Cardio Metabolic Risk in Individuals Prescribed Long Acting - 2019 - Psychiatry
Cardio Metabolic Risk in Individuals Prescribed Long Acting - 2019 - Psychiatry
Cardio Metabolic Risk in Individuals Prescribed Long Acting - 2019 - Psychiatry
Psychiatry Research
journal homepage: www.elsevier.com/locate/psychres
A R T I C LE I N FO A B S T R A C T
Keywords: People living with severe mental illness (SMI) experience significant physical health co-morbidity. Few studies
Severe mental illness have focused on physical health outcomes for those prescribed long-acting injectable (LAI) antipsychotics. This
Physical health observational cross-sectional study aimed to assess the prevalence of metabolic syndrome (MetS) and other
Metabolic syndrome cardio-metabolic risk factors in a large cohort prescribed LAI and managed by community mental health ser-
vices. For participants with elevated cardio-metabolic risk factors, the proportion receiving appropriate man-
agement was assessed. Of the 301 eligible participants, many met the full criteria for MetS (44%) and its
components. Cardio-metabolic risk factors were largely under- or un-treated. Smoking rates were very high
(62%) along with reported high rates of physical inactivity and poor dietary intake. The vast majority (89%)
reported seeing their general practitioner in the preceding twelve months. Individuals prescribed LAI have a very
high prevalence of MetS and potentially modifiable risk factors for cardiovascular disease. Routine monitoring
accompanied by evidence-based treatment of cardiometabolic abnormalities which contribute to significant
morbidity, disability and premature death should be prioritised. Better collaboration between mental health
services and primary care providers should be pursued to optimise the delivery of effective physical health care
to individuals living with SMI.
1. Introduction with SMI including disparities in health care provision (Lawrence and
Kisely, 2010), positive and negative symptoms associated with SMI,
People experiencing severe mental illness (SMI) are likely to die diagnostic overshadowing (Leucht et al., 2007), lifestyle and socio-
12–15 years earlier than the general population, with the primary economic factors (Leucht et al., 2007) and particularly medication that
driver for this premature mortality being cardio-vascular disease (CVD) is prescribed to treat SMI such as antipsychotics (Newcomer, 2007).
(Correll et al., 2017; Lawrence et al., 2013). The poor physical health of Long acting injectables (LAI) offer an alternative to oral anti-
people with SMI is well recognised, with significantly higher rates of psychotic (AP) medications in the treatment of SMI including schizo-
smoking, type 2 diabetes (T2DM), CVD and metabolic syndrome (MetS) phrenia. LAI have been argued to have pharmacokinetic benefits
(De Hert et al., 2009; Lappin et al., 2018; Rummel-Kluge et al., 2010; compared to oral APs that enable the use of lower doses, and result in
Vancampfort et al., 2015b) than their general population peers. MetS is greater relapse prevention (Leucht et al., 2011; Spanarello and
a key measurable predictor for the development of both T2DM and CVD Ferla, 2014) however evidence of the extent they may impact cardio-
(Lakka et al., 2002). Individuals with MetS have 3–6 times increased metabolic outcomes is limited. A meta-analysis comparing 13 rando-
risk of mortality due to coronary heart disease and 5–6 times the risk of mised control trials (RCTs) of second-generation LAI and oral APs over
developing T2DM than people without (Alberti et al., 2009). MetS is a mean timeframe of 39 weeks found no significant differences in
identified by the comorbidities of abdominal fat distribution, insulin weight gain, suggesting that metabolic effects may be independent of
and lipid irregularities and hypertension (Alberti et al., 2009). There the route of administration (Fusar-Poli et al., 2013). Importantly,
are numerous contributors to these MetS components among people second-generation LAI were almost three times (RR = 2.75) more likely
⁎
Corresponding author: 26 Llandaff Street, Bondi Junction. NSW 2022 Australia.
E-mail address: [email protected] (R. Morell).
https://doi.org/10.1016/j.psychres.2019.112606
Received 22 July 2019; Received in revised form 8 October 2019; Accepted 8 October 2019
Available online 09 October 2019
0165-1781/ © 2019 Elsevier B.V. All rights reserved.
R. Morell, et al. Psychiatry Research 281 (2019) 112606
to lead to weight gain than placebo, highlighting that metabolic effects (FGA) or second- (atypical) (SGA) generation on the basis of dopamine
are a crucial issue to consider when prescribing APs (Fusar-Poli et al., D-1, D-2
and serotonin2 pKi values (Meltzer et al., 1989).
2013). Other metabolic markers, including glucose and lipid levels have
been compared in only a small number of studies comparing oral APs to 2.5. Anthropometry
LAI antipsychotic medications, none of which have demonstrated dif-
ferences according to route of administration in trials of between 24 Anthropometric data including height, weight, Body Mass Index
weeks and two years (Detke et al., 2014; Ishigooka et al., 2015; (BMI), blood pressure and waist circumference was collected using
McDonnell et al., 2011). Important caveats in considering the evidence standardised procedures. Participants were weighed without shoes and
from meta-analysis of RCTs is that they report on evidence in the early wearing light clothing on the OMRON HN-283 digital scale to the
stages of AP treatment, and often exclude individuals with common nearest 0.1 kg. Height was measured with shoes off, using a wall-
comorbidities. A more recent cross-sectional analysis found no sig- mounted stadiometer to the nearest 0.1 cm. BMI was calculated as
nificant difference in rates of MetS when comparing 151 day clinic weight (kg)/height (m)2 with participants characterised as normal
patients on oral and LAI APs (Ventriglio et al., 2018) and another small weight (18.5–24.9 kg/m2), overweight (25–29.9 kg/m2), obese
study of 130 outpatients on LAI described the cohorts MetS to be higher (30–39.9 kg/m2) and morbidly obese (≥40 kg/m2) according to WHO
when compared to more broad Spanish studies for people with Schi- criteria (World Health Organization, 1995). Blood pressure was mea-
zophrenia, Schizoaffective disorders or a severe mental disorder in- sured on the left arm in a seated position using an OMRON automatic
cluding major depressive disorder (Sanchez-Martinez et al., 2018). To sphygmomanometer. Waist circumference was measured horizontally
date, to our knowledge, there have been no comprehensive studies of at the navel at the end of expiration to the nearest 0.1 cm. Waist cir-
metabolic risk factors associated with LAI treatment in large samples cumference was categorised as ‘at risk’ according to International Dia-
ascertained in routine clinical settings. betes Federation (IDF) criteria for Europids (≥80 cm for females and
Given the chronic poor physical health experienced by people living ≥94 cm for males) (Alberti et al., 2006) with ethnic specific values of
with SMI, physical health outcomes for those prescribed LAI need to be ≥80 cm for Asian women and ≥90 cm for Asian men.
better understood. The aim of this study was to comprehensively assess
the prevalence of MetS and other cardio-metabolic risk factors in a large 2.6. Biochemistry
cohort of individuals with SMI prescribed LAI antipsychotic medication.
Metabolic blood measures were obtained via pathology services
2. Method within 6 months of the interview and included fasting blood glucose,
total cholesterol, triglycerides, LDL cholesterol and HDL cholesterol.
2.1. Study design and setting
2.7. Metabolic syndrome and risk for type 2 diabetes
This cross-sectional study was completed across three hospital sites
within the South Eastern Sydney Local Health District (SESLHD), All participants were screened for the presence of metabolic syn-
Australia, between October 2016 and December 2017. Assessments drome using the IDF definition criteria (Alberti et al., 2006):
were provided as part of routine clinical care, and therefore written Central Obesity, defined according to IDF criteria as outlined above.
consent was not obtained. Assessments were conducted either on-site at Plus two of the following four factors:
the hospitals, community centres or at the participant's home. This
study was deemed a quality improvement or quality assurance project 1 Serum triglycerides ≥1.7 mmol/L or receiving drug treatment for
by the SESLHD Human Research Ethics Committee HREC (17/298 this lipid abnormality
(LNR/17/POWH/580)) and has been carried out in accordance with 2 Serum high-density lipoprotein (HDL) cholesterol <1.03 mmol/L in
The Code of Ethics of the World Medical Association (Declaration of men and <1.29 mmol/L in women, or receiving drug treatment for
Helsinki) for experiments involving humans. this lipid abnormality
3 Systolic blood pressure ≥130 mmHg, diastolic blood pressure
2.2. Participants ≥85 mmHg, or treatment of previously diagnosed hypertension
4 Fasting plasma glucose (FPG) ≥5.6 mmol/L or previously diagnosed
Participants were people prescribed LAI and linked with community type 2 diabetes
mental health services across the three hospital sites in SESLHD for the
administration of the LAI. Risk for Type 2 Diabetes: The AUSDRISK questionnaire is a vali-
dated tool for identification of Australian adults at high risk of devel-
2.3. Outcome measures oping T2DM in the next five years (Chen et al., 2010). Participants had
waist measurement recorded and completed nine questions related to
Cardiometabolic risk measures were obtained during a face-to-face demographic characteristics, family history of diabetes, history of high
interview with participants who were also asked to rate their interest in blood sugar, smoking, diet, high blood pressure, physical activity,
interventions addressing smoking cessation, poor diet, and low physical ethnicity, and Aboriginal and Torres Strait Islander heritage. Scores
activity. were categorised as follows:
2.4. Socio-demographic and treatment details - low risk (5 or less) [approximately one person in every 100 will
develop diabetes]
Participant's socio-demographic and medication details including - intermediate risk (6–11) [6–8: approximately one person in every 50
sex, age, country of birth, psychiatric diagnosis, whether LAI was pre- will develop diabetes; 9–11: approximately one person in every 30]
scribed under an involuntary community treatment order (CTO), psy- - high risk (12+) [12–15: approximately one person in every 14 will
chotropic medication prescription, and prescription of medication for develop diabetes; 16–19: approximately one person in every 7; 20
glucose, lipid and blood pressure dysregulation, were obtained directly and above: approximately one person in every 3]
from participants or from their medical file. Defined Daily Dose
(McClave et al., 2010) (DDD) of all LAI antipsychotic medications ad- 2.8. Lifestyle components (smoking, physical activity and dietary intake)
ministered was calculated according to WHO standardised guidelines
(Leucht et al., 2016). Antipsychotics were classified as first– (typical) Nicotine dependence was measured using the Fagerström Test for
2
R. Morell, et al. Psychiatry Research 281 (2019) 112606
3. Results
survey. There were no significant differences in age (p = 0.39), gender
(p = 0.40) or diagnosis (p = 0.70). Proportionately more received their
Eligible participants (n = 517) were identified from medical records
LAI from a GP (n = 53, 25.1%) or at a home visit (n = 31, 14.7%)
at each of the community health centres. Of these, 301 (57.4%) com-
(p<0.0001) among non-completers. There was no significant difference
pleted a survey administered by mental health clinicians to elicit the
in the proportion of individuals on a CTO in both groups (p = 0.29).
physical health parameters.
3
R. Morell, et al. Psychiatry Research 281 (2019) 112606
Variables entered into a logistic regression analysis were (Table 3): Table 3
age >44years (χ2 = 6.42, p = 0.01), DDD >1 mg (χ2 = 2.15, Logistic regression model of metabolic syndrome on a priori variables of in-
p = 0.14), first or second generation LAI antipsychotic (χ2 = 2.67, terest.
p = 0.10), antipsychotic polypharmacy (χ2 = 1.71, p = 0.19) and pre-
Independent variable Odds ratio 95% ± CIa P
scription of a mood stabiliser and/or antidepressant (χ2 = 3.90,
p = 0.05). Only greater age was found to be a significant predictor of Age > 44 years 2.04 (1.12–3.71) 0.02
MetS (Exp(B) = 2.04, 95%CI 1.12–3.71, p = 0.02). DDDb > 1mg 1.59 (0.87–2.91) 0.13
LAI antipsychotic generation 1.42 (0.77–2.60) 0.26
Antipsychotic polypharmacy 0.65 (0.35–1.20) 0.17
4. Discussion
Mood stabiliser and/or antidepressant 1.62 (0.85–3.09) 0.14
prescription
Metabolic syndrome and multiple cardio-metabolic risk factors, in-
cluding smoking, poor diet and a predominantly sedentary lifestyle, Bold indicates significance at P < 0.05.
a
were highly prevalent in this large cohort of community-based in- Odds ratios and 95% Confidence Intervals for each variable as an in-
dividuals’ prescribed LAI antipsychotic medications. These findings are dependent predictor of metabolic syndrome.
b
Defined daily dose.
deeply concerning: the physical health of people with SMI in the care of
mental health services is very poor and predisposes them to premature
death. Only a minority of individuals received treatment for identified
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R. Morell, et al. Psychiatry Research 281 (2019) 112606
metabolic risk factors despite the majority having been seen by the clinicians to request testing and difficulties in completing testing by
mental health service and/or their GP in the prior three months. individuals experiencing SMI. Given the high GP attendance rates (90%
Finally, metabolic outcomes were equally poor among individuals within prior 12 months) it is possible that participants may have had
prescribed first- or second-generation LAI, consistent with previous pathology tests performed by the GP but these results were unavailable
evidence comparing metabolic side effects of oral typical and atypical to the mental health service and therefore this study. Those who refused
APs (Falissard et al., 2011). or did not participate in blood testing may have other markers making
MetS more likely (e.g. less engagement with health services or poor
4.1. Metabolic syndrome, smoking and polypharmacy health literacy) which could mean the study underestimated the true
prevalence of MetS.
Metabolic syndrome was present in 44% of those who had sufficient Among those with comprehensive metabolic monitoring completed,
measures to determine this, a rate almost double that of the general only a minority received any treatment for those metabolic abnormal-
population (Cameron et al., 2007). A recent prevalence study con- ities that were identified. Less than 15% of those with glucose levels
ducted in Spain of 130 outpatients prescribed LAI found that 46% of the raised to MetS at-risk levels received any treatment. Of those who re-
sample met the criteria for MetS (Sanchez-Martinez et al., 2018). These ceived glucose regulation treatment (predominantly metformin), over
high rates are comparable to those observed in individuals with SMI half were inadequately treated as evidenced by glucose levels which
prescribed clozapine (Lappin et al., 2018) and in other SMI populations remained above the at-risk threshold. Many (39%) of those with at-risk
(Galletly et al., 2012; Vancampfort et al., 2015a). Individuals younger levels of triglycerides were on no prescribed treatment and 50% of
than 35 years were approximately 2.5 times more likely to have MetS those on medication met at-risk thresholds even with the prescription of
than their age matched peers, as suggested by prevalence estimates in relevant medication. Similar deficiencies in treatment were found for
the general population (Cameron et al., 2007). This is consistent with irregularities in lipid profile and hypertension. Previous studies have
findings (Foley et al., 2013) that at-risk thresholds for cardio-metabolic found similarly common under-treatment for each of these metabolic
disease are met very early in people with psychosis, again highlighting abnormalities (Galletly et al., 2012). For the physical healthcare of
the need for early screening and intervention to prevent the onset and individuals with SMI to be prioritised it is imperative to move beyond
progression of CVD. A previous study comparing oral and LAI APs monitoring to provide evidence-based interventions.
found AP dose and “high risk” AP to be factors preliminarily associated Over 60% of clients had been in contact with their GP in the three
with MetS (Ventriglio et al., 2018) however, aside from older age months prior to this cross-sectional assessment and 90% had contact
(>44years), results did not indicate any other significant predictors for within the prior 12 months which is similar to attendance rates re-
MetS. Recent evidence among people with SMI shows that those with ported in national samples (Morgan et al., 2012) which also found that
MetS are three times more likely to relapse within one year in- 76% of GP visits were related to physical health. It is possible that those
dependently of potential cofounders (Godin et al., 2018) indicating the receiving LAIs from their GP may have physical health issues addressed
impact on both physical and mental health outcomes of untreated more frequently and diligently. As this cohort under represents clients
metabolic issues. that receive LAI from their GP, future studies could explore this idea.
Over 60% of participants smoked, in line with many previous stu- Regardless, multiple factors are likely to contribute to the finding of
dies showing the very high rates of smoking in SMI populations under-treatment of identified metabolic abnormalities, just as it has
(Cooper et al., 2012; Curtis et al., 2018; Galletly et al., 2012). Poly- been identified that multiple explanations contribute to the persistently
pharmacy was very common in the sample (36.2%), falling within high rates of smoking among people with SMI. For example, evidence
prevalence rates that vary between 10% and 50% internationally shows that people with SMI are less successful in their quit attempts
(Correll et al., 2008) and comparable to rates within Australians with (despite having comparable motivation to quit as smokers without
psychosis (Morgan et al., 2012). Many international guidelines mental health issues) (McClave et al., 2010). This under-treatment may
(APA(Lehman et al., 2004), NICE(National Institute for Health and Care be linked to cognitive deficits, self-efficacy and wider support networks:
Excellence, 2014)), though not all (RANZCP(Galletly et al., 2016)), do the same issues are likely to be relevant to the ability of people with
not recommend simultaneous prescription of more than one anti- SMI to seek, accept and or follow through on advice offered to improve
psychotic due to insufficient evidence to suggest it safely provides su- their physical health, including but not limited to adherence to phar-
perior treatment outcomes (Correll et al., 2008). In addition, and of macological treatments for metabolic irregularities. Despite the sig-
crucial importance, is the unknown impact polypharmacy has on me- nificant challenges, there is good evidence that people with SMI can
tabolic outcomes (Ijaz et al., 2018). make valuable improvements to their physical health through the up-
Physical inactivity (both low MVPA and high sedentary behaviour) take of lifestyle improvements such as increased physical activity and a
and a poor diet, characteristic of a high intake of energy dense, nutrient balanced diet (Daumit et al., 2013; Deenik et al., 2018).
poor processed foods, displacing core nutritious foods, were common in There is longstanding debate about where responsibility for the care
this population. Both are modifiable risk factors for cardio-metabolic of physical health conditions in people with SMI should lie. Lester
risk, and should be key targets for the prevention and management of (2006) argued that a collaborative approach is needed if there is to be
MetS, CVD and T2DM in people with SMI prescribed antipsychotic adequate development of high-quality healthcare for individuals with
medication (Teasdale et al., 2017). SMI (Lester and Gask, 2006). Suboptimal communication between
primary care and mental health services is likely to contribute to in-
4.2. Metabolic monitoring and treatment sufficient treatment and management of metabolic dysfunction
(Morgan et al., 2012). A large Australian study of recipients of re-
International (American Diabetes Association, 2004; De Hert et al., habilitation services found that despite high rates of metabolic mon-
2011; Shiers et al., 2014) and Australian (Curtis et al., 2012; itoring being completed there was inadequate sharing of results, and
Galletly et al., 2016) guidelines recommend routine monitoring for their implications, with recipients and/or with their primary health
metabolic dysfunction for individuals prescribed APs with schizo- care provider (Benson et al., 2018). The frequent attendance with both
phrenia and SMI more broadly. Monitoring of waist circumference in primary health care and mental health services as identified in this
this sample was completed for all patients as part of a lifestyle inter- cohort present valuable opportunities for regular review and treatment
vention, the Keeping Body in Mind program (Curtis et al., 2016), which of physical health issues holistically. LAI in particular provide this op-
is offered to them as part of routine clinical care. Less than half of in- portunity for physical health monitoring and treatment as they are
dividuals, however, had pathology blood tests conducted by the mental administered at regular intervals in a clinical setting, whether in pri-
health service in the prior 12 months, reflecting both a failure of mary care or a mental health service.
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