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Cognitive Functioning, Physical Health and Early Non-response in Schizophrenia
Shifting Perceptions in Safety Issues Figure 13: Shifting Perceptions Regarding the
with Antipsychotics
Safety of Antipsychotics
Early safety concerns regarding antipsychotic medications focused on
risk of movement disorders, including tardive dyskinesia. Medical and
Past Present
specifically ‘cardiac’ considerations centred largely around the risk of Torsades de
drug-induced QTc prolongation and the associated potential for
pointes
QTc
Diabetes
cardiac arrhythmias that could lead to sudden death. Individuals at
Long
increased risk of sudden death due to prolongation of the ventricle
QT
Weight
gain
Raised
depolarisation–repolarisation interval include those who have a family
glucose
CHD
history of congenital long QT syndrome (>500msec) or those who are Weight
Insulin
using drugs that markedly increase QTc (>60msec). However, this risk
gain Insulin
resistance
resistance
Hyper-
must be understood in the context of broader cardiovascular
lipidaemia
QT
Hyperlipidaemia
Raised CHD
considerations, including coronary heart disease, the leading cause of glucose
death in developed countries. Unlike risks such as obesity and
dyslipidaemia, epidemiological studies have shown that modest
prolongations of the QTc interval are not a risk factor for cardiovascular
Concerns regarding the safety of antipsychotics no longer centre around QT prolongation,
but have shifted towards the effects of antipsychotics on key modifiable risk factors for
disease mortality or sudden death.
84
Moreover, the QTc interval is highly cardiovascular disease (CVD).
variable both between and within individuals.
85
Although there is no
definitive limit for what qualifies as a ‘normal’ QTc, an ad hoc expert
group has suggested cut-off points of >450msec in males and
Table 3: Benefits of Reducing Key Modifiable Risks of
Cardiovascular Disease
>470msec in females as prolonged.
86
Risk of arrhythmic events such as
torsade de pointes becomes a consideration if the QTc exceeds
Risk Factor Intervention Outcome
500msec in the presence of clinically relevant risk factors.
85,87
Notably,
Cigarette smoking Smoking cessation Decrease risk of CHD by at
there are no currently used antipsychotic agents that produce mean
least 50%
1
increases in QT interval analogous to the >30–50msec increases that
High blood pressure Decrease diastolic Decrease risk of CHD by
would routinely present a potential for inducing arrhythmias in normal
pressure by ~6mmHg 16%, MI by 14%, stroke by
populations. Therefore, in summary modest prolongations of QT are not 42%
1
a risk factor for cardiovascular disease mortality or sudden death that is Blood cholesterol 10% decrease Decrease risk of CHD by
similar to the well-established risk factors of obesity, dyslipidaemia,
30%
1
diabetes, hypertension, physical inactivity or cigarette smoking. The
Weight gain/inactivity Maintain ideal body Decrease risk of CHD and
current evidence regarding the relative risk of QT prolongation has
weight/active lifestyle MI by 35–55%
2,3
resulted in a shift in overall perception regarding the safety of
CHD = coronary heart disease; MI = myocardial infarction. Adapted from Hennekens, 1998,
Rich-Edwards et al., 1995 and Bassuk and Manson, 2005.
97–99
antipsychotic agents, increasing focus on the key modifiable risk factors
for CVD and related conditions such as obesity and dyslipidaemia that
can be influenced by antipsychotic treatment (see Figure 13). A consensus statement recently issued by the EASD, the European
Society of Cardiology (ESC) and the European Psychiatric Association
Underutilisation of Established (EPA) advocates close monitoring for individuals in this high-risk
Prevention Approaches population.
93,94
This statement addresses the concerns regarding CVD
Despite a growing focus on CVD, related conditions and the and diabetes prevention in individuals with severe mental illness and
corresponding risk factors, these elements remain largely outlines how current European CVD prevention and diabetes
underdetected, underdiagnosed and undertreated in patients with guidelines can be optimised in these patients and how these ideas, as
mental illness.
60,88–91
Screening for hyperglycaemia and dyslipidaemia well as CVD risk assessment, can be implemented by psychiatrists in
generally occurs rarely in those with serious mental disorders. A routine practice. Although the risk factors contributing to increased
cohort study with 55,436 patients found that in the four months prior morbidity and mortality in this patient population are recognised, there
to and following a new antipsychotic prescription, fewer than is still a need to further increase awareness about adequate screening
one-third of patients had their plasma glucose levels measured, while and monitoring of this high-risk population. Recent evidence shows
<10% had their plasma lipid levels measured.
63
Patients with that clinicians have been slow to adopt the screening and monitoring
concomitant CVD are less likely to receive cardiac therapies of proven approaches recommended by numerous associations, including the
benefit,
88
and this trend is similar for mentally ill patients with ADA, APA and US Food and Drug Administration (FDA); limited
diabetes. A large study of patients with diabetes found that the improvement has been observed in the rates of glucose and lipid
presence of mental illness significantly reduced the likelihood of screening and monitoring between the periods before and after the
receiving appropriate monitoring of eye care, plasma lipids and recommendations were issued, suggesting that patients with mental
glycated haemoglobin levels.
90
This lack of adequate therapy illnesses are continuing to receive sub-optimal healthcare.
95,96
It is
and attention is further emphasised in baseline data from the indeed a lost opportunity for these patients to go untreated; even
CATIE study in which a vast majority of the patients enrolled were minute reductions in any of the key modifiable risk factors may lead to
not being treated for co-morbid conditions: 88% of patients beneficial effects (see Table 3).
97–99
with dyslipidaemia were not receiving any lipid-lowering
pharmacotherapy; 62% of those with hypertension were receiving no Summary
antihypertensive medications; and 30% of those with diabetes were Morbidity and mortality rates are much higher for those with
not undergoing antihyperglycaemic therapy.
92
mental illnesses relative to the general population, largely related
EUROPEAN PSYCHIATRIC REVIEW 33