness reflects
Mental Health NHS Foundation physical health care for people with mental illness. We a large number of health inequalities between people with
Trust, Manchester, UK; Centre summarise valuable new resources and guidelines from and without mental illness throughout the life course.
for Addiction and Mental
Health, Toronto, ON, Canada
national and international health bodies that aim to Although the psychiatric literature is largely unified on
(Prof A F Carvalho MD); address inequalities in both public health and clinical the consensus that physical comorbidities have a life-
Department of Psychiatry, settings. National health strategies urgently need to give shortening effect for people with mental illness, the
University of Toronto, Toronto, greater consideration to individuals with mental illness, prevalence and specific effects of the physical comorbidities
ON, Canada (Prof A F Carvalho);
Deakin Health Economics,
who are often left behind from population gains in public that can potentially affect individuals with diagnoses across
Institute for Health health. The development of integrated care models for the spectrum of mental disorders (not only severe mental
Transformation, Faculty of efficient management of physical and mental multi­ illness) have not yet been widely examined.
Health (M L Chatterton PharmD, morbidity is an important step forwards, particularly in
Prof C Mihalopoulos PhD) and
Food and Mood Centre
low-income and middle-income settings where health Comorbidity of mental and physical diseases:
(E Hoare PhD), Deakin inequalities for people with mental illness are greatest. a literature meta-review
University, Melbourne, VIC, Similarly, taking a syndemic approach to the interaction To provide an overview of the literature in this field, we
Australia; Donald and Barbara between physical and mental comorbidities might systematically identified all systematic reviews and
Zucker School of Medicine at
Hofstra/Northwell,
improve the implementation of customised health meta-analyses of chronic physical disorders in people
Hempstead, NY, USA interventions for a specific location or social setting. with common mental disorders, severe mental illnesses,
(Prof C U Correll MD); Continuing advances in digital health technologies also alcohol and substance use disorders, and various other
Department of Psychiatry, present new opportunities for addressing health mental health disorders, published between Jan 1, 2000,
Zucker Hillside Hospital, Glen
Oaks, NY, USA (Prof C U Correll);
inequalities on a global scale, although realising this and Oct 26, 2018. In particular, we sought to identify the
Department of Child and potential will be dependent on further rigorous top-tier evidence on the prevalence of chronic conditions
Adolescent Psychiatry, Charité research. The Commission concludes with a discussion in comparison with the general population (generally
Universitätsmedizin, Berlin,
on the accountabilities and responsibilities of defined as individuals without mental illness). Further
Germany (Prof C U Correll);
South London and Maudsley governments, health commissioners, health providers, details on our search strategy and selection criteria are
NHS Foundation Trust, and research funding bodies in implementing the in the appendix (pp 2–5). We considered this body of
London, UK (F Gaughran MD, recommendations of this Commission and protecting the meta-research and key recent reports from health-care
T Pillinger MRCP, B Stubbs PhD);
physical health of people with mental illness. and governmental bodies in developing the scope,

676 www.thelancet.com/psychiatry Vol 6 August 2019

 The Lancet Psychiatry Commission

Mental health treatment stage

Primary prevention Initial treatment Continuing care

Areas requiring further Global mental health initiatives Implement a physical health culture for Avoid diagnostic overshadowing
recognition The interactions between physical and mental mental health services The risk of physical symptoms being wrongly
disorders, and their shared risk factors, should be Regular screening is needed for physical disorders attributed to mental health disorders should be
clearly acknowledged and associated risk factors among patients with acknowledged, and the stigma that presents
mental illness, with evidence-based health barriers to health care for people with mental
promotion initiatives for staff and service users illness must be addressed

Local, national, and international health policy Improved use of medical investigations and
Health policy should address socioenvironmental treatments
factors that promote physical comorbidities in More training of health-care staff and wider access
mental illness, including the clustering of physical to screening and treatment (including
Actions for health and mental health risks in areas of social deprivation Improved referral pathways to specialised cardioprotective medications, bariatric surgery,
policy services services for managing comorbid substance use cancer screening) are required for people with
disorders chronic conditions

Equitable access to health care for low-income Integrated physical and mental health care
groups, geographical areas, and countries Integrated care should be available through primary care, from the first presentation of illness, and for those
with chronic conditions; developing sustainable models of integrated physical and mental health care will be
particularly important for low-income and middle-income settings

Promising areas for Dual prevention of physical and mental Provision of Diabetes Prevention Program-based Examine and reduce long-term side-effects of
future research comorbidities lifestyle interventions psychotropic medications
Large-scale interventions that target dual risk Lifestyle interventions should be implemented Longitudinal investigations and close clinical
factors for physical and mental health disorders in transdiagnostically from treatment initiation, to monitoring should be done to determine if and
at-risk groups (eg, obesity, smoking, inactivity, protect metabolic health; potential benefits for how side-effects of drugs (eg, SSRIs and
and poor diet) are required to reduce the prevalence improving mental health outcomes should also be second-generation antipsychotics) accumulate
of both examined over time, particularly during the transition from
childhood or adolescence into adulthood

Investigate use of digital technologies Continued investment in drug discovery

Explore the potential of digital technologies for Investigate psychotropics with minimal metabolic
checking health status and monitoring an side-effects, and develop adjunctive agents for
individual’s risk, and facilitating the delivery of reducing metabolic risk
lifestyle interventions

Figure 1: Strategies to protect physical health in people with mental illness

Strategies are applicable from the stage of mental illness indicated, and onwards. White boxes are areas that require further recognition. Grey boxes are actions for health policy and services. Orange boxes
are promising areas for future research. Boxes that have a gradient of two colours are included in two of these categories.

priorities, and recommendations of this Commission cardiac disease, hypertension, stroke, diabetes, metabolic Centre for Global Mental
(figure 1). syndrome, or obesity is around 40% higher than in the Health (Prof G Thornicroft PhD)
and Psychosis Studies
As detailed in table 1, since 2000, almost 100 systematic general population. Similarly, 16 reviews of cardiovascular (F Gaughran, T Pillinger,
reviews and meta-analyses have been published on the and metabolic health in patients with severe mental B Stubbs), Institute of
physical health comorbidities associated with mental illness14,54–58,77–80,91–95,100 showed clear evidence of an increase Psychiatry, Psychology and
illness. The findings from the most recent systematic in risk of 1·4–2·0 times across all cardiovascular and Neuroscience, King’s College
London, London, UK;
reviews and meta-analyses on the prevalence or risk of metabolic diseases examined. Although fewer studies Manchester Academic Health
physical illness for each category of mental illness are have been done for other mental disorders, the existing Science Centre, University of
shown in the appendix (pp 6–14). In common with reviews of anxiety disorders,46,76,87,98 substance use Manchester, Manchester, UK
another review,121 we found a shortage of evidence from disorders,81,96 attention-deficit hyperactivity disorder,101 (A Heald); Department of
Diabetes and Endocrinology,
low-income and middle-income countries. Most meta- and personality disorders104 consistently find evidence of Salford Royal Hospital, Salford,
research on the physical health of individuals with poor cardio­ metabolic health in patients with these UK (A Heald); Department of
mental disorders has focused on cardiovascular or diagnoses, with substantially higher rates of obesity, Behavioural Science and
metabolic diseases in high-income countries. Overall, diabetes, and metabolic syndrome than in the general Health, University College
London, London, UK
the available evidence shows that for individuals with population (appendix pp 6–14). The only inverse (S E Jackson PhD); Department
diagnoses across the entire spectrum of mental health relationship that has been identified between of Psychiatry, Dalhousie
disorders, the risk for cardiometabolic disease is cardiometabolic health and mental disorders is the University, Halifax, NS, Canada
(Prof S Kisely); Greater
increased by 1·4–2·0 times compared with individuals reduced incidence of diabetes in patients with anorexia
Manchester Mental Health NHS
without mental illness (appendix pp 6–14). For instance, nervosa (odds ratio [OR] 0·71) compared with those Foundation Trust, Manchester,
for patients with depression, the risk of developing without anorexia nervosa.82 However, because of the UK (Prof K Lovell); Department

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678
j.firth@westernsydney.edu.au
NSW 2145, Australia
Sydney University, Westmead,
Research Institute, Western
Dr Joseph Firth, NICM Health
Correspondence to:
(Prof P B Ward)
Liverpool, NSW, Australia
Applied Medical Research,
Unit, Ingham Institute of
and Schizophrenia Research
Padova, Italy (N Veronese MD);
Institute, Aging Branch,
Research Council, Neuroscience
(Prof D Vancampfort); National
Kortenberg, Belgium
Katholieke Universiteit Leuven,
University Psychiatric Centre,
(Prof D Vancampfort PhD);
Belgium
Universiteit Leuven, Leuven,
Sciences, Katholieke
Department of Rehabilitation
(Prof T Usherwood);
Westmead, NSW, Australia
School, University of Sydney,
Practice, Westmead Clinical
Department of General
Boston, MA, USA (J Torous MD);
Harvard Medical School,
Deaconess Medical Center,
Psychiatry, Beth Israel
S B Teasdale); Department of
Australia (Prof J Curtis,
Health District, Sydney, NSW,
South Eastern Sydney Local
the Body in Mind Program,
Australia (S Suetani); Keeping
Mental Health, Wacol, QLD,
Research, The Park Centre for
Centre for Mental Health
Italy (M Solmi MD); Queensland
University of Padua, Padua,
Padua Neuroscience Centre,
Neurosciences Department and
UK (L Smith PhD);
Ruskin University, Cambridge,
and Exercise Sciences, Anglia
Cambridge Centre for Sport
(Prof F B Schuch PhD);
Maria, Santa Maria, Brazil
Federal University of Santa
Sports Methods and Techniques,
(Prof J Sarris); Department of
Melbourne, VIC, Australia
The Melbourne Clinic,
London, UK (T Pillinger);
Imperial College London,
Sciences, Faculty of Medicine,
(T Pillinger); Institute of Clinical
Sciences, London, UK
London Institute of Medical
Medical Research Council
(H Myles MBBS, Prof C Galletly);
Adelaide, SA, Australia
University of Adelaide,
Discipline of Psychiatry,
Naples, Italy (Prof M Maj MD);
Campania Luigi Vanvitelli,
of Psychiatry, University of

Common mental disorders (48 reviews) Severe mental illnesses (30 reviews) Alcohol and substance Other mental illnesses (8 reviews) Mixed Total
use disorders mental
(6 reviews) illness
(7 reviews)
Depression Anxiety Mixed Schizophrenia Bipolar disorder Mixed severe Alcohol use Substance Attention- Autism Eating Personality
common mental illness disorder use deficit spectrum disorders disorders
mental disorder hyperactivity disorder
The Lancet Psychiatry Commission

disorder disorder
Number of 33 12 3 15* 8 7* 5 1 4 1 2 1 7 99
reviews
Non-communicable diseases
Asthma 2 reviews24,25 ·· ·· ·· 1 review26 ·· ·· ·· 1 review27 1 review28 ·· ·· ·· 5
Autoimmune ·· ·· ·· ·· ·· 1 review29 ·· ·· ·· ·· ·· ·· ·· 1
disorders
Cardiovascular 16 reviews30–45 6 reviews46–51 2 reviews52,53 2 reviews54,55 1 review56 3 reviews14,57,58 ·· ·· ·· ·· ·· ·· ·· 30
disease
Cancer 4 reviews59–62 ·· ·· 5 reviews63–67 ·· ·· ·· ·· ·· ·· ·· ·· 1 review68 10
Diabetes 7 reviews69–75 1 review76 ·· 2 reviews77,78 2 reviews79,80 1 review58 1 review81 ·· ·· ·· 1 review82 ·· 2 reviews83,84 17
Metabolic 2 reviews85,86 3 reviews87–89 1 review90 3 reviews78,91,92 3 reviews93–95 1 review58 1 review96 ·· ·· ·· ·· ·· 1 review97 15
syndrome
Obesity ·· 2 reviews98,99 ·· ·· 1 review100 ·· ·· ·· 3 reviews101–103 ·· ·· 1 review104 2 reviews97,105 9
106 107 108
Osteoporosis 1 review ·· ·· 1 review ·· ·· ·· ·· ·· ·· 1 review ·· ·· 3
or bone loss
Parkinson’s 1 review109 ·· ·· ·· ·· ·· ·· ·· ·· ·· ·· ·· ·· 1
disease
Rheumatoid ·· ·· ·· 1 review110 ·· 1 review29 ·· ·· ·· ·· ·· ·· ·· 2
arthritis
Infectious diseases
Hepatitis B ·· ·· ·· ·· ·· 3 reviews111–113 ·· ·· ·· ·· ·· ·· ·· 3
Hepatitis C ·· ·· ·· ·· ·· 3 reviews111–113 1 review114 1 review115 ·· ·· ·· ·· ·· 5
HIV ·· ·· ·· ·· ·· 3 reviews111–113 1 review116 ·· ·· ·· ·· ·· 1 review117 5
112
Syphilis ·· ·· ·· ·· ·· 1 review ·· ·· ·· ·· ·· ·· ·· 1
Tuberculosis ·· ·· ·· ·· ·· ·· 1 review118 ·· ·· ·· ·· ·· ·· 1
Other
Mixed ·· ·· ·· 2 reviews119,120 1 review95 1 review58 ·· ·· ·· ·· ·· ·· ·· 4
illnesses or
comorbidities
*Includes studies that examined several different mental illnesses.

Table 1: Map of systematic reviews and meta-analyses that have examined physical comorbidities across different mental illnesses

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 The Lancet Psychiatry Commission

Alcohol Tobacco use Physical activity Sedentary behaviour Poor diet Poor sleep
Major depression SR: around SR: patients are more likely MA: around 60–70% of MA: patients are ES: patients have ES: patients have significantly
30% of patients have or to smoke and be patients do not meet sedentary for 8·5 h significantly higher poorer continuity of sleep and
have had alcohol use dependent on nicotine, are physical activity per day127 food intake and reduced sleep depth
disorder124 less likely to quit, and are guidelines126,127 poorer diet quality compared with healthy
more likely to relapse125 than the general controls129
population128
Anxiety disorders ES: 17·9% of patients have MA: 41% increase in risk of ES: individuals with panic SR: inconsistent evidence Insufficient evidence MA: anxiety disorders129,134 and
alcohol dependence or regular smoking and 58% disorders, social phobia, for increased sedentary obsessive-compulsive
misuse130 increase in risk of nicotine and agoraphobia report time in people with disorder135 are associated with
dependence131 significantly less activity132 anxiety133 reduced sleep quality
Bipolar disorder MA: 1 in 3 patients have or MA: increased rates of MA: the majority of MA: patients are MA: patients consume MA: even between episodes,
have had alcohol use current smoking (higher patients meet physical sedentary for more than around 200 calories people with bipolar disorder
disorder136 than in patients with activity guidelines and are 10 h per day81,126 more than the general have increased sleep-wake
major depression but no different to the general population per day138 disturbance, similar to
lower than in patients with population81,126 patients with insomnia139
schizophrenia)137
Schizophrenia MA: 1 in 5 patients have or MA: significantly higher MA: the majority of MA: patients are MA: patients consume MA: patients have
have had alcohol use rates of current smoking, patients do not meet sedentary for around around 400 calories significantly reduced sleep
disorder140 heavy smoking, and physical activity 11 h per day142 more than the general time and quality of sleep129,134
nicotine dependence141 guidelines108,126 population per day138
First-episode MA: 27% of patients have MA: 58% of patients use MA: patients are less active Insufficient evidence Insufficient evidence MA: patients have
psychosis or have had alcohol use tobacco, which is a than individuals with significantly reduced sleep
disorder or alcohol significantly higher long-term schizophrenia108 time and quality of sleep134
dependence143 prevalence than in
matched controls144
Post-traumatic SR: increased prevalence of MA: patients are 22% MA: patients are 9% less Insufficient evidence MA: patients are 5% MA: significantly poorer
stress disorder comorbid alcohol misuse more likely to be current likely to be physically active less likely to have a continuity of sleep and
(10–61%) compared with smokers than the general than the general healthy diet than the reduced sleep depth
the general population145 population98 population98 general population98 compared with healthy
controls129
Results described as significant had p<0·05. Comparisons are with the general population unless otherwise stated. SR=systematic review of case-control, clinical, or epidemiological research. MA=meta-analysis
of multinational data. ES=large-scale epidemiological studies.

Table 2: Prevalence of behavioural risk factors across different mental health diagnoses

physically damaging behaviours that are inherent to the because the tendency to separate these two types of See Online for appendix
disorder, individuals with anorexia nervosa are at a much illness into different categories, despite their overlapping
higher risk for other health issues, such as a 12 times characteristics, could result in under­ estimations of the
greater incidence of osteoporosis,108 and one of the true burden of mental illness on a global level.122 A recent
highest rates of premature mortality across all mental meta-analysis has shown that for people with depression,
disorders (all-cause standardised mortality ratio 5·9, the risk of developing Parkinson’s disease is doubled
95% CI 4·2–8·3).12 Furthermore, individuals with other compared with people without depression,109 but the
eating disorders, such as bulimia, have a much higher relationships between other psychiatric and neurological
risk of diabetes (OR 3·45) than people without eating disorders have yet to be established.
disorders.82
The relationship between mental illnesses and cancer Gaps in the meta-research
risk is uncertain. Although some reviews have found that Our meta-research showed an absence of meta-analyses
mental illnesses are associated with a small increase in on chronic obstructive pulmonary disease (COPD) in
overall cancer risk,59 other reviews have found no people with mental disorders, although individual health
relationship, or a decreased cancer risk.63,68 The risk of database studies19,123 have found an increased prevalence
cancer associated with mental illness might vary for of COPD in people with severe mental illness.
different cancer types. For instance, whereas patients with The harmful effects of infectious diseases on the
common or severe mental illnesses have an increased risk physical health of people with mental disorders might
of lung cancer, the risk of colorectal cancer appears to be also be underestimated, because they have largely been
similar to (or even lower than) that in the general unexplored in mental health disorders other than severe
population.59,63 Further research is required to understand mental illnesses (table 2). The reviews that we identified
these relationships, but a possible explanation is that on infectious diseases in populations with severe mental
people with mental illness have a reduced life expectancy, illness found that the average prevalence (across multiple
resulting in a reduced lifetime rate of cancer in this group. countries) for hepatitis B infection, hepatitis C infection,
Another area requiring further investigation is the relation­ and HIV was 15·63%, 7·21%, and 7·59%, respectively,111
ship between psychiatric and neurological disorders, and the prevalence of syphilis was 1·1–7·6%.112 Within

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 The Lancet Psychiatry Commission

specific settings or countries, prevalence data highlight of these cases. Additionally, the development of cost-
that individuals with mental illness have an increased risk effective approaches that address the root causes of
of infectious disease compared with the general multimorbidity is needed to prevent long-term disability
population. For instance, in the USA, the prevalence of in people with mental illness.
both hepatitis B and hepatitis C infections in patients with
severe mental illness is around 20%, whereas the Further considerations
prevalence of these infectious diseases in the US Although the impact of physical comorbidities on the life
population is estimated to be 0·3% and 1·0%, expectancy of individuals with mental illnesses is well
respectively.146,147 Similarly, the median prevalence of HIV established,13,14 further research is needed to examine
among people with severe mental illness in the USA is whether the psychological distress associated with mental
1·8%, which is almost four times greater than the general illness is compounded by the additional burden of these
US population.146 In low-income and middle-income chronic conditions. For instance, in the general population,
settings, infectious diseases are a major cause of mortality diabetes is commonly associated with distress, which can
in people with severe mental illness. For example, in a have a considerable effect on the person’s quality of life
10-year follow-up study in Ethiopia,148 individuals with and their ability to manage their overall health.157 Diabetes-
severe mental illness died 30 years prematurely compared related distress also affects people with common mental
with the general population, and half of the deaths among disorders,157 severe mental illness,158 and substance use
individuals with severe mental illness were from disorders.159 The prevalence of obesity is considerably
infectious diseases. Further scientific and governmental increased across most classes of mental disorder compared
attention is required for infectious diseases among people with the general population (appendix pp 6–14). Weight
with mental illness in low-income and middle-income gain can be distressing and negatively affect an individual’s
settings, particularly given that rates of infection are quality of life and self-esteem, and might impede
highest in these settings, and inequalities between people treatment-seeking behaviour because an individual is
with and without mental illness are most pronounced.149 concerned about further weight gain.160 Similarly, obesity
Furthermore, despite the compelling evidence for can perpetuate lifestyle behaviours, such as social
increased risk of infectious diseases in adults with severe withdrawal161 and sedentary behaviour,126 that are
mental illness, the prevalence of infectious diseases in characteristic of many mental disorders, and are also key
other mental disorders, and the extent to which this risk factors for poor cardiometabolic health.162 Emerging
increased risk applies to young people with mental illness, evidence suggests that obesity and metabolic syndrome
is not well established. Future research should also aim to are independent predictors of relapse and rehospitalisation
identify the underlying factors resulting in an increased for those with severe mental illness.163,164 This relationship
rate of infectious diseases among people with mental could be explained by the inflammatory effects of
illnesses so that more appropriate and targeted solutions abdominal obesity; inflammation has also been associated
can be developed (as discussed in Part 2). with worse mental health165 and increased suicidality.166 In
Much of the published literature assessing physical addition to the personal burden, physical comorbidities in
health in mental illness to date has examined the people with mental illness result in an increased financial
prevalence of specific health outcomes or disorders in cost, the extent of which requires further research (panel 1).
isolation. The prevalence and specific effects of physical To address physical health inequalities in people with
multimorbidity (ie, the presence of more than one mental illness compared with those without mental illness,
chronic physical disorder) in people with mental illness we must focus on both reducing the prevalence of chronic
are not fully understood. Some large-scale, multinational health conditions, and lessening their effects across the
studies have shown that people with severe mental life course. In particular, cardiometabolic diseases are a
illness,123,150 common mental disorders,151,152 and substance relevant and transdiagnostic target for improving physical
use disorders18,153 are at a greatly increased risk of physical health outcomes across a broad spectrum of mental
multimorbidity from the point of onset of the mental illnesses. Although schizophrenia is typically associated
illness.154 The average age of onset of multimorbidity is with the greatest degree of cardio­vascular risk (partly due
younger in people with mental illness compared with the to the side-effects of drugs for psychosis), there is
general population.123,154 Multimorbidity greatly increases compelling evidence that the risk of obesity, metabolic
the personal and economic burden associated with syndrome, diabetes, and cardiometabolic disease is
chronic conditions, and reduces life expectancy compared similarly increased in other mental disorders, including
with a single morbidity.155,156 Urgent attention is required common mental disorders.46,76,83,85,87,97,98,175–177 Given the high
to address the onset and accumulation of physical prevalence of these mental disorders, developing strategies
multimorbidity, particularly in low-income and middle- for improving health outcomes that can be applied across
income settings, where physical multimorbidity is many different mental health diagnoses (including severe
increased among people with mental illness compared mental illness) could considerably reduce premature
with the general population,81,83,151 but services do not have mortality and the lifelong burden of poor physical health
the resources to deal with the burden and complexity for people with mental illness. The effects and prevalence

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of other non-communicable diseases and infectious

diseases in low-income, middle-income, and high-income Panel 1: Adding up the costs of physical comorbidities in
countries cannot be neglected. As such, under­standing people with mental illness
the epidemiology of mental and physical comorbidities Cost-of-illness studies, which assess the economic burden of
in low-income and middle-income countries,178 and a diagnosis or group of diagnoses, have found that people
developing evidence-based interventions that integrate with combined physical and psychiatric comorbidity have
mental and physical health care in these settings,179 is higher hospital costs, increased readmission rates, and higher
increasingly recognised as a major research priority for total health sector costs compared with people without
global health. The following parts of the Commission psychiatric diagnoses.163,167–171
discuss key modifiable factors that drive mental and
Although cost-of-illness studies are important for describing
physical health comorbidities, describe strategies for
economic burden, only economic evaluations can estimate
improving the management and prevention of these
the cost-effectiveness of interventions to support decision
conditions, and present directions for both immediate
making on the investment of limited health-care (and other
clinical action and future research to reduce physical
sector) resources. Economic evaluations are used to assess
health inequalities for people with mental illness (figure 1).
pharmaceuticals and health technologies in many countries.
Evidence regarding the cost-effectiveness of referral
Part 2: Key modifiable factors in health-related programmes and lifestyle interventions for people with
behaviours and health services mental illness and increased cardiovascular disease risk
Introduction
factors is mostly positive, but little evidence is available.172–174
Part 1 identified cardiometabolic diseases as a category
Further economic evaluations that collect cost and outcome
of physical comorbidities that is particularly pervasive
data, and that are done alongside clinical trials, will be needed
and has profound effects on patient wellbeing,
to provide convincing evidence of the economic benefits of
morbidity, and mortality, across many mental disorder
these programmes in people with mental health diagnoses.
diagnoses.46,76,81,83,85,87,96–98,157–159,175–177,180 In addition to the side-
effects of psychotropic medications (described in Part 3), Challenges to trial-based economic evaluations include
the reasons for increased cardiometabolic morbidity excessive respondent burden and respondent bias in collecting
and mortality in people with mental illness can be cost information, although these might be overcome by using
separated into patient-related factors and provider-level administrative data systems. Fragmentation of information
or system-level factors.121 and poor availability of data for some populations present
Lifestyle risk factors, such as smoking, poor diet, and additional challenges. Trial-based evaluations, which often use
inactivity, are modifiable, patient-related factors that intermediate efficacy endpoints (eg, LDL cholesterol levels),
are known to be associated with cardiometabolic will be an important source of data for modelled economic
disease,108,128,138,141 as well as affecting many other aspects of evaluations. Modelled evaluations will be crucial to establish
physical health.46,76,81,83,85,87,96–98,175–177 However, the extent to the long-term cost-savings and improvements in outcomes
which lifestyle risk factors in patients with various (eg, quality of life and mortality) through the avoidance of
mental disorders differ from the general population is future health consequences, such as metabolic syndrome and
not fully established. As a result, current lifestyle cardiovascular disease events. As this area of research develops,
interventions for people with mental illness could be both trial-based and modelled economic evaluations will need
imprecise, or could focus too much on one behavioural to adhere to published methodology standards, including
modification at the expense of other important risk presenting health-care and societal perspectives to assist
factors (eg, increasing physical exercise without policy makers.
considering the impact of diet, or focusing on smoking
over alcohol intake). Lifestyle risk factors across various diagnoses
We applied a systematic hierarchical approach Although the initial aim of our hierarchical evidence
(appendix pp 15, 16) to identify top-tier evidence on synthesis was to determine key lifestyle risk factors that
lifestyle risk factors for non-communicable diseases in are associated with individual mental disorders, most of
people with mental illness. We focused on behavioural the published literature showed that all psychiatric
risk factors in affective and psychotic disorders, rather diagnoses are associated with a wide spectrum of lifestyle
than on mental health illnesses that are characterised risk factors (table 2). People with mental illness tend to
by physically damaging behaviours, such as eating have more unhealthy lifestyles compared with the general
disorders and substance or alcohol use disorders (in population, and among people with mental illness, those
which the greatest behavioural risks to physical health with schizophrenia have a particularly high risk of
are the behaviours that define the conditions). Table 2 smoking, sedentary behaviour, and poor diet.128,137,138
summarises findings from meta-analyses, systematic Socioeconomic factors could partly mediate this trend,
reviews, and population-scale studies, published since because the incidence of schizophrenia is higher in low-
2000, on lifestyle risk factors in various mental health income communities,181 and such communities also have
populations. higher rates of behavioural risk factors compared with

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high-income communities.182 However, lifestyle risk

35 factors are still greater in patients with schizophrenia
than those with other mental health disorders, even when
controlling for socioeconomic factors. For instance, a
30
population-scale study from 2018 that used data from the
Increase in daily intake compared with control group (g)

UK Biobank128 found that individuals with severe mental

25 illness ate more obesogenic food than the general
population, particularly those with schizophrenia
(figure 2), and the differences in diet persisted after
20 adjusting for social deprivation and education.128 The use
of second-generation antipsychotics (SGAs) could
contribute to changes in diet, because trials in healthy
15
volunteers found that SGAs such as olanzapine can
reduce satiety, increase appetite183 and lethargy, and have
10 sedative effects.184–186 Although some SGAs, such as
olanzapine, have the most obvious cardiometabolic side-
effects, other more widely prescribed psychotropic
5 medications also have cardiometabolic side-effects that
accumulate over time. Thus, early intervention strategies
for managing lifestyle and cardiometabolic risk for
0
patients treated with psychotropic medications are
Major depressive
disorder*

Major depressive
disorder*
Major depressive
disorder*

Schizophrenia*

Schizophrenia*

Schizophrenia*
Bipolar disorder†

Bipolar disorder*

Bipolar disorder*

important for preventing cardiometabolic diseases from

arising (panel 2) The side-effects of SGAs and other
psychotropic medications (such as drugs for depression)
are discussed further in Part 3.
Protein Carbohydrates Sugars
Lifestyle risk factors in low-income and middle-income
10
settings
Although most of the data presented in table 2 are from
9
high-income countries, similar trends have been found
in low-income and middle-income countries.137,141,194–199 For
Increase in daily intake compared with control group (g)

8
instance, data from the WHO Study on Global Ageing
7 and Adult Health and the WHO World Health Survey
show that individuals with depression in low-income
6 and middle-income countries are more likely to
smoke (OR 1·41),194 to not meet physical activity
5 guidelines (OR 1·42),195 and to have sedentary behaviour
for 8 h or more per day (OR 1·94)196 than individuals
4 without depression. Similarly, low levels of physical
activity are found in individuals with anxiety and
3 psychotic disorders in low-income and middle-income
countries.137,141,197–199 Despite the differences in sociocultural
2
factors in low-income and middle-income countries
compared with high-income countries, people with
1
mental illness in both settings have more lifestyle risk
factors compared with the general population. In low-
0
income and middle-income countries, there are new
Major depressive
disorder*
Major depressive
disorder†

Major depressive
disorder*
Schizophrenia*

Schizophrenia*

Schizophrenia*
Bipolar disorder†
Bipolar disorder*

Bipolar disorder*

challenges to maintaining a healthy lifestyle caused by

the spread of fast-food restaurants, new technologies
that allow for reduced physical inactivity, and tobacco
promotion and legislation.200–202 Because lifestyle risk
Fibre Fats (all) Saturated fats factors, such as physical inactivity and poor diet, are
elevated in people with mental illness (table 2), further
Figure 2: Dietary intake by food group in patients with major depressive disorder (n=14 619), bipolar disorder efforts are needed to develop lifestyle interventions that
(n=952), and schizophrenia (n=262)
Bar heights represent the age-adjusted and sex-adjusted mean differences. Error bars represent 95% CIs of adjusted address these factors appropriately for those with mental
means. Data are based on the UK Biobank study and reproduced from Firth and colleagues.128 *p<0·05 compared with illness living in low-income and middle-income settings
healthy controls. †p<0·001 compared with healthy controls. (see Part 5).

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In addition to non-communicable diseases, other

behavioural risk factors, such as intravenous drug use Panel 2: Why wait for weight? Tipping the scales towards prevention
and high-risk sexual behaviours, are also over-represented Clinical guidelines for metabolic screening upon initiation or continuation of
in people with severe mental illness in low-income, second-generation antipsychotics recommend that blood pressure, body-mass index,
middle-income, and high-income settings (see Part 1), blood glucose, and lipid profile should be checked at least every 6 months.187–189 This is a
and can lead to infectious disease. Most available data are positive example of considering physical health outcomes for people with severe mental
for adults with severe mental illness, so the prevalence in illness. However, a large body of research in the general population has shown that
other age groups and for other diagnoses might be preventing conditions such as obesity and metabolic syndrome from arising is
underestimated. For instance, a recent meta-analysis203 of considerably more efficient than attempting to reverse their long-term consequences.190
3029 adolescents with a range of psychiatric diagnoses Thus, proactive lifestyle interventions in mental illness might not have their maximal
showed a 15% (95% CI 3–50) lifetime prevalence of effect if the interventions are only provided after large changes in biological or clinical
sexually transmitted illnesses, and found that 40% markers of adverse metabolic health are found during screening.
(95% CI 23–78) of the adolescents had shown high-risk
Individuals with first-episode psychosis are at considerable lifestyle risk from illness onset
sexual behaviour during their most recent sexual
(table 2), because they tend to be less physically active and have a higher rate of alcohol
encounter. Furthermore, recent alcohol use increased the
use disorders than those with long-term schizophrenia, and also have nutrient deficits
likelihood of having unprotected sex (OR 1·66, 95% CI
and a high rate of smoking (around 60% for both first-episode psychosis and
1·09–2·52).203 The interactions between risk factors for
schizophrenia, which is much higher than in the general population). Many other
non-communicable diseases and infectious diseases
behavioural risk factors also seem to precede, rather than accompany, the onset of
should not be overlooked, and suggest that screening for
psychotic disorders,191 and metabolic disturbance might be present from illness onset.192
multiple lifestyle factors, rather than single factors or
biological markers alone, will be the most efficient Although treatment with second-generation antipsychotics (SGAs) can be important for
method for improving health outcomes for people with stabilising mental health, taking these drugs can further increase metabolic risk (see Part 3).
mental illness. Given the high likelihood of physical health deterioration while taking SGAs, clinicians who
prescribe them to patients have a duty of care to ensure that the patients are given access to
Interventions for multiple lifestyle risk factors in mental evidence-based lifestyle interventions (as detailed in Part 4) from the start of treatment.
illness Lifestyle interventions should be made available even to those with intact metabolic health.
In summary, although our evidence synthesis process Although health screening should continue, more timely and effective strategies for
aimed to identify key behavioural risk factors for improving health outcomes will require intervening on the basis of lifestyle plus
specific mental disorders, the evidence suggests that pharmacological risk, rather than waiting for visible weight gain or metabolic dysfunction
simultaneously considering multiple lifestyle factors is to happen.193
more appropriate in understanding and managing risk
factors across all mental health diagnoses. However,
such transdiagnostic, multifactorial approaches are not physical health information than that which is typically
widely reflected in the published literature, which provided from screening for biological markers, because
generally focuses on specific factors for individual patients will be informed of specific lifestyle changes
disorders. Furthermore, no suitable tools are available for they could make to protect their physical health. Self-
clinicians to comprehensively assess lifestyle factors as report questionnaires are often burdensome and
part of standard care. The sole use of biological markers inaccurate, reducing their suitability for capturing
for physical health assessment (such as >7% increase in lifestyle factors in people with mental illness.205 Thus, a
bodyweight, high blood pressure, and an abnormal lipid priority for future research is to examine if digital
profile) could mean that interventions are applied only technologies (including smartphones and wearable
when it is too late to protect metabolic health or pre-empt technologies) could provide feasible and accurate
obesity (panel 2). Clinical guidelines are increasingly methods of broad lifestyle assessment.205,206
recommending that assessments of diet, physical activity, In addition, more efficient care pathways are needed to
and health risk behaviours are done alongside assess­ help people with mental illness minimise behavioural
ments of anthropomorphic parameters and blood risk factors (see Part 4). For instance, multidisciplinary
markers of metabolic status,204 to more accurately assess referral pathways (available through both primary and
current physical health and future risk. secondary care) could provide access to specialised
To comprehensively promote the physical health of physical activity, smoking cessation, dietetics, and other
people with mental illness, a positive first step would be allied health services, depending on the individual’s
developing quick and widely applicable tools for lifestyle specific behavioural profile and health goals. The
screening. These tools could be used across different dissemination of risk behaviour interventions in low-
diagnoses, settings, and services, to assess a range of income and middle-income countries is an urgent
behavioural risk factors (eg, exercise, diet, substance use, challenge, because individuals with mental illness in
and sleep) at once, and thus identify key drivers of poor these countries are disproportionately affected by an
physical health on a case-by-case basis. A comprehensive increased risk for infectious diseases and non-
lifestyle assessment would give patients more actionable communicable diseases.

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Health provider-level and system-level factors psychiatric disorder, resulting in missed diagnoses
Lifestyle-related factors are unlikely to be the only (sometimes known as diagnostic overshadowing).224,225
explanations for poor physical health outcomes in In addition, people with mental illness can have
people with mental illness.121 For severe mental illness difficulties with reporting medical problems,
in particular, mortality remains high even after distinguishing physical symptoms from the symptoms
adjusting for behavioural risk factors such as smoking, of mental illness, and engaging with health services (ie,
physical activity, and body-mass index.207 Increasingly, attending follow-up appointments), particularly if the
evidence suggests that the poor physical health services are non-inclusive, or perceived as non-
outcomes of people with mental illness are partly inclusive, of people with mental illness.224,226
driven by differences in the availability and quality of Physicians might be reluctant to offer some medical
health care that they receive. For instance, people with procedures to people with mental illness because of the
severe mental illness are less able to access adequate ensuing psychological stress, difficulties with obtaining
health care than the general population. In the USA, informed consent or compliance with postoperative
people with severe mental illness are twice as likely as care, or contraindications, such as substance misuse and
those without mental disorders to have been denied smoking.226 However, contraindications to specialised
medical insurance because of a pre-existing condition.208 interventions, such as smoking or problems with
These disparities exist at all levels of health services. In informed consent, are not relevant to the prescription of
primary care, people with severe mental illness are less vascular drugs, such as angiotensin-converting enzyme
likely to have a physical examination (eg, weight and inhibitors, β blockers, or statins, that are known to
blood pressure),209 or to be assessed and treated for reduce morbidity and mortality.227 Further­more, people
hyper­ lipidaemia, than people without mental with schizophrenia are as adherent to diabetes
illness.210,211 People with mental illness also have more medication as the general population.228 Access to
emergency department visits and more avoidable secondary health care for people with mental illness
admissions to hospital for physical conditions that with might be restricted by financial costs, fragmen­tation of
appropriate primary care should not require inpatient care, and social stigma.224,226,229 Although health-care
treatment.212 Patients with a range of psychiatric providers should recognise that challenging behaviour
diagnoses, including depression, anxiety, substance use can be a symptom of illness, evidence shows that some
disorder, and severe mental illness, have reduced access health-care providers have stigmatised views towards
to oral health care.213,214 people with mental illness.224,225 Nonetheless, health
In secondary health services, physical health might services should routinely offer health screening and
also be poorly managed for people with mental illness.215 lifestyle interventions for people with psychiatric
In particular, people with mental illness are less likely disorders, in the same way as for patients with chronic
to receive medical or surgical interventions that are physical conditions.230
commonly given in the general population. For In conclusion, people with mental illness are likely to
example, people who have had prior contact with receive a poorer standard of health care compared with
mental health services are less likely to receive cardiac people without mental illness who have the same
catheterisations and coronary artery bypass grafting physical health problems. To address this discrepancy,
than people who have no prior contact, which changes need to be made in the training of health
contributes to the higher mortality for circulatory providers and to the overall health system (see Part 5).
disease among people with a history of mental Greater integration of physical and mental health care
illness.216–218 People with mental illness are also less in primary care settings is a key recommendation for
likely to receive appropriate medications, such as β improving the management of physical comorbidities
blockers and statins, at discharge after myocardial in people with mental illness. Mental health clinicians
infarction.219 The incidence of many cancer types should be wary of attributing emerging somatic
(including common types, such as breast, colorectal, symptoms solely to an underlying mental illness, and
and prostate cancer and melanoma) among patients refresher training on the detection, management,
with psychiatric illness is only slightly higher than that and prevention of chronic medical conditions needs to
of the general population (see Part 1), but mortality is be available to mental health staff.229 Furthermore,
markedly higher.220,221 Disparities at the health-service developing clinical tools for comprehensive lifestyle
level are thought to be responsible for increased cancer assessment, and improving referral pathways
mortality, because people with mental illness are less to targeted interventions, will enable practitioners to
likely to be offered cancer screening,222 have a reduced identify and manage cardiometabolic risk factors in a
likelihood of surgery for all types of cancer, and wait timely manner. At the service level, screening
longer for surgery.223 procedures need to be improved to support prevention
A possible explanation for disparities in care for initiatives, alongside investment in the integration
people with mental illness is that clinicians attribute of physical health within mental health services, and
emerging somatic symptoms to the patient’s underlying vice versa.

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Part 3: Interplay between psychiatric block dopamine in the tuberoinfundibular pathway,

medications and physical health leading to reduced inhibition of prolactin synthesis and
Introduction secretion. Hyperprolactinaemia is most commonly found
As discussed in Part 1, a broad range of psychiatric with first-generation antipsychotics, as well as risperidone,
diagnoses are associated with high comorbidity for paliperidone, and amisulpride.247 Hyperprolactinaemia can
physical conditions (particularly cardiometabolic diseases). be asymptomatic, or can lead to complications, such as
Although lifestyle risk factors for chronic illness seem to menstrual disturbance and sexual dysfunction (including
be consistent across a wide range of mental illnesses reduced libido, erectile dysfunction, vaginal dryness, and
(Part 2), the physical health risks associated with individual orgasmic dysfunction248) in the short-term,247 and
mental health diagnoses are modified by the types of osteopenia in the long-term.249
psychotropic medications that are given to treat each
condition. In this section, we present research on the Neuromotor ADRs
interactions between psychotropic medications and Extrapyramidal side-effects are the most common
physical health, and discuss pharmacological strategies for neuromotor ADRs of antipsychotics. These side-effects
managing the physical health risks associated with mental can be socially stigmatising and are associated with poor
illness and avoiding psychotropic adverse drug reactions quality of life, treatment dissatisfaction, and non-
(ADRs). adherence to treatment.239,240 Extrapyramidal side-effects
include dystonia (muscle spasm), Parkinsonism
ADRs associated with psychotropic medications (tremor, rigidity, and bradykinesia), akathisia (subjective
Antipsychotic medications are a key component of restlessness), and tardive dyskinesia (abnormal involuntary
treatment for psychotic disorders, because they reduce movements). The detailed mechanisms of these side-
acute symptoms,231 and reduce the risk of relapses,232 effects are unknown, but they are likely to be related to
emergency hospital admissions,233 rehospitalisation,234,235 blockade of dopamine receptors in the nigrostriatal
and mortality.21,236 Antipsychotic medications are also used pathway.250 The annual incidence of tardive dyskinesia is
for bipolar affective disorder.237,238 However, the long-term lower among patients taking SGAs compared with those
effects of ADRs related to physical health are a major taking first-generation antipsychotic medications.251
concern, and can be broadly divided into the following Neuroleptic malignant syndrome is a rare but serious
categories: cardio­ metabolic, endocrine, neuromotor, condition (incidence of one to two cases per 10 000 people
and other ADRs. The ADRs associated with specific per year) that can be life-threatening.252 It is characterised
antipsychotics are described in the appendix (p 17). by fever, severe rigidity, autonomic disturbances, and
confusion.252 The incidence of neuroleptic malignant
Cardiometabolic ADRs syndrome has reduced since SGAs became more widely
Weight gain is an important ADR because it mediates used.252
other cardiometabolic outcomes, such as type 2 diabetes
and cardiovascular diseases. Weight gain is the most Other ADRs
distressing side-effect reported by callers to mental health Antipsychotics are associated with varying degrees of
helplines,188 and is associated with poorer quality of life239–241 cardiac conduction delay, indicated by a prolonged QTc
and barriers to social engagement.242 As a result, patients interval, that can predispose the patient to torsade de
who gain weight have a reduced adherence to treatment, pointes and lead to sudden death.253 Therefore, cardiac
which can lead to relapse and poor mental health conduction should be monitored in patients at risk.
outcomes.163,164 Although most antipsychotic medications Anticholinergic effects are common side-effects of anti­
lead to weight gain, clozapine and olanzapine have the psychotic medications, particularly chlorpromazine,
highest propensity, and haloperidol, lurasidone, and clozapine, and olanzapine.254 Anticholinergic effects
ziprasidone have the lowest propensity.243,244 Weight gain are mediated by antagonism of acetylcholine by inhibition
pathways induced by antipsychotic medication include of the muscarinic receptors. They can be either central
those involving histamine H1 receptors, D2 dopamine (eg, impairment of cognition, memory, and con­
receptors, blockade of 5-hydroxytryptamine receptor 2C, centration, and sedation) or peripheral (eg, constipation,
and dysregulation of glucagon-like peptide-1.243,245 Meta- dry eyes, mouth, and skin, blurred vision, tachycardia,
analyses (table 1) have found that the risk of metabolic and urinary retention). These effects are particularly
syndrome and type 2 diabetes is at least twice as high in burdensome in the older population and can have
people with schizophrenia, bipolar affective disorder, and cumulative effects when multiple anticholinergic agents
major depressive disorder compared with the general are used.254
population (appendix pp 6–13). Somnolence, sedation, and hypersomnia are also
common side-effects of antipsychotics.244 Although
Endocrine ADRs sedation might have short-term benefits for an acutely
Antipsychotic-induced hyperprolactinaemia is the most exacerbated or agitated patient, in the long term,
common endocrine ADR.246 Antipsychotic medications somnolence and sedation can affect physical activity,

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bodyweight, concentration, and the ability to participate side-effects, headache, and sexual side-effects are
in daily activities or psychosocial rehabilitation, and associated with all proserotonergic drugs for depression,
could lead to medication non-adherence.239 whereas sedation, weight gain, and meta­bolic effects vary
Most antipsychotic medications can reduce the seizure across agents. Antihistaminergic agents (eg, mirtazapine)
threshold. The greatest dose-related risk for seizures is are more associated with cardiometabolic effects and
associated with clozapine.253 sedation. Less commonly, drugs for depression can have
cardiac (eg, arrhythmias), neuro­logical (eg, seizures), and
Clozapine hepatic ADRs.275 Treatment with tricyclic antidepressants
Clozapine is the only approved antipsychotic medication is associated with anticholinergic effects, including dry
for people with treatment-resistant schizophrenia.255 It is mouth, sedation, blurred vision, constipation, and urinary
the most effective antipsychotic medication for reducing retention, as well as increased appetite, weight gain,
positive symptoms256 and hospitalisations.257 However, and hyponatraemia (especially in older patients).276
clozapine is associated with severe neutropenia Furthermore, tricyclic antidepressants are associated with
(agranulocytosis; incidence 0·9%; 95% CI 0·7–1·1), a risk of orthostatic hypotension and falls.277 They also
usually in the first month after commencement, that can have a known arrhythmogenic effect; electrocardiogram
rarely cause death (0·013%; 0·010–0·017).258 Cardiac ADRs (ECG) changes can include prolongation of PR interval,
can be life-threatening and include myocarditis (incidence QRS interval, and PT (appendix p 19).
of 0·03–1·00%, usually within the first month)259,260 and
cardiomyopathy (incidence of 0·06–0·12%, usually after Pharmacological management of ADRs and physical
the first year).259,261 Other ADRs of clozapine include weight health comorbidities
gain, type 2 diabetes, sedation, sialorrhoea, constipation, For the physical comorbidities associated with serious
tachycardia, postural hypotension, gastro-oesophageal mental illness that are also commonly seen in the general
reflux, nocturnal enuresis, seizures, and obsessive- population (eg, cardiovascular disease), national and
compulsive symptoms.262 international prescribing guidelines developed for the
general population should be followed. By contrast,
Mood stabilisers conditions that are secondary to psychiatric pharmaco­
Mood stabilisers are prescribed for bipolar affective logical treatment (eg, extra­pyramidal side-effects) require a
disorder263 and adjunctively for refractory schizophrenia.264,265 specialised approach. Close monitoring of physical health
Individuals who are prescribed lithium have a mean parameters is required for people taking antipsychotic
weight gain of 4 kg over 2 years.266 Lithium is also associated medications, and evidence-based pharma­ cological treat­
with thyroid disease,267 including development of goitre ments are needed.278 If it is safe and feasible, modifying
(in up to 50% of patients268), hypo­thyroidism,269 or hyper­ psychiatric medications that are associated with an ADR
thyroidism.270 Lithium is also associated with polydipsia, (eg, by reducing doses or switching medications) should
polyuria, diabetes insipidus, and other forms of renal be considered, in consultation with the patient. Here, we
dysfunction.269 Sodium valproate is associated with provide a targeted, evidence-based approach to addressing
metabolic effects, with at least half of individuals gaining com­monly observed physical health ADRs in patients with
weight in the first 3 months after initiation,271 with a mean severe mental illness.
weight gain of 6·4 kg over 3 months.272 It is also associated
with insulin resistance, which increases the risk of Type 2 diabetes
developing type 2 diabetes.273 Pharmacological management of type 2 diabetes for
Antipsychotic medications are often prescribed con­ patients with severe mental illness should follow guidelines
currently with mood stabilisers; additional caution is for the general population (appendix p 20). The first-line
required in this situation because the metabolic effects of pharmacological therapy is metformin monotherapy, and
the two classes of medication could be additive.93 Although second-line therapies are listed in the appendix (p 20). The
lithium and sodium valproate are the two most widely relative risks and benefits of different type 2 diabetes
prescribed mood stabilisers, other mood stabilisers have a treatments for patients with severe mental illness are
lower propensity for weight gain (eg, carbamazepine)271 presented in table 3. Metformin reduces the risk of
or have no effect on weight (eg, lamotrigine).274 All transition from prediabetes to type 2 diabetes,283,284 and
mood stabilisers are associated with teratogenic effects should be considered for individuals with severe mental
and should be avoided in pregnancy and lactation illness and prediabetes. Glucagon-like peptide 1 receptor
(appendix p 18). agonists also reduce the transition from prediabetes or
non-diabetes to type 2 diabetes, as well as leading to
Drugs for depression clinically significant weight loss.282
Common ADRs with newer-generation drugs for
depression include headache, nausea, agitation, sedation, Weight gain
dizziness, sexual dysfunction, hyponatraemia, weight When behavioural interventions are ineffective, pharmaco­
gain, and metabolic abnormalities.275 Gastro­intestinal logical methods for attenuating weight gain in patients

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Mechanism Risks Benefits Evidence base in severe mental

illness
Biguanide (metformin) Increases insulin sensitivity; reduces Lactic acidosis; B12 deficiency; Weight loss (3 kg); low risk of Good evidence for use in patients
hepatic synthesis and release of gastrointestinal effects (a modified hypoglycaemia with severe mental illness, and
glucose; increases peripheral glucose release formulation can be tried if these should be considered a first-line
uptake occur); contraindicated in patients with treatment;279 consider use in patients
estimated glomerular filtration rate with pre-diabetes who are receiving
<30 mL/min per 1·73 m² olanzapine and clozapine280
DPP4 inhibitor Inhibits action of DPP4 that acts to Possible increase in hospitalisations for No effect on weight; low risk of Insufficient trial data in patients with
(eg, sitagliptin) break down incretins (eg, GLP-1), heart failure with alogliptin and hypoglycaemia severe mental illness
resulting in increased incretin effect, saxagliptin; possible increased risk of
as seen with GLP-1 receptor agonists pancreatitis
GLP-1 receptor agonist Incretin mimetic: stimulates release Nausea or vomiting; possible increased Weight loss (3·0–4·5 kg); low risk of Current evidence base suggests it
(eg, exenatide) of insulin; reduces glucagon release; risk of pancreatitis; subcutaneous hypoglycaemia; liraglutide is approved should be considered a second-line
delays gastric emptying; reduces administration by the FDA for prevention of major therapy in patients with severe
appetite cardiac events mental illness; some evidence for the
use of exenatide in patients treated
with clozapine;281 GLP-1 receptor
agonists have been shown to reduce
the transition to type 2 diabetes282
Sulfonylurea Increases endogenous production of Weight gain; hypoglycaemia None established Insufficient trial data in patients with
(eg, gliclazide) insulin severe mental illness
SGLT2 inhibitor Inhibits SGLT2 in the proximal renal Polyuria; postural hypotension; urinary Weight loss (2–3 kg); low risk of Insufficient trial data in patients with
(eg, dapagliflozin) tubule, thereby reducing reabsorption tract infection; diabetic ketoacidosis can hypoglycaemia; empagliflozin is severe mental illness
of glucose and promoting glucosuria occur in stress settings; mild fracture risk approved by the FDA to reduce
cardiovascular mortality; canagliflozin
reduces cardiac events
Thiazolidinedione Improves insulin sensitivity by Weight gain; heart failure; oedema; bone Might reduce stroke risk; low risk of Insufficient trial data in patients with
(eg, pioglitazone) promoting adipogenesis and fractures hypoglycaemia severe mental illness
reducing circulating fatty acid and
lipid availability
Insulin Supplements the insufficient Weight gain; hypoglycaemia In acute settings or in poorly controlled Insufficient trial data in patients with
endogenous production of insulin type 2 diabetes, it might be the only severe mental illness
effective treatment for stabilising sugars
DPP4=dipeptidyl peptidase 4. GLP-1=glucagon-like peptide 1. FDA=US Food and Drug Administration. SGLT2=sodium-glucose cotransporter 2.

Table 3: Risks and benefits of different drug classes for diabetes treatment and the evidence base for their use in patients with severe mental illness

with severe mental illness should be considered. psychosis (eg, QRISK3 calculator),290 inform decisions
Pharmacological agents are described in detail in the about the initiation of statin therapy.291 The pharmacological
appendix (p 21); the most evidence in individuals treated management of dyslipidaemia in patients with severe
with drugs for psychosis is for metformin and topiramate.285 mental illness should follow guidelines used in the
Bariatric surgery can also be considered as a last-resort general population (panel 3). No strong evidence is
treatment if both behavioural and pharma­ cological available to support targeting hypertriglyceridaemia
interventions are not effective. Weight gain associated with therapeutically to decrease cardiovascular risk.
drugs for psychosis is not usually dose-dependent, so dose
reduction will not be effective in reducing weight.286 Sinus tachycardia
Sinus tachycardia in patients with severe mental illness
Arterial hypertension could be a feature of the illness, of drug withdrawal, or of
Pharmacological management of hypertension in patients an acute drug reaction (eg, serotonin syndrome or
with severe mental illness should follow guidelines used neuroleptic malignant syndrome). Psychotropic-related
for the general population (appendix p 20). tachycardia is persistent, and usually dose-related.295 If
dose reduction or switching medication is not feasible,
Dyslipidaemia and inappropriate sinus tachycardia has been confirmed
Data on dyslipidaemia treatments that are specific for (including a 24-h ECG), the first-line treatment is a
people with mental illness are scarce. Therefore, the best cardioselective β blocker (eg, atenolol 25–100 mg per day)
guidance available comes from general population with uptitration until the heart rate normalises
studies. Statins reduce the risk of coronary heart disease (60–100 beats per min). If β blockers are not tolerated
events by 20–30%.287–289 Cardio­vascular risk calculators that (eg, in patients with postural hypotension), or are
incorporate factors such as age, hypertension, and type 2 ineffective, then ivabradine (5·0–7·5 mg twice a day) can
diabetes diagnosis, and particularly those that include be introduced.296 Ivabradine has been shown to be
diagnosis of severe mental illness and use of drugs for effective and tolerated in clozapine-induced tachycardia.297

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first-generation antipsychotics.301 If dose reduction of the

Panel 3: General principles for prescribing causative medication is unsuccessful, a switch to
antihypertensives and statins to people with severe quetiapine, olanzapine, or clozapine can be con­
mental illness sidered.302,303 Other treatments include β blockers (eg,
Antihypertensives propranolol 30–90 mg per day),304 5-hydroxytryptamine
• If the patient has no indications for a specific medication, receptor 2 antagonists (eg, mirtazapine 15 mg per day,
then any of the following four medication classes can be mianserin 30 mg per day, or cyproheptadine 16 mg per
used as first-line treatment:292 thiazide diuretics, day),304–306 antimuscarinics (eg, benzatropine 6 mg per
long-acting calcium-channel blockers (eg, amlodipine), day),307 and benzodiazepines (eg, clonazepam 0·5–3·0 mg
angiotensin-converting enzyme inhibitors, and per day).304 Tardive dyskinesia occurs in 5% of patients per
angiotensin II receptor antagonists year of exposure to drugs for psychosis.251 If tardive
• A thiazide-like diuretic or long-acting dihydropyridine dyskinesia occurs, it is recommended that anticholinergics
calcium-channel blocker should be used as the initial are stopped and treatment is rationalised (ie, stopping the
monotherapy for black patients293 causative drug or reducing the dose), with clozapine most
likely to provide symptomatic relief.308 Adjunctive treat­
Statins ments include tetrabenazine,309 and novel vesicle mono­
• Consider using a cardiovascular disease risk assessment amine transporter type 2 inhibitors that have been
tool (eg, QRISK3 calculator)290 to guide whether statins approved by the US Food and Drug Administration, such
should be used; measure total and HDL cholesterol to as valbenazine and deutetrabenazine.310
achieve the best estimate of cardiovascular disease risk294
• Before offering statins to the patient for primary prevention Anticholinergic effects
of cardiovascular disease, discuss the benefits of lifestyle The first-line management of anticholinergic ADRs of
modification, and optimise the management of other drugs for psychosis is dose reduction, if it is feasible.298
modifiable cardiovascular disease risk factors, if possible For constipation caused by an anticholinergic-related
• Offer statin therapy (eg, atorvastatin 20 mg once a day) reduction in gastric motility,311 stool softeners (eg,
for primary prevention of cardiovascular disease if the macrogols or docusates) and a stimulant laxative
QRISK3 assessment tool shows that the individual has a (eg, senna) might be effective.312 For patients taking
10-year risk of developing cardiovascular disease of 10% clozapine, sialorrhoea is common. Augmentation with
or higher294 diphenhydramine or benza­ mide antipsychotics (eg,
amisulpride) can ameliorate sialorrhoea.313

Postural hypotension Sexual side-effects

In addition to the causes of postural hypotension that Sexual side-effects can include reduced libido, delayed
exist in the general population, it can be related to or blocked ejaculation, erectile dysfunction, decreased
taking psychotropic medication, notably clozapine and orgasm, persistent genital arousal, lactation, and numb­
quetiapine.298 If increased fluid intake and salt ness of the vagina or nipples. Patients with sexual
consumption are ineffective, a dose adjustment or switch side-effects should be assessed by examining
of the responsible psychiatric medication should be prolactin concentration, concomitant medications, and
considered if safe to do so. If dose adjustment or comorbid causes (which can be psychological or
medication switch is not feasible, non-pharmacological physical—eg, diabetes or cardiometabolic disease).298 If
therapy (appendix p 22) with regular blood pressure prolactin is elevated, the antipsychotic dose might need to
monitoring should be undertaken. be reduced or the drug might need to be switched.
Alternatively, low-dose aripiprazole could be prescribed.298
Extrapyramidal side-effects Patients who are taking SSRIs and have sexual
Around 10% of individuals who are taking antipsychotic dysfunction could be switched to another drug for
medications have acute dystonia.299 It is more common in depression, or given a trial of bupropion or sildenafil, if
antipsychotic-naive individuals, and can occur rapidly appropriate.314
after the initiation of the drug for psychosis. Acute dystonia
can be treated with an anticholinergic medication Thyroid disease
(eg, benzatropine), which is given orally, intramuscularly, In patients with hyperthyroidism who are taking lithium,
or intravenously, depending on urgency. Parkinsonism is a pertechnetate scan might be required to determine the
seen in approximately 20% of individuals taking anti­ cause of the thyroid disorder. Graves’ hyperthyroidism or
psychotic medications.300 If changing medication or toxic multinodular goitre can be treated with thionamides,
reducing the dose is not effective or feasible, patients can radioiodine, or surgery, whereas if the patient has lithium-
be given an anticholinergic medication. The risk of induced thyroiditis, cessation of lithium should be
akathisia varies for different drugs for psychosis, but considered.267 Lithium-induced hypothyroidism can occur
is estimated to occur in 25% of individuals taking in the presence or absence of goitre. When lithium-induced

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hypothyroidism is present, treatment with levothyroxine with mental illness.323 Nicotine replacement therapies
is indicated, according to general guide­ lines for the should be used for approximately 8–12 weeks. Different
management of primary hypothyroidism.315 Lithium- preparations are available, including sublingual tablets,
induced goitre requires an ultrasound examin­ ation to gum, patches, nasal spray, inhalators, lozenges, and
assess for diffuse versus nodular enlargement, and where electronic cigarettes (e-cigarettes). Bupropion and
appropriate, fine needle aspiration should be done to vareni­cline can increase the likelihood of successful
guide diagnosis. Levothyroxine might stabilise or reduce smoking cessation without increasing the risk of
lithium-induced goitre.316 Because of the high incidence of neuropsychiatric events in people with severe mental
thyroid disease in patients who are taking lithium, illness.324
baseline clinical thyroid examination and sero­ logical In conclusion, the burden of ADRs associated with
assessment of thyroid function is recommended, with at psychotropic medications is important to consider in
least annual monitoring during treatment. The develop­ the context of treatment effectiveness and patient
ment of thyroid dysfunction while taking lithium does not acceptability. Drugs for psychosis (or antipsychotics) are
usually require lithium therapy to be stopped; the risks the best evidence-based treatments for psychotic disorders,
and benefits of continuing treatment should always be and lead to lower all-cause mortality in schizophrenia than
considered. giving no treatment.325 Mood stabilisers are the most
effective treatment for bipolar affective disorder,263 and
Renal disease drugs for depression (or antidepressants) have an impor­
Lithium-induced nephrogenic diabetes insipidus, with tant role in the treatment of depression.326 Careful and
associated polyuria and polydipsia, can affect a patient’s regular monitoring of laboratory and clinical parameters
quality of life. It is usually at least partially reversible with could help to identify ADRs early, and prevent the
cessation of lithium, although it can be permanent after development of iatrogenic comorbidities. We would advise
prolonged therapy.317 If ongoing lithium treatment is against ceasing or switching psychotropic treatments to
required and the patient only has a mild-to-moderate modalities that are less effective without careful con­
renal-concentrating defect, the introduction of amiloride sideration of the risk of relapse. Involvement of the patient
(which is thought to reduce the accumulation of lithium in treatment decisions is important when balancing the
in collecting tubule cells) can reduce urine volume, effectiveness of a medication against its ADRs.327
increase urine osmolality, and improve responsiveness to
antidiuretic hormone.318 Thiazide diuretics with a low- Part 4: Multidisciplinary approaches to
sodium diet have also been found to have a paradoxical multimorbidity
effect of reducing urinary output in nephrogenic diabetes Lifestyle interventions: what works?
insipidus.319 For patients with chronic kidney disease Modifiable lifestyle factors, such as physical activity, diet,
secondary to chronic interstitial nephritis, lithium and smoking, are increasingly recognised as being
cessation might be indicated if renal insufficiency fundamental to both physical and mental health.
progresses. Some renal function might be recovered Interventions targeting these modifiable risk factors,
after discontinuation of lithium, although progressive delivered by practitioners with specific expertise, are
renal failure can occur.320 Regular monitoring of renal referred to as multidisciplinary lifestyle interventions.
function is required, and monitoring of other risk factors The efficacy of such multidisciplinary lifestyle inter­
for renal failure (eg, hypertension and diabetes) is also ventions in reducing the risk of cardiometabolic-related
important. morbidity in the general population is well established.283
Accordingly, the 2018 WHO guidelines328 recommend
Nicotine and smoking cessation that lifestyle interventions are considered as first-line
Smoking, and its associated physical morbidity, is a key strategies for the management of physical health
contributor to the excess mortality of individuals with (including weight management, cardiovascular disease
mental illness.321,322 Therefore, reducing smoking rates is a and cardiovascular risk reduction, and diabetes
priority. However, clinicians should be aware that abrupt treatment and prevention) in adults with severe mental
smoking cessation can change the pharmacokinetics and illness. However, a broad spectrum of mental disorders,
pharmacodynamics of many psychotropic medications not only severe mental illness, are associated with high
(eg, increasing blood concentrations of clozapine, and to rates of cardiometabolic diseases (Part 1) and lifestyle
a lesser extent olanzapine and fluvoxamine). Patients who risk factors (Part 2) that are compounded by the
are planning to stop smoking should be followed up medications that are commonly used to treat mental
closely; plasma concentrations of medications should be illnesses (Part 3). Thus, a first step in reducing physical
monitored, if possible, and appropriate dose adjustments health disparities for people with mental illness is
should be made. the adoption, translation, and routine provision of
In the general population, nicotine replacement therapy evidence-based lifestyle interventions as a standard
increases the odds of successful smoking cessation by component of mental health care. However, not all
1·5–2·0 times, with good evidence of efficacy in patients lifestyle interventions are equally useful. The efficacy

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Panel 4: Key components of lifestyle interventions

Smoking cessation • Policy-level interventions can also be implemented; for
Challenge: general population approaches have not worked for instance, in 2016 NHS England announced that all mental
people with mental illness health services would become smoke free, which included a
• Although smoking rates have substantially decreased ban on smoking on mental health wards and hospital
for the general population since the mid-1990s, they have premises, and the dissemination of smoking cessation
remained high for people with mental illness;329 as a result, interventions throughout community care.335 Initial data
people with mental illness now consume around half of all suggest that smoking bans and bespoke smoking cessation
cigarettes sold in the USA, Australia, and the UK321,330 programmes are well received in inpatient settings, and
• People with mental illness are as motivated to stop they could have broader benefits by supporting a culture of
smoking as people without mental illness, but they are physical health and wellbeing within mental health
more nicotine-dependent and less likely to seek out and services336
receive appropriate interventions tailored to their Future research priorities: improve the accessibility and timing of
needs331,332 cessation interventions
• Smoking-related deaths disproportionally affect people • Training on smoking cessation is now freely available online
with mental illness, and smoking is a leading cause of for health-care professionals, which could increase access to
the premature mortality observed in this population321,322 evidence-based interventions for people with mental illness;
Emerging solution: specialised cessation interventions for instance, a concise e-learning tool on smoking from the
• Evidence on pharmacological interventions shows that they National Centre for Smoking Cessation and Training330 could
could be effective; for instance, a 2016 meta-analysis324 help front-line mental health staff to deliver smoking
showed that bupropion and varenicline were the most cessation advice
effective interventions for smoking cessation for people • Electronic cigarettes (e-cigarettes) are already widely used
with severe mental illness, and both resulted in a five times among people with a range of mental health disorders,337 and
increase in smoking cessation compared with placebo are a potentially useful tool for reducing smoking-related
treatments deaths. The UK Science and Technology Committee has
• For non-pharmacological interventions to be effective, advised mental health trusts to allow e-cigarette use on their
they must account for the additional barriers to treatment premises; however, e-cigarettes are not authorised or
that people with mental illness can have (eg, cognitive available in many countries, and further research is required
impairments);333 for instance, the SCIMITAR+ programme is to establish the health outcomes of using e-cigarettes as a
a candidate model of a bespoke smoking cessation smoking harm-reduction intervention338
intervention for people with severe mental illness, which • Early intervention for smoking is feasible,339 and could improve
was developed with service users to address the needs of cessation rates and long-term physical-health outcomes340
this population334
(Continues on next page)

and effectiveness of multidisciplinary lifestyle inter­ tailoring of materials and strategies to address ethnic
ventions are impacted by both their content and timing diversity; and an extensive network of training, feedback,
of delivery. Some key considerations for the individual and clinical support.283
components of multidisciplinary interventions are The primary study on DPP284 recruited 3234 adults
presented in panel 4. without diabetes who were at risk of developing type 2
Although it might seem counterintuitive to dedicate diabetes (established via multiple risk factors); patients
intensive resources to individuals with relatively good were assigned to receive placebo, metformin, or a lifestyle
metabolic health, focusing on cardiometabolic protection intervention that involved at least 150 min of physical
in at-risk populations could be the optimal approach for activity per week with the goal of at least a 7% weight
lifestyle interventions (panel 2). The Diabetes Prevention loss. The lifestyle intervention resulted in a 58% reduction
Program (DPP),283 developed and evaluated in the USA, in the development of type 2 diabetes over the 3-year
is an example of a gold-standard lifestyle intervention study, with 4·8 cases of diabetes per 100 person-years
(panel 5). The key features of DPP include individual observed in the lifestyle intervention group, compared
case managers; frequent face-to-face contact with with 11·0 cases in the placebo group (incidence in the
participants; a structured educational component that metformin group was 7·8 cases per 100 person-years).283,284
includes behavioural self-management strategies; Furthermore, both the clinical benefits and cost-
supervised physical activity sessions; a maintenance effectiveness of the DPP lifestyle intervention were
intervention that combines group and individual maintained over a 10-year follow-up, as compared with
approaches, motivational strategies, and individualisation metformin as the control condition.361,362 These results
through a so-called toolbox of adherence strategies; show that lifestyle interventions with beneficial

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(Panel 4 continued from previous page)

Physical activity Diet

Challenge: patients find it difficult to stay motivated Challenge: additive effect of medication and diet
• Weight loss is often a primary motivation factor for physical • Dietary risks are a leading risk factor for cardiometabolic
activity,341 but exercise alone in the absence of dietary disease identified by the Global Burden of Disease Study;353
modification will not reliably reduce a patient’s bodyweight, for people with mental illness, the risk is exacerbated128,138
particularly in the short term;342 exercise can attenuate because of the side-effects of psychotropic medications (eg,
further weight gain, but weight maintenance might not be a excessive or insatiable hunger, cravings for high-calorie,
strong motivator for people with mental illness, particularly low-nutrient foods),183,354 an insensitive reward system and
if they were overweight before the onset of mental illness, poor cognitive control,355 and food insecurity and financial
which can result in disengagement with exercise constraints356
Emerging solution: fitness goals designed by fitness professionals Emerging solution: dietary support
• Rather than focusing on weight loss, improving fitness might • Improved diet quality357 and reduced bodyweight358 are both
be a more motivating341 and achieveable343,344 goal for exercise associated with decreased mortality in the general
interventions for people with mental illness; improving fitness population
can also have important health benefits, because even a • Dietary interventions in people with mental illness are more
modest improvement is associated with a 15% decrease in effective if they are delivered by specialist clinicians, such as
mortality in the general population345 dietitians, and at an early stage of treatment;359
• Exercise interventions delivered by qualified exercise cardiometabolic care and subsequent dietary intervention
professionals (with a university qualification in exercise should be implemented within a multidisciplinary
prescription, such as physiotherapists or exercise framework360
physiologists) have significantly greater physical and Future research priorities: personalised pathways to health and
psychological benefits and adherence compared with fitness
interventions delivered by non-specialised practitioners.346–348 • As with exercise, the most effective dietary regime for
In addition, the integration of qualified exercise professionals people with mental illness will be one that is sustainable;
into mental health services could ensure that mental health future research might identify strategies that alleviate the
staff have the knowledge and training to give clear advice on obesogenic effects of psychotropic medications, and that
exercise address the insensitive reward system and poor cognitive
Future research priorities: varied and personalised exercise control of some people with mental illness
programmes • Links between dietary intake, the microbiome,
• Although most research on physical activity has focused on inflammation, and obesity are increasingly becoming clear,
aerobic exercise, evidence from the general population and could provide new ways to improve physical outcomes
increasingly shows that strength and resistance training or for people with mental illness
so-called high-intensity interval training can have beneficial
effects for both metabolic and mental health349–351
• Given that enjoyment and satisfaction are key factors in
determining exercise adherence,352 offering a range of
exercise options that accommodate patient preferences and
goals will be important for establishing sustainable and
engaging exercise routines

components (panel 5) can reduce the incidence and treated in primary care settings. Furthermore, evidence
burden of cardiometabolic diseases when used as a increasingly shows that supervised exercise training (a
preventive strategy in at-risk populations. Notably, the key component of the DPP) can improve psychiatric
DPP has also been adapted and successfully delivered in symptoms, cognition, and functioning across a range of
primary-care settings.363 mental health diagnoses.346,364,365 Therefore, integrating
Considering the increased metabolic and lifestyle risk the DPP principles into mental health care could improve
observed across multiple classes of mental health overall recovery, not only metabolic health. However, the
disorder (Parts 1 and 2), the DPP could be adapted for majority of DPP studies to date have excluded individuals
people with mental illness and made available through with a “major psychiatric disorder which, in opinion of
primary care, on a referral basis. The use of such clinic staff, would impede conduct of the DPP”.284 The
transdiagnostic, evidence-based, and cost-effective DPP needs to be analysed as a transdiagnostic lifestyle
lifestyle interventions could help to protect the cardio­ intervention for people with mental illness through
metabolic health of people with mental illness who are primary care services and specialised mental health

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Conversely, in some situations, adaptation of evidence-

Panel 5: Lifestyle intervention guidelines adapted from the Diabetes Prevention based programmes for people with mental illness can
Program283 threaten their effectiveness. For instance, reducing the
Measurable and specific goals amount or frequency of interventional components,
• Maintain bodyweight or reduce by between 5% and 7% of total bodyweight because of conflicting demands on the priorities and
• Reduce calorie intake (500–1000 kcal less than the calorie intake needed for weight workload of mental health staff and diagnostic
maintenance per day, and a maximum of 25% of calories from fat), and improve diet overshadowing,20 could mean the programme is
quality insufficient to effect change for those patients. The
• Increase the number of minutes of physical activity (meet recommendations of challenge for policy makers, clinicians, and service
150 min per week of moderate-to-vigorous physical activity) providers is to apply established, effective principles of
• Replace sedentary behaviour with light intensity activity as often as possible behaviour change to people with mental illness,
• Increase cardiorespiratory fitness particularly with regards to adopting a framework of
• Cessation of smoking early intervention and prevention.13

Case managers or lifestyle coaches with university (or equivalent) training in Implementing lifestyle interventions for severe mental
nutrition and dietetics, exercise prescription, or behavioural change illness
• Allow for individualised programme design and delivery A 2019 meta-review285 aggregated data from 27 meta-
• Offer a combination of group sessions and one-on-one sessions analyses of physical health interventions for people with
• Provide supervised exercise and nutrition sessions at least two times per week schizophrenia. Exercise, diet, and broader lifestyle
(eg, community centre sessions, neighbourhood group walks, or one-on-one personal interventions (eg, sleep hygiene, smoking cessation
training) strategies, motivational interviewing) had significant
• Do relevant assessments at regular intervals benefits for multiple cardiometabolic outcomes
• Ensure lifestyle coaches have training in psychopathology and the basic principles of (including bodyweight, waist circumference, blood
working with people with mental illness pressure, and glucose and lipid markers), with a similar
Frequent contact and ongoing intervention efficacy to pharmacological management of metabolic
• Deliver core curriculum on topics including nutrition (modifying energy intake), health.285 However, the clinical trials from which these
physical activity (and sedentary behaviour), and behavioural self-management efficacy data were predominantly derived could reduce
(barrier identification and problem solving) the generalisa­bility and external validity of the findings,
• Provide a flexible maintenance programme with supplemental group classes because trials are rarely done under real-world conditions
• Provide motivation campaigns and restart opportunities and are typically resourced differently to routine clinical
care.367
Individualisation through a toolbox of adherence strategies Few studies have been done on the effectiveness,
• Self-monitoring of outcomes and behaviours, such as weight, physical activity, pragmatic implementation, or sustainability of life­
sedentary behaviour, and dietary intake (fat and calorie intake) style interventions in people with mental illness.368
• Barriers to treatment are identified and addressed with simple, individualised Furthermore, several large-scale clinical trials in people
resources (eg, a cookbook might be given to a patient trying to improve their diet) with mental illness have had null findings. To provide
Strategies that are adapted for culturally and ethnically diverse groups guidance on effective implementation of lifestyle inter­
• Translation of documentation to local languages ventions within mental health services, the inter­ventions
• Identification of culturally appropriate resources and intervention approaches that are associated with negative and positive outcomes in
• Cooking groups that allow for dietary restrictions or religious requirements trials should be considered. Trials of lifestyle interventions
in mental health care often do not meet all the principles
Local and national network of training, feedback, and clinical support of programmes such as the DPP (appendix p 23). Specific
• Appropriate training of existing and emerging mental health staff aspects of the DPP that have been poorly implemented in
• Clear referral pathways and the integration of lifestyle coaches into a standard trials are: (1) using qualified exercise professionals and
multidisciplinary mental health team dietitians to deliver lifestyle interventions, (2) providing
• Monitoring and evaluation of effectiveness and adherence sufficient access to supervised exercise services, and
(3) ensuring that existing mental health staff are familiar
with the lifestyle interventions. Large-scale clinical trials
services. Although the core principles of the DPP are of lifestyle interventions addressing multiple risk factors
crucial to its design and delivery, more support is likely to in people with mental illness are described in the
be required by people with severe mental illness appendix (pp 24–30).
compared with the amount needed to effect change in The high acceptability of lifestyle interventions among
the general population. A randomised controlled trial of patients365,366,369,370 means that they are a novel route to reach
an adapted version of the DPP for people with severe typically disengaged service users in more traditional
mental illness found significant reductions in obesity mental health treatment. For example, providing gym-
and other metabolic risk markers associated with based resistance exercise is a potential clinical pathway to
antipsychotic treatment compared with usual care.366 care for young people with early psychosis,369 or veterans

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with post-traumatic stress disorder.371 However, an who have been discharged might find it difficult to
important consideration is how such programmes are stay engaged with lifestyle changes. One strategy
applied across different clinical and broader public health for sustaining engagement with health behaviour
settings. Flexibility in delivery, a focus on practical exercise interventions is the use of primary care referral
and dietary advice, and provision of support to integrate schemes. For example, exercise referral schemes for
the lifestyle measures into daily life are highly recom­ people with mental illness typically involve health-care
mended.372,373 Further research is needed on how inter­ providers referring individuals to community-based
ventions are delivered; a mixed model that involves both organisations to provide free (or discounted) access to
online and face-to-face delivery is a potentially balanced a wide range of fitness activities, facilities, and
and cost-effective way forward (appendix pp 31–34).206,193 expertise through community leisure centres and
services. Community-based interventions might also
Training health professionals for a culture shift be a non-resource-intensive strategy for maintaining
Multidisciplinary teams in mental health settings are physical activity behaviour in a way that complements
rapidly evolving to include allied health professionals and supports clinician-led strategies. Exercise referral
with expertise in nutrition, physical activity, behaviour has already been introduced through multiple large-
change, and other aspects of mental health, such as scale implementation projects for sedentary adults in
psychoeducation and mindfulness training. For this primary care in the UK, although only small beneficial
transition to be successful, allied health practitioners effects have been found to date.172,377 However,
should receive at least introductory training in preliminary data show that community exercise can be
psychopathology and in the principles of working with beneficial and engaging for young people with mental
patients with mental illness. Accordingly, the curriculum illness, including for those with severe conditions.378,379
for health professionals, including dietitians, physio­ Community-based diet programmes, such as Weight
therapists, and exercise physiologists should be updated Watchers, are cost-effective weight-loss interventions
to reflect the increasing role for such professionals within when delivered via primary care to obese individuals.370,380
mental health teams.374 Research is now warranted to determine the suitability
In addition, medical and mental health professionals and effectiveness of such programmes for psychiatric
should receive training on working with allied health populations.
professionals in an integrated manner, and understanding Mobile device health (or mHealth) technologies could
the principles of lifestyle interventions. The importance of provide new routes for applying adapted versions of
training medical students in so-called lifestyle medicine is programmes such as the DPP in patients with mental
increasingly being recognised globally.375 Efforts towards illness. For example, a pilot study381 found that FitBit
integrating lifestyle interventions within routine mental activity trackers could potentially be used alongside
health care should avoid an isolated focus on individual- fitness applications (apps) in people with schizophrenia
level behavioural changes, and should also include to deliver DPP-based interventions, with features such as
broader changes to service structure, delivery, and culture daily prompts, motivational messages, and self-
(see Part 5). For instance, evidence suggests that medical determined step-count goals. Participants found the
and nursing practitioners who have healthy lifestyle technology to be engaging, motivating, and empowering,381
behaviours are more likely to recommend such behaviours but a small sample size (n=25) makes it difficult to
to patients.376 Advances in implemen­tation science could determine efficacy. Although they have only been
also provide ways to ensure that lifestyle interventions evaluated in small-scale pilot studies to date, mHealth
have meaningful benefits for patient outcomes.368 technologies present potential opportunities to deliver a
wide range of novel, scalable, and sustainable lifestyle
Barriers, opportunities, and future research interventions for people with mental illness. mHealth
Some of the issues, emerging solutions, and research interventions could also be disseminated easily, even in
priorities for smoking cessation, physical activity, and low-resource settings. Therefore, further development
dietary interventions for people with mental illness are and evaluation of evidence-based mHealth interventions
presented in panel 4. For all types of lifestyle intervention, for improving physical health in people with mental
a gradient of intervention intensity, or so-called stepped illness is warranted.
care, needs to be considered. For example, intervention In conclusion, the principles of existing gold-standard
intensity might vary between individuals, treatment prevention programmes, such as the DPP, can be used
settings, and cultures, and could depend on the readiness as a benchmark for the implementation and maintenance
to provide lifestyle interventions, particularly in low- of lifestyle interventions as an integrated, routine
resource settings. component of mental health care (panel 5). However,
Even in high-resource settings, only providing programmes might need to be adapted to specific care
intensive lifestyle interventions through mental health settings, and for particular patient needs. Efforts are
services could cause issues for individuals who do required to translate the DPP principles into both
not attend mental health centres frequently; those (1) preventive, transdiagnostic lifestyle interventions

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available through primary care, and (2) intensive Part 5: Innovations in integrating physical and
interventions for specialist services. If these efforts are mental health care
successful, effective programmes for protecting the Introduction
cardiometabolic health of people living with mental Social determinants, including poverty, poor education,
illness could be implemented. unemployment, homelessness, and childhood abuse,

Directions and rationale Actioned by

Treating syndemics Examining how broader societal factors affect the interaction between Led by public health; developed and
physical and mental health conditions within a given region can implemented by national and local health-care
provide insight into these comorbidities and their risk factors; in turn, providers
this can inform the development and implementation of preventive
strategies and interventions for chronic health conditions within a
given socioeconomic setting
Preventing multimorbidity Evidence-based integrated care should be provided from the onset of Led by public health; delivered by primary,
mental illness; changes are needed at the primary, secondary, and secondary, and tertiary care, and community
tertiary levels of care to reduce the prevalence and impact of physical groups
health conditions in people with mental illness (panel 5)
Primary and parallel care Primary care is the first point of contact for most patients, and is an Led by commissioners of health-care
important part of care after discharge from specialist services. organisations; developed via culturally sensitive
Implementing integrated models of mental and physical health care integrated care models designed by local health
through primary care services could be effective for efficient professionals; and implemented by health-care
management of physical health comorbidities in people with mental practitioners
illness; however, the management of comorbid substance use disorders
might depend on improving accessibility, referral pathways, and quality
of dedicated parallel services
Implementation in low-income Incorporating integrated care models within the emerging Led by commissioners of health-care
and middle-income countries mental health services of low-income and middle-income countries is organisations; developed via culturally sensitive
important for reducing physical health inequalities for people with integrated care models designed by local health
mental illness, and might also provide a more cost-effective approach professionals; and implemented by health-care
to health-care provision in these settings practitioners
mHealth technology solutions mHealth technology and other digital technologies provide many novel Led by mental health commissioners; developed
methods for promoting physical health and delivering interventions with communities, researchers, and industry;
remotely. The low cost, scalability, and global accessibility of such and implemented by health-care practitioners
approaches are highly appealing, particularly in low-income and
middle-income settings; while the evidence-base is still nascent, this
can be considered a high-priority area for future research
mHealth=mobile device health.

Table 4: Considerations and directions for integrating health care

Year Organisation Illness Outcomes

Management of physical health conditions in adults with 2018 WHO Severe mental illness Morbidity, premature
severe mental disorders: WHO guidelines328 mortality
Health matters: reducing health inequalities in mental 2018 Public Health Severe mental illness Morbidity, premature
illness330 England mortality
Bringing together physical and mental health: a new 2016 King’s Fund, All mental illness Cardiometabolic health
frontier for integrated care386 London, UK
Improving physical healthcare for people living with 2018 NHS England Severe mental illness Premature mortality
severe mental illness in primary care: guidance for CCGs387
The physical health of people with mental health 2017 Te Pou, Auckland, Severe mental illness Mortality, morbidity
conditions and/or addiction388 New Zealand
Excess mortality in persons with severe mental disorders: 2017 World Psychiatric Severe mental illness Premature mortality
a multilevel intervention framework and priorities for Association
clinical practice, policy, and research agendas121
Helping people with severe mental disorders live longer 2017 WHO Severe mental illness Premature mortality
and healthier lives149
Improving the physical health of adults with severe 2016 Royal College of Severe mental illness Premature mortality
mental illness: essential actions389 Psychiatrists

CCG=clinical commissioning group.

Table 5: Key resources on the integration of physical and mental health

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increase the risk for both mental and physical

illnesses.182,382 The relationships between adversity, Panel 6: Prevention of physical health morbidity and
physical health, and mental health are complex, and risk mortality in individuals with mental illness
factors can act synergistically to reinforce disadvantage Primary prevention
and disability.182 For instance, people with mental illness Primary preventive strategies aim to provide people with the
are more likely to be in poverty and to have cardiometabolic tools needed to live a healthy lifestyle190 by avoiding smoking,
and infectious diseases (see Parts 1 and 2), and conversely, alcohol and substance misuse, poor diet, and physical
chronic physical health conditions and social deprivation inactivity. Among those with mental illness, a healthy
are key risk factors for mental illness.182,383,384 A 2017 Lancet lifestyle should ideally be adopted in the early stages of illness
Series385 on the co-occurrence of chronic health conditions to build healthy habits, and to protect physical health as
described how syndemic frameworks could be used to much as possible. Primary prevention strategies need to be
understand how health risks and comorbidities interact adapted for people with mental illness, because public health
with one another within the broader environmental strategies that are effective in the general population are not
context. For instance, epidemiological research has always as effective for those with mental illness. Separation
applied syndemic frame­works to characterise the complex of patients into diagnostic categories (eg, depression,
relationships between poverty, diabetes, mental illness, anxiety, and schizophrenia) is not an effective way of
and infectious diseases in low-income settings.178 This determining the best primary prevention strategies for
syndemic approach highlights that national and local physical health. Instead, transdiagnostic approaches that
conditions affect the interplay between physical and account for individual-level differences (eg, gender, cultural
mental health, and shows the importance of taking social, and ethnic identity, lifestyle risk factors, medication use, and
political, and economic factors into account when social circumstances) will be more effective (see Part 2).
designing public health interventions, or implementing
changes to health services (table 4).179 Secondary prevention
Numerous national and international health-care and Secondary preventive strategies, such as screening and
advisory bodies are now focusing on health inequalities preventive treatments, are often underused in people with
in people with mental illnesses. Resources from these mental illness.216–218,222 Many people with mental illness are
organisations (table 5, appendix pp 35–42) present new affected by comorbid physical diseases, which can be present
ideas and best practice approaches for improving the from illness onset (see Part 1). Population-scale data from
integration of physical and mental health care at the NHS England390 indicate that physical health intervention is
individual, health service, and societal levels. Several required even from childhood for those with mental illness. At
key health organisation guidelines149,330,386 and academic the age of 11–19 years, children with mental illness are three
articles179 have included case studies of new local and times as likely to be obese as children without mental illness.
national initiatives that account for the surrounding Tertiary prevention
environmental conditions and improve the integration of Tertiary preventive strategies involve improving treatment
physical and mental health care. As well as detailing and recovery from disease. To be engaging and responsive,
required improvements to health care for existing integrated care services require flexibility from individual
patients, some sets of guidelines discuss approaches to clinicians and service planners. For example, cardiac mortality
prevention of chronic physical and mental health among patients with severe mental illness is significantly
conditions.330,386 Wide-scale adoption and implemen­tation reduced by efficient administration of cardioprotective
of strategies that aim to prevent chronic conditions medications after first cardiac events.227 This supports the
(physical or mental), multimorbidity, and risk of claim made in new guidelines328,387 that tertiary preventive
premature mortality are required to reduce health measures for people with mental illness are underused,
inequalities for patients with mental illness in the future. despite their potential to improve health and reduce
Some examples and considerations for prevention at the premature mortality.
primary, secondary, and tertiary levels are presented in
panel 6.
present to the health system through primary care, and
Improving integrated care for people with mental illness most mental health care is delivered in primary care.179
Effective management of multimorbidity requires Patients requiring specialist mental health services still
integrated care to be provided in a holistic manner,391 so need ongoing engagement with primary care to deliver
that common risk factors and the bidirectional interaction and coordinate other aspects of their health care,
between physical and mental health disorders, and the including prevention and management of comorbid
treatments for each, can be addressed together.386 physical illness. The aim of primary care is to provide
Internationally, health organisations agree that primary equitable, accessible, safe, effective, comprehensive,
care is the optimal setting for addressing and person-centred care that meets the needs of individuals,
coordinating the management of multimorbity.392,393 In families, and communities throughout life.394 Therefore,
many countries, most people with mental illness first primary care is ideal for managing multimorbidity,

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Health system

Access to evidence-based lifestyle Self-management and screening

interventions on referral from health Patient strategies for physical health risk
professionals factors

Implementation and
Access to digital health technology Multimorbidity awareness, and education
guidance of a collaborative Health
(eg, text messaging, smartphone of health professionals, patients,
model for all patients with professionals
applications) and carers
long-term conditions

Liaison psychiatry services in general hospitals

and non-mental health outpatient services,
particularly in clinical areas with a higher
prevalence of mental illness
Carers

Multimorbidity awareness campaigns to improve access to self-monitoring of health

Protected hours for Shared budget for liaison Development of national Sharing of medical records Telepsychiatry and Continuity-of-care
interdisciplinary meetings psychiatry services from guidelines that consider between clinical telemedicine for case programmes at hospital
to supervise case mental health and multimorbidity, regardless professionals from supervision discharge for both mental
management non-mental health services of the direct relationship mental health and and non-mental illnesses
with mental health non-mental health services
outcomes

Figure 3: Proposed model of collaborative care for people with physical and mental comorbidities

which requires an individualised approach that not only (appendix p 35). Some examples of integrated care
addresses the increased burden of multimorbidity, but models, and their evaluated outcomes, are described in
also manages competing or conflicting treatment needs panel 7.
by accounting for individual preferences and treatment
priorities.392 Further discussion on how primary care Managing substance comorbidity and promoting
settings should provide physical health care for people smoking cessation
with mental illness is presented in the 2018 guidelines Across many mental illnesses, the use of alcohol,
from NHS England387 (appendix p 38). tobacco, and illicit drugs is more prevalent than in the
As a minimum level of integration, health providers general population, and is associated with worse physical
should communicate with each other frequently to ensure and mental health outcomes (table 2).405–407 A bidirectional
the safety and effectiveness of treatment. Ideally, services relationship exists between substance misuse and
should take further steps towards integration, aiming for mental illnesses, because substance misuse can cause
multidisciplinary care that is structured, comprehensive, and exacerbate mental illness, yet it is often used by
and proactive. However, integration of this type usually patients as a way of reducing anxiety, dysphoria, and
involves overcoming bureaucratic barriers at the service other symptoms.408 Genetic risk factors for schizophrenia
level, such as difficulties in sharing medical records. also appear to predispose individuals towards illicit drug
Governance and funding issues can also restrict the use.409
provision of coordinated health care (figure 3). A 2016 Addressing substance misuse within mental health
report386 from the King’s Fund in the UK presents an services should be a high priority.408 However, many
aspirational approach towards improving integrated care services have no standardised screening for substance
across a range of physical and mental health conditions, use, and mental health clinicians are often not trained
with advice on overcoming common barriers to to treat substance misuse.410 For example, in high-
implementation. For instance, the report recommends a income countries, people with severe mental illness
curriculum redesign to give all health professionals a report wanting to quit smoking as much as the general
common foundation in mental and physical health and population, but are unlikely to be supported to do
encourage a whole-person approach, and creating so.331,332 Furthermore, patients are sometimes excluded
opportunities for skills transfer between professionals from drug treatment programmes or mental health

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services if they have comorbid drug or alcohol use

disorder.411 Panel 7: Examples of integrated care for physical and mental illness
Because of the complexity of comorbid mental health Within the broad category of integrated care, collaborative care models are emerging as
and substance use disorders, patients need individualised effective approaches that can simultaneously reduce costs and improve clinical outcomes
treatment that has an emphasis on overcoming the and treatment adherence in the management of both mental illness and chronic physical
barriers associated with mental illness and enhancing conditions.395–398 A core component of collaborative care models is the involvement of
engagement with evidence-based treat­ments. Readiness several health-care professionals working as a team, including a physician, a case
for change, cognitive ability, and cognitive distortions manager, and a mental health clinician.395,396 Although the specific actions vary between
resulting from mental illness need to be taken into models, all collaborative care approaches use structured management plans, scheduled
account. Evidence-based treatments include motivational patient follow-ups, and extensive interprofessional communication.395 Figure 3 shows the
interviewing, cognitive behavioural therapy, and family potential components of a collaborative care model for improving health management in
interventions (also known as family therapy).408 people with physical and mental comorbidities.
Evidence-based interventions can be a challenge to
The TEAMcare intervention399,400 in 14 primary care clinics in Washington, USA, is an
implement in mental health services that are already
example of a collaborative care approach within primary care. TEAMcare was designed for
struggling to meet demand. Notably, little evidence is
adults with depression plus diabetes, heart disease, or both, and comprised
available to recommend integrated interventions as
pharmacological care management with integrated behavioural change support delivered
compared with sequential or parallel treatment
by a nurse. Compared with usual care, the TEAMcare intervention resulted in significant
programmes, particularly in alcohol use disorders.412
improvements in metabolic health over 12 months, with a decrease in the percentage of
Each approach has advantages and disadvantages. One
glycated haemoglobin of –0·56% (95% CI –0·85 to –0·27), a decrease in LDL cholesterol of
advantage of an integrated approach is that the patient
–9·1 mg/dL (–17·5 to –0·8), and a decrease in systolic blood pressure of –3·4 mm Hg
does not need to receive care from two services, whereas a
(–6·9 to 0·1). A reduction in Symptom Checklist Depressive Scale score of more than 50%
disadvantage is that it requires substantial resources and
was found in more than three times as many patients in the TEAMcare group compared
investment from within the mental health system to train
with usual care (odds ratio 3·37, 95% CI 1·84 to 6·17), as well as improved perceived
mental health clinicians in the treatment of substance use
self-efficacy, and greater patient satisfaction with medical care.399–401
disorder. An advantage of sequential or parallel treatments
is that the interventions are delivered within a highly The COINCIDE trial397 tested a psychological intervention for people with depression and
specialised substance use programme. However, the comorbid diabetes or cardiovascular disease that addressed behavioural activation,
approach requires coordination and sharing of information healthy lifestyle, exercise, and diet. This integrated approach resulted in significant
between agencies. A clear referral policy between mental improvements in depression and patient satisfaction at 4 months.173 Health benefits were
health and substance misuse treatment services (including sustained at a 24-month follow-up, and the intervention was found to be
those in primary care) should be developed so that a cost-effective.173 Additionally, evidence from the RAINBOW trial, published in 2019,
programme of patient care is delivered consistently and in supports the use of collaborative care models for improving both physical and mental
full. health outcomes in people with common mental disorders and cardiometabolic
Regardless of how interventions are provided, comorbidities.402 However, these evaluations of collaborative care models have all been
investment in screening within mental health services is done in high-income settings; similar evaluations in low-income and middle-income
a priority. Mental health clinicians should be trained to do settings are needed (see Part 5).
regular assessments of comorbid substance use, to assess Although collaborative care models have been shown to be effective for people with
patients’ readiness for change, and to provide motivational common mental disorders, the evidence for their use in people with long-standing severe
interviewing. An emphasis on a so-called no wrong door mental illness is conflicting,174,403,404 and optimal models of integrated care in this group are
policy for accessing substance misuse treatments, in yet to be found. The PRIMROSE study174 compared integrated primary care with usual care
which everyone is accepted and offered treatment in 327 people with severe mental illness, and found no significant benefits for HDL
wherever they present, and the development of clear cholesterol over 12 months. However, integrated care did have a 12-month mean cost
referral policies between mental health and substance difference of –£824 (95% CI –568 to 1079) compared with usual care, and was found to
misuse treatment services should be a priority.330 be cost-effective because of fewer hospital readmissions over a 12-month period.174
If cessation of substance misuse is not possible, harm-
minimisation strategies should be adopted. For instance,
patients might be able to switch to alternative, safer Innovations in integration for low-income and
forms of the drug (eg, e-cigarettes, methadone, or middle-income countries
buprenorphine and naloxone) or access could be In most low-income and middle-income countries,
provided to safe injecting facilities. The challenges and less than 1% of the health budget is spent on mental
innovations regarding smoking cessation interventions health,414 including mental health care within specialist
for people with mental illness are presented in panel 4. mental health services, general health services, and
The Royal College of Physicians published a report in social care services.414 As a result, mental health services
2016 on harm minimisation for those who are unable or are poorly resourced; 90% of people who need treatment
find it difficult to quit, which recommended e-cigarettes, do not receive any care.415 Mental health services in low-
nicotine replace­ ment therapy, and other non-tobacco income and middle-income countries predominantly
nicotine products.413 rely on expensive psychotropic drugs, which are seldom

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available, and are associated with various side-effects required, with rolling programmes to support staff
that require close management (see Part 3).416 Previously, turnover.420 In addition, mental health policies in low-
little attention has been given to the complex income and middle-income countries need to be changed
bidirectional relationship between physical and mental to make an integrated care model the central focus of
health, and the relevance of screening, in low-income mental health care action plans. A review across high-
and middle-income settings.416,417 income, middle-income, and lower-income settings179
WHO guidelines from 2018 state that health inequalities presents clear evidence for the rationale and effectiveness
for people with severe mental illness could be worse of integrated care. The Practical Approach to Care Kit
in low-income and middle-income countries than (PACK), which comprises a guide, a training strategy, a
high-income countries, because “the resources are health system strengthening intervention, and
inadequate, the institutions are not well managed and monitoring and evaluation, is an example of a best-
access to quality mental health care and physical care is practice approach towards providing universal integrated
limited”.328 The largest gaps in life expectancy for people primary health care.421 PACK has been successfully
with severe mental illness compared with the general implemented in several low-income and middle-income
population are observed in low-income settings.5,149 countries, including Botswana, Brazil, Ethiopia, Nigeria,
Mental health care systems in low-income and middle- and South Africa.422 Development of clinical practice
income countries need to be reoriented towards guidelines that build on best-practice examples such as
integrated models. However, many low-income and PACK and consider the local context, including staff
middle-income countries do not have integrated physical attitudes and available resources, will be crucial in
health and mental health services, and have poorly encouraging policy uptake in low-income and middle-
developed community-based services, resulting in over- income countries. The local context, including prevalent
reliance on institutional psychiatric care.416 In many knowledge, behaviours, and attitudes towards mental
countries, mental health legislation and policies are health conditions, is a good predictor for the success of
outdated.417 Specific barriers to the development and implementing changes to clinical practice.420
implementation of integrated mental and physical health Clinical practice guidelines should also incorporate
policies include: insufficient coordination across different strategies for collaboration between formal primary care
government levels; a shortage of trained staff at all levels and mental health services, and community-based
of care; a need for commitment from health services; providers, such as traditional healers. Approximately half
governmental bureaucracy; and shortage of funding. In of individuals seeking formal health care for mental
addition, funding for health services is provided by disorders in low-income and middle-income countries
several different sources, which makes the sharing of choose traditional and religious healers as their first care
decisions and responsibility challenging.179 As a con­ provider, and this choice is associated with delays in
sequence, in daily clinical practice, mental health accessing formal mental health services.423 Based on
providers in community settings do not generally ask research into collaboration between traditional healer
about or test for physical health issues because they are and biomedical health systems in Uganda,424 strategies
not considered to be a priority, and time and resources are should involve improving clinicians’ understanding of
limited.418 traditional healers’ explanatory models for illness, and
In low-income and middle-income countries, there is vice versa. Trust between the two types of health-care
an urgent need to increase awareness that patients with providers needs to be improved so that they can interact,
mental health illness could have physical health needs, rather than operating in isolation. In particular, negative
and vice versa.416 For example, public health campaigns attitudes of clinicians towards traditional healers need to
could increase awareness of the links between chronic be addressed. The quality of care provided by traditional
physical and mental disorders. In a 2016 review419 of healers needs to be enhanced by improving hygiene
interventions for mental disorders at the population and practices and eliminating unethical practices.
community levels in low-income and middle-income Task sharing with key community-based providers is a
countries, mass public awareness campaigns and school- potentially effective implementation strategy in low-
based awareness programmes were considered to be resource settings. Task sharing is the process of trans­
good practice, with limited but promising evidence to ferring a task usually delivered by a scarce resource, such
support their use. as a physician, to a rapidly trained and less scarce
At the system level, the physical health of people with resource, such as a health-care worker.425,426 Research on
mental illness could be improved by increasing the the implementation of task-sharing collaborative-care
competencies of existing staff at all levels of care. models is being done,427–429 and the findings could improve
Although education campaigns on the links between our understanding of the quality, safety, effectiveness,
chronic physical and mental health conditions are and acceptability of such strategies for mental health
important tools, bringing about changes to skills and disorders in low-income and middle-income countries.
behaviour will require a long-term approach. Multiple Case studies from non-governmental organisations show
training sessions and subsequent top-ups will usually be that inefficient health system structures can present

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barriers to successful task sharing,427 indicating a need for food item, and recommends healthier alternatives from a
more collaborative care services. However, whether such crowd-sourced database of nutritional information.440
approaches will be successful in reducing premature Several smartphone functionalities could be valuable
mortality, improving wellbeing, and achieving better for improving health, including the recording and
social outcomes in low-income and middle-income analysis of data from sensors measuring activity or
settings has yet to be fully established.427 biological variables; access to health information via the
internet; and the ability to engage with social media
Digital technologies for people with mental illness campaigns on lifestyle change.441 Increasingly, people can
Digital technology plays an increasing role in promoting access elements of their electronic health records via
health, addressing risk factors, and managing physical their smartphone or other portable device, providing an
disease, with growing evidence for its effectiveness. important opportunity for partnership between patients
Mobile phones provide a particularly convenient and health professionals, and for empowerment of
platform for digital health-care delivery (also known as patients to be more involved in decisions about their
mHealth). WHO estimates that 95% of the global health care. However, because smartphones are more
population lives in an area covered by mobile networks, expensive than basic mobile phones and require an
and over 7 billion mobile contracts have been issued, internet or data connection, text messaging might be
which is one for almost every person on the planet.430 required to reach the wider population in some low-
Smartphone technologies are closing the so-called income settings.442
digital divide (ie, between those who have easy access to To date, most studies using mHealth to promote
computers and the internet, and those who do not) that healthy behaviours have recruited from the general
was previously present in low-income and middle- population. Increasing numbers of individuals with
income countries.431 Unlike traditional health services severe mental illness also want to use technology to
that require attendance at a specific time and location, manage their health.443 Although few evaluations of
digital technology is available at a time and place that mHealth for physical health in mental illness have been
suits the patient. done, emerging evidence indicates that online peer-
Technologies as simple as text messaging have been support platforms, smartphone apps, and fitness trackers
shown to support lifestyle improvement. For example, in can successfully increase walking and physical activity in
the TEXT ME trial of 710 patients with coronary heart people with severe mental illness.381,444,445 Furthermore, a
disease,432 patients in the intervention group received review of digital health technologies for people with
four personalised text messages per week for 6 months depression446 found that online lifestyle interventions can
that provided advice, motivation, and support to change have positive effects on various health behaviours,
lifestyle behaviours. After 6 months, levels of LDL including alcohol use, sleep, and physical activity.
cholesterol were significantly lower in intervention Although the evidence is only preliminary, mHealth is a
participants compared with patients who received usual promising route towards reducing physical health
care, with concurrent reductions in systolic blood disparities for people with mental illness globally, and
pressure and body-mass index, significant increases in further research is warranted (figure 1). Widespread
physical activity, and a significant reduction in self- adoption of mHealth will depend not only on technological
reported smoking. Further studies to assess the advances, but also on rigorous evaluation of digital health
sustainability of these positive changes, and the effective­ interventions and overcoming of common limitations,
ness of text messaging in participants who have not yet such as consumer perceptions (particularly around safety,
experienced a cardiovascular event, are underway.433 Text reliability, and trustworthiness) and ethical risks, such as
messaging can also support other important health the potential for intrusion, coercion, and data privacy
behaviours, such as medication adherence for people breaches.408,447
with chronic conditions.434
Smartphone apps might promote healthy lifestyle Who is responsible?
change, but they vary in quality, and the quality of To turn ideas into actions, governments, health
reported evaluation research is also inconsistent.435 To commissioners, and care providers must acknowledge
date, few studies have examined clinical effectiveness or their respective responsibilities for improving physical
cost-effectiveness.436 In addition, user engagement could health for people with mental illness, and clear
be lower in everyday clinical practice than in trial accountabilities must be established. For instance,
settings.437,438 Key strategies for effective user engagement primary prevention is often regarded as the duty of
include designing interventions in collaboration with governments, rather than health services.448 The increased
patients, personalisation of interventions, and just-in- risk for physical disease among people with mental
time adaptation (in which an intervention supports an illness, which can be present even before the
individual's changing behaviours and contexts over first diagnosis of mental illness, could represent a failure
time).439 An example is the Australian FoodSwitch app, at the public health level, and perhaps even wilful
which uses a smartphone camera to scan the barcode of a abandonment of educational and health promotion

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initiatives to reach this marginalised group. However, mental comorbidities (see panel 2). This economic
socioenvironmental factors that contribute to poor burden must also be considered alongside the unresolved
physical health, such as a shortage of green spaces and (and worsening3,21–23) personal burden of comorbid
walking routes, the affordability and accessibility of fast physical diseases that disproportionately affect people
foods compared with healthy foods, and tobacco and with mental illness across the entire life course.
alcohol advertising (and associated legislation), are all Substantial research investment in this area is now
areas that could feasibly be targeted by local and national required to eliminate physical health inequalities, and to
health policy to improve the physical health of people develop novel methods that will prevent these disparities
with mental illness. from arising in future generations.
Furthermore, increasing evidence suggests that
obesity,449,450 smoking,451,452 and physical inactivity453,454 are Conclusion
dual risk factors for both chronic physical conditions and Large disparities in physical health for those with mental
mental illnesses. Because these risk factors are also illness are an ongoing health issue, and might even be
associated with social deprivation,182,455 greater investment worsening in some regions. Although this inequity is
in public health schemes and policy to proactively address increasingly gaining attention, further investment,
them in at-risk groups, particularly in young people, intervention, and research are urgently required to
could potentially reduce the incidence of both physical address the premature mortality and lifelong burden of
and mental illnesses. However, the effectiveness of such poor physical health associated with mental illness.
schemes has yet to be demonstrated, and should be Nonetheless, our Commission takes an optimistic
considered a promising area for future research (figure 1). approach, and describes how disparities could be
The risk of physical disease in people with mental reduced through evidence-based prescribing and better
illness is further compounded by barriers to health care integration of physical and mental health care. Our
at the personal, service, and social levels for this priority actions for health policy, clinical services, and
population. As a priority action, governments must future research are presented in figure 1. Promisingly,
address the inequalities in health insurance and access to multiple national and international guidelines now
care for people with mental illness, to provide a suitable present feasible actions for improving the integration of
environment for effective medical and lifestyle inter­ physical and mental health, across various health and
ventions. Additionally, health commissioners must social care settings. Broader implementation of lifestyle
acknowledge the shortage of resources allocated to the inter­
ventions for mental illness is also required to
protection of cardiometabolic health in mental health reduce elevated cardiometabolic risk and attenuate
services, and the broad neglect of physical health risks in medication side-effects. Whenever possible, inter­
the treatment of mental illness. ventions should maintain the core principles of
Clinical staff should also reflect on the duty of care that evidence-based lifestyle programmes (such as the DPP)
they have to people with mental illness, both at an and be made accessible to those who do not have current
individual level and through their national associations. physical comorbidities, with the aim of protecting
Given the foreseeable nature of poor physical health cardiometabolic health from the earliest stages of
outcomes, protecting the physical health of people mental health treatment. From a public health
receiving treatment for mental illness should be regarded perspective, further exploration of population-scale
as within the scope of clinical duty of care. Within strategies for primary prevention of co-occurring
sufficiently resourced settings, this duty of care must physical and mental disorders is warranted. Additionally,
include: (1) measuring and addressing the physical more government action is required to prevent
health of the patient; (2) clearly explaining the risks discrimination and ensure equitable access to all aspects
associated with treatment; and (3) taking appropriate of health care for those with mental illness. Overall,
action to mitigate those risks and protect the physical protecting the physical health of people with mental
health of the patient. As demonstrated in this illness should be considered an international priority
Commission, and evidenced in guidelines (appendix pp for reducing the personal, social, and economic burden
35–42), good clinical practice in mental health care is of mental health conditions.
increasingly considered to include monitoring the Contributors
physical health of service users. The Commission consisted of five independent parts to which authors
The allocation of research funding is another pathway were assigned as lead authors or co-authors. NS was the lead author
for Part 1. AK was the lead author for Part 2. DSi was the lead author for
through which systemic discrimination affects the health Part 3. SR was the lead author for Part 4. CG was the lead author for
and wellbeing of people with mental illness. Major Part 5. Co-authors for each part are detailed in the appendix, and all
research councils must aim to provide more funding to authors contributed equally to the writing of their respective sections.
address the physical health disparities that affect people All authors have approved the final versions.
with mental illness. As a solely economic justification, Declaration of interests
the allocation of resources should at least correspond CUC reports personal fees from Alkermes, Allergan, Angelini,
Boehringer Ingelheim, Bristol-Myers Squibb, Gerson Lehrman
with the demonstrated financial cost of physical and

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